Hypocalcemia has been a common abnormality in the West, seen in patients admitted to the intensive care unit (ICU). It has also been linked with disease severity. We undertook this study to determine the frequency of hypocalcemia in patients admitted to the intensive care unit.In a retrospective chart review from January 2004 till December 2004, patients admitted to our ICU were reviewed. Patients’ age, sex, diagnosis, acute physiology and chronic health score APACHE II and ionized calcium were recorded. Patients were divided into three groups based on disease severity as measured by APACHE II. Hypocalcemia was defined as ionized Ca level less than 1.18 mmol/L. Frequency was determined in each group and correlation of hypocalcemia with disease severity was explored.P = 0.02).Hypocalcemia was seen in 22.2% in group A (APACHE II < 10), 40.4% in group B (APACHE II 10–19) and 53.9% in group C (APACHE II > 19). Hypocalcemia and disease severity (APACHE II scores) were negatively correlated , 1.19 mmol/L (±0.11) and 1.25 mmol/L (±0.24) respectively.Hypocalcemia is a common finding in critically ill patients. It is correlated with worsening disease severity. Mechanisms underlying hypocalcemia and the possible relationship of hypocalcemia with mortality need further consideration. Hypocalcemia is defined as a reduction in ionized serum calcium (Ca) concentration. In critically ill patients, it is a relatively common laboratory abnormality.–2 There The present study was intended to study the frequency of hypocalcemia in patients admitted to a Saudi intensive care unit and whether hypocalcemia has any correlation with disease severity measured by acute physiology and chronic health score APACHE II.Patients admitted to our ICU over a period of 1 year (Jan 2004–Dec 2004) were screened for inclusion criteria. Intensive care unit at King Abdulaziz National Guard Hospital is 10-bedded and caters to both medical and surgical. Patients admitted from either the emergency department or an operating room having had serum Ca measured within 24 h of admission were eligible for inclusion in the study. The corresponding day arterial blood gas was used for pH and ionized calcium levels. The APACHE II scores were also recorded during the first 24 h of admission. Patients with (1) hospital admission within 2 weeks before presentation (2) supplemental vitamin D therapy at the time of admission (3) known underlying chronic renal insufficiency defined as a creatinine level greater than 2.0 mg/dl (4) preexisting or known parathyroid disease (5) current treatment for malignancy (6) age less than 12 years (7) oral or iv calcium therapy and (8) any blood transfusion before Ca level was drawn were excluded. Three patient groups were defined based on APACHE II scores: group A, patients with APACHE II scores less than 10 (n = 50); group B, patients with APACHE II scores 10–19 (n = 85); and group C, patients with APACHE II scores more than 19 (n = 18). Thus, 153 patients were evaluated.Patient characteristics include age, sex, admitting diagnosis and preexistent chronic diseases. Parameters for patients included mean arterial pressure, presence of acute renal failure (ARF) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores at the time of ICU admission. Duration of ICU and hospital stay (days) was recorded as observational data.Laboratory data included values for total serum calcium (Ca), ionized serum Ca, magnesium (Mg), phosphate, creatinine, albumin and arterial pH. Calcium was analyzed with an ionic-specific electrode  using arterial blood sample. For analysis, pH 7.4 corrected values were used. Hypocalcemia was defined as an ionized Ca level less than 1.18 mmol/L. The normal range for our institution is 1.18–1.33 mmol/L.To determine frequency of hypocalcemia, patients were considered hypocalcemic if they had ionized Ca level less than 1.18 mmol/L at any time a measurement was available during admission to the ICU for all the groups. The frequency was compared among groups using chi-square test. In addition, absolute Ca levels among groups A, B and C were compared by averaging the multiple Ca levels per patient to arrive at a single value for each patient, namely, the average Ca level.Patient characteristics, length of ICU stay, serum magnesium, phosphorus and total calcium in groups A, B and C are shown in P = 0.02.Frequencies of hypocalcemia, based on ionized calcium, were 22.2% in group A, 40.4% in group B and 53.9% in group C. Frequency of hypocalcemia increased with increasing severity of disease based on APACHE II risk stratification model, which was statistically significant, with Group A patients had normal mean ionized Ca level of 1.22 mmol/L (±0.10). Among group B patients, the mean ionized Ca level was 1.19 mmol/L (±0.11). Group C patients had mean ionized Ca level of 1.25 mmol/L (±0.24).There was no correlation found, in our study, of levels of magnesium and phosphate with ionized calcium level.The mean APACHE II scores for groups A, B and C were 6.8 (±1.62), 13.1 (±2.56) and 23.5 (±3.85) respectively.We had seven deaths recorded in our cohort, one in group A and 3 each in group B and C. All ICU survivors were alive at the time of discharge or at the end of 30 days in hospital (whichever came first).et al. Due to smaller cohort, correlation of hypocalcemia with mortality could not be concluded. Moreover, magnesium and phosphorus levels did not correlate either with calcium or disease severity in our patients, which makes disease severity a more likely explanation for hypocalcemia.Results of our study show that hypocalcemia is very common in critically ill Saudi patients (as high as 54% in our cohort). Progressive decline in calcium levels with increasing disease severity as measured by APACHE II scores is in accordance with the data reported by Zivin Several mechanisms have been suggested for hypocalcemia in critically ill patients. These include pro-inflammatory cytokines in septic patients impairing PTH responsiveness,–10 catec14Correlation of hypocalcemia with mortality is far from proven. In one study, 30-day mortality was not predicted independently by hypocalcemia. It is moThis study is the first from the Kingdom to address frequency of hypocalcemia in Saudi intensive care population. Though in our patient population, there is a negative correlation of hypocalcemia with disease severity, this study is underpowered to detect any effect on short-term or long-term mortality. The cause of hypocalcemia in our cohort most likely seems to be due to several mechanisms . Prospective cohort studies need to be designed to explore the correlation of hypocalcemia with mortality. Moreover, markers of baseline vitamin D deficiency and PTH levels in Saudi patients of variable disease severity need to be studied to explore the possibility of widespread vitamin D deficiency.


This study was performed to assess the prevalence of dry eye syndrome and diabetic retinopathy (DR) in type 2 diabetic patients and their contributing factors.199 type 2 diabetic patients referred to Yazd Diabetes Research Center were consecutively selected. All Subjects were assessed by questionnaire about other diseases and drugs. Dry eye syndrome was assessed with Tear break up time tests and Schirmer. All the subjects underwent indirect ophthalmoscopy and retinal color photography. DR was graded according to early Treatment Diabetic Retinopathy (ETDRS) criteria.Of 199 subjects, 108 patients (54.3%) suffer from dry eye syndrome. Although dry eye syndrome was more common in older and female patients, this association was not significant. But there was significantly association between dry eye syndrome and duration of diabetes (P = 0.01). Dry eye syndrome was more frequent in diabetic patients with DR (P = 0.02). DR was found in 140 patients (70.35%), which included 34 patients (17.1%) with mild non proliferative DR (NPDR), 34 patients (17.1%) with moderate NPDR, 22 patients (11.1%) with severe NPDR and 25 patients (25.1%) with proliferative DR (PDR). There were significant relation between age, sex and duration of diabetes and DR.In this study the prevalence of dry eye syndrome was 54.3%. Diabetes and dry eyes appear to have a common association. Further studies need to be undertaken to establish an etiologic relationship. However, examination for dry eye should be an integral part of the assessment of diabetic eye disease. Diabetes is one of the most common leading causes of blindness in 20–74-year old persons . CataracAmong of diabetic patients referred to Yazd Diabetes Research Center, 200 type 2 diabetic patients, including new and review cases of diabetes (was diagnosed according to ADA criteria)  were conClinical data of all patients which included sex, age, duration of diabetes as well as a history of other diseases, were obtained by reviewing the medical records and direct patient interview.Subjects with secondary diabetes and those who on medication or have other diseases that can affect tear production were excluded.Exclusion criteria included cigarette smoking, contact lens, Lasic surgery, allergies, Sjogren's syndrome, rheumatoid arthritis, Parkinson, lupus, some medications such as antihistamines, tricyclic antidepressants, oral contraceptives, and drugs used to treat high blood pressure and diuretics. Moreover vitamin A deficiency and pregnancy were excluded.Dry eyes were suspected on the basis of a history of ocular discomfort, including soreness, gritty sensation, itchiness, redness, blurred vision that improves with blinking and excessive tearing. The condition was confirmed by ocular surface dye staining pattern with fluorescein, tear film break up time (TBUT)  and Schirmer test , according to American Academy of Ophthalmology by a specialist . DiagnosInformed consent was obtained from all subjects and the research had the approval of the institutional review board and ethics committee of the Yazd University of Medical Sciences and was carried out in accordance with the Declaration of Helsinki.Statistical analysis was performed using Statistical Package for Social Sciences . Chi square test and t- student test was used to compare discrete variables. Significance was considered to be P < 0.05. Results were given with their 95% CIs. Data were presented as means ± SD.In this study 200 diabetic patients were assessed. One patient was excluded from study because of trachoma.The mean age of subjects  was 54.16 ± 11.02 years. Of 199 subjects, 108 patients (54.3%) had dry eye syndrome which 69(58%) were female and 39(48.8%) were male. But there was not a significant association between sex and frequency of dry eye syndrome (P = 0.2) (Table 1) [See Additional file1]. Frequency of dry eye syndrome in 65–85 year old group was highest(66.7%) and in 27–41- year old group was lowest, but this correlation was not significant(P = .9) (Chart1).Of 108 patients with dry eye syndrome the mean duration of diabetes was 11.48 ± 7.4 years whereas this was 9 ± 6.5 years in subjects without dry eye syndrome. A significant association was observed between duration of diabetes and frequency of dry eye syndrome (P = .01). Dry eye syndrome was significantly higher in subjects with DR (59.3%) (p = .02) (Table 2) [See Additional file1].Of 108 patients with dry eye syndrome, 36.18% suffered from gritty sensation, 19.09% had soreness whereas none of them complains from pain and tearing. 11.5% had abnormal both TBUT and Schirmer's test and 29.64% of subjects had abnormal corneal staining. Corneal lesion, conjunctivitis, keratopathy and filamentry were not observed. The prevalence of DR in men was 76.2% (The retinopathy was mild in 10 patients (12.5%), whereas 13(16.3%) patients had moderate NPDR, 14(17.5%) had sever NPDR and 24(30%) had PDR.The prevalence of DR in women was 66.4%. The retinopathy was mild in 24 patients (20.2%), whereas 21(17.6%) patients had moderate NPDR, 8(6.7%) had sever NPDR and 26(21.8%) had PDR. There was a significant association between sex and grades of DR (P = .04) (Table3) [See Additional file1]. Prevalence of DR in 55–64 year old group was highest (84.9%) and in 24–49 year old was lowest (51.5%) (Chart 2) (Table 4) [See Additional file1].Frequency of DR was significantly higher in patients with longer duration of diabetes, it was 31.9% in patients with a history of diabetes less than 5 years, 12.48% in 5–14 years and 100% in 15 years or more (P < .0001).Of 199 subjects, 108 patients (54.3%) had dry eye syndrome. Prevalence of dry eye syndrome was significantly higher in longer duration of diabetes, but sex and age did not seem to affect dry eye syndrome.Some studies evaluated dry eye syndrome in diabetic patients. In a cohort study on 3722 subjects were aged 48 to 91 years 65 ± 10 years) and 43% male. The overall prevalence of dry eye was 14.4%. Prevalence varied from 8.4% in subjects younger than 60 years to 19.0% in those older than 80 years. Age-adjusted prevalence in men was 11.4% compared with 16.7% in women . In anot years anPrevalence of dry eye in our study is very high. It might be due to aging, dry weather in this region and high prevalence of neurological disorder in type 2 diabetic patients.Lack of control group and glycemic parameters assessment especially HbA1C could be mentioned as limitation of our study.Of 199 diabetic patients, 140 patients (70.35%) had DR. The retinopathy was mild in 34 patients (17.1%), whereas 34(17.1%) patients had moderate NPDR, 22(11.1%) had sever NPDR and 50(25.1%) had PDR. These findings are higher than previous studies ,12,22.In our study prevalence of DR significantly increased with increasing of age, but it was not true in 65–82-year old subjects, and prevalence of DR in this group decreased. Some studies showed that the prevalence of DR in late-onset diabetic patients was lower than young-onset diabetic patients ,20. A prIn our study there was significant association between sex and grades of DR. Lower grades of DR was more common in women and higher grades of DR was more common in men, such a relation was found in Rema et al Our results showed a significant association between prevalence of DR and diabetes duration, this pattern was seen in Klein et al. As the prevalence of DR varied from 28.8% in persons who had diabetes for less than five years to 77.8% in persons who had diabetes for 15 or more years .Our findings support the impression that diabetic patients have an elevated prevalence of dry eye syndrome. Diabetic retinopathy and dry eye appear to have a common association. Further studies need to be undertaken to establish an etiologic relationship. However, examination for dry eyes should be an integral part of the assessment of diabetic eye disease.The authors declare that they have no competing interests.MRM participated in the design of the study and coordination and carried out ophthalmologic examination and revising the manuscript. MR helped with study arrangement, interpretation of data and drafted the manuscript. MA-A participated in the design of the study and coordination. MRS participated in the design of the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


This paper describes the effect of including death certificate only (DCO) registrations on 5 year relative survival rates for colorectal cancer in four district health authorities (DHAs) in south-east England. A retrospective case note study was set up to examine all cases of colorectal cancer listed in the Thames Cancer Registry (TCR) as having been diagnosed in 1983 and 1988 and resident in one of four districts, A, B, C and D. A total of 673 sets of cases notes were requested from all hospitals within the four districts, including 150 sets on DCO cases. Of 465 (69%) sets of case notes retrieved, 378 (72.3%) were non-DCO cases. Of these, 14 were excluded from survival analysis because of missing dates of diagnosis or death in the notes. Eighty-seven (58.0%) sets of case notes were retrieved on DCO registrations, of which seven were excluded because no date of diagnosis was available in the notes. Retrieval rates on case note registrations varied by DHA of residence: 73.3% in DHA A, 96.6% in DHA B, 34.5% in DHA C and 79.2% in DHA D. The corresponding figures for DCO registrations were 63.5%, 69.0%, 7.4% and 76.2%. Cumulative relative 5 year survival rates by DHA of residence were calculated first for cases registered from case notes and then for all cases including those registered solely from a death certificate. The total number of cases used in the survival analysis was 444 (18% DCOs). In all four DHAs, 5 year survival decreased with the inclusion of DCO registrations: by 9.1% in district A (from 52.8 to 43.7), by 4.5% in district B (from 59.6 to 55.1), by 4.8% in district C (from 80.0 to 75.2) and by 7.6% in district D (from 31.4 to 23.8). The overall reduction in survival was 8.6%. The exclusion of death certificate only registrations from survival data is an important source of bias. Using TCR data, we compared DCO proportions for colorectal cancer with other sites. DCO proportions were shown to vary by tumour site and survival time. The DCO registration is an important quality measure of ascertainment and follow-up. OPCS should publish DCO proportions by registry area and cancer site. Registries should implement DCO monitoring as part of quality improvement programmes.


Necrotizing fasciitis (NF) is a serious infection of soft tissues. This paper presents experience with pediatric NF and suitability of conservative surgery in its management.In this retrospective study, 70 patients of NF were managed during the study period of eight years. The study was divided into two time periods- first period (June 1998 to June 2001- group 1) and second period (June 2001 to June 2006- group 2). The parameters studied were age, sex, site of involvement and treatment. The treatment included intravenous antibiotics, supportive therapy and either aggressive (group 1) or conservative surgery (group 2).Staphylococcus species. Predisposing factors included malnourishment, boils, scratch injury, intravenous cannulation and injections. Conservative surgery had better outcome in terms of hospital stay, complications and cost of treatment.Age of presentation ranged from 10 days to 11 years. Male to female ratio was 1.69:1. Back was the commonest site to be involved. Culture reports were polymicrobial in 70% with predominance of NF is a serious and disease which requires immediate and all out attention. Early diagnosis, aggressive supportive treatment and conservative surgery improve survival. Necrotizing fasciitis (NF) is a life threatening condition consisting of soft tissue infection with rapid progression and wide spread fascial necrosis. All age The mainstay of treatment is antibiotics and surgery which consists of debridement. In the standard management of NF, both for children and adults early and aggressive debridement is advocated.–5 There This was a retrospective study done from June 1998 to June 2006. All NF patients admitted were studied. The diagnosis of NF was made on clinical and microbiological basis. Patients were studied for age, sex, area of involvement, microbiology, duration of stay, and predisposing factors.The study was divided in to two time periods. In the first period (June 1998 to June 2001), early aggressive surgery was done (group 1). During this period, debridement was done immediately after the diagnosis of NF was made either in the cellulitic stage, with dusky blue patch or when gangrene of the involved skin had occurred. It involved complete removal of the necrotic tissue until the viable bleeding tissue was visible under the necrotic bed. The procedure was carried out in the operation theatre under general anesthesia. Antibiotics were used to cover gram positive , gram negative (Amikacin 7.5mg/kg IV 12 hourly) and anaerobes (Ornidazole 10 mg/kg IV 12 hourly). IV fluid was given to replace volume deficit. Analgesia was provided by intramuscular (IM) Pentazocine (0.5mg/kg). If required, IM Diazepam (0.1to 0.3 mg/kg) was given for restlessness and agitation.The second time period ranged from June 2001 to June 2006 (group 2). The management included blood investigation  before and after treatment, blood transfusion, intravenous (IV) antibiotics and debridement. The antibiotics and supportive management were same as for the group 1. In both the groups, the counts were repeated on alternate days.3) and the wound was healthy and granulating.In group 2, debridement was done three to five days after starting antibiotics intravenously and on formation of dry black skin loosely adhered to its base and separating from surrounding healthy skin . This prThe cost of treatment was evaluated on the basis of all expenses needed for surgery, medications, investigations and blood transfusions. This also included the expenses incurred by the hospital on the patient such as free drugs etc. The outcome was evaluated on the basis of hospital stay, complication and mortality.t-test, Chi square test, Fisher exact test and one way ANOVA. The values are expressed as mean plus/minus standard deviation. The P value of less than 0.05 was considered as statistically significant.All the data was entered into the Microsoft Excel sheet. The statistical analysis was done using SPSS 12.0 version for Windows. The analysis was done using paired P greater than 0.05).The total number of patients in groups 2 and 1 was 49 and 21 respectively. Both the groups had comparable age and sex distribution . In bothP greater than 0.05, In group 2 the area of involvement included back 18 (36.7%), neck and scalp nine (18.3%), thigh eight (16.3%), abdomen six (12.2%), chest five (10.2%) and arm three (6.1%). In group 1 the area of involvement included back 10 (47.62%), thigh four (19.05%), neck and scalp three (14.29%), abdomen two (9.52%) and arm two (9.52%). Both groups were comparable for the area of involvement [Staphylococcus species , S. aureus being 30 (61.2%) and S.epidermidis six (12.2%), others being Streptococcus six (12.2%), E. coli four (8.1%) and Klebsiella three (6.1%). In group1 polymicrobial culture reports were noticed in 16 (76.19%) patients, rest being unimicrobial. Both the groups were comparable regarding the type of culture [P greater than. 05, Staphylococcus species predominated in this group also .S. aureus was noticed in 13 (61.9%), S. epidermidis 4 (19.05%), Streptococcus three (14.29%) and E. coli one (4.76%).In group 2, the culture reports were polymicrobial in 32 (65.3%) and rests were unimicrobial. There was predominance of 3 with predominance of neutrophils (greater than 75%). C reactive protein (CRP) was done in 21 patients in group 2 and was uniformly raised. It was not done in rest of patients due to cost factor. In group1 CRP was not done in any of the patients because of unavailability of the facility at that time. Blood transfusion raised the hemoglobin to the level of 12 gm % to 15 gm % (mean 13.5 plus/minus 1.06 gm %) in both the groups. Total and differential leukocyte counts (TLC and DLC) normalized after five to seven days (mean 6.14 plus/minus.76 days) of treatment in group 2 and seven to 10 days (mean 8.57 plus/minus.98) in group 1 [P less than 0.001, Hemogram revealed hemoglobin in range of seven gm % to 12 gm % (mean 8.23 plus/minus 1.39 gm %) in both the groups. The serum urea and creatine levels ranged from 15 to 39 mg % (mean 21.23 plus/minus 6.17 mg %) and 0.5 to 1.1 mg % (mean 0.66 plus/minus 0.15 mg %) respectively in both the groups. Total leukocyte counts were above 13000/mmPatients were discharged after having healthy granulating wound to be healed by secondary intention or skin grafting. In group 2 36 (73.4%) patients were allowed to heal by secondary intention and the remaining 13 (26.5%) had skin grafting. In group 1 14 (66.67%) patients had healing by secondary intention and seven (33.33%) had skin grafting. The duration of hospital stay was significantly higher in group 1 .In groups 1 and 2 complications occurred in 10 (52.38%) and 11 (20.4%) patients respectively. These included septicemias, secondary wound infection, disseminated intravascular coagulation and functional disability .P greater than. 05 for mortality, In group 2, 10 patients (20.4%) expired. Three of them were premature neonates. All had poor general condition and didn't respond to the treatment. Predisposing factors included malnourishment 30 (61.2%), boils 29 (59.1%), scratch injury six (12.2%), intravenous cannulation three (6.2%), and injections two (4.1%). In group 1, five (23.81%) patients expired [On comparing this modality with the approach of aggressive early debridement, we found conservative surgery to be superior to conventional surgery Tables –3. The ret al. reported the ratio to be of 1.7:1,[NF is seen primarily in adults but ther4of 1.7:1, suggestiThe commonest area of involvement in our study was back which corresponds with other studies.10 Most o13Staphylococcus and Streptococcus.[1011Majority of the culture reports were polymicrobial which is in accordance with the various retrospective studies and reviews, predominant species being tococcus.101115 Ouccus.1011 and we mEarly diagnosis is important for early start of treatment. There are various reports of newer diagnostic modalities like USG, CT and MRI to help in early diagnosis with good results.–19Supportive therapy is needed in form of intravenous fluids, pain control and oxygWe adopted what we call as conservative surgery in managing the patient after noticing some success with delayed debridement in the literature.7 We were59et al.[et al.[According to the proponents of aggressive surgery, total excision of all necrotic tissues including muscle, fascia and skin is needed to control the progression of NF and ongoing release of bacterial toxins. In vario5et al. as we bel.[et al. recommenOur results show that conservative surgery is worth attempting as an initial choice Tables –3. ThougThe limitation of our study could be smaller group of patients in which aggressive surgery was done (group 1). This may be a reason for insignificant values for the complications discussed in the To conclude, NF in children can be a serious disease which requires immediate and all out attention. High index of suspicion, early diagnosis, aggressive supportive treatment and conservative surgery instead of aggressive surgery as and when needed may improve survival. A large prospective study comparing both the treatment modalities may throw additional light on the feasibility of conservative surgery.


A high union rate (75%-100%) with a lower incidence of avascular necrosis (8%-9.3%) has been reported with intertrochanteric osteotomy in femoral neck fractures in elderly whereas arthroplasty eliminates the incidence of nonunion and avascular necrosis We present a series of femoral neck fracture in elderly treated with modified Pauwels’ intertrochanteric osteotomy and total hip arthroplasty for their functional outcome.29 elderly patients of 60 years and above sustaining fresh subcapital femoral neck fracture underwent total hip arthroplasty  and modified Pauwels’ intertrochanteric osteotomy . Functions were evaluated using modified Harris hip score, d'Aubigne and postel criteria and SF-36 score at 6, 12, 52 and 100 weeks.The fracture union in group II was achieved in 14 (93.3%) patients at the fracture site at an average of 15 weeks and osteotomy united in all patients. Avascular necrosis of the femoral head was observed in one patient (6.7%). Average operative time was 88.9 and 65.6 minutes in group I and II, respectively . An average of 0.8 and 0.2 unit blood was transfused in patients in group I and II, respectively . Average time of full weight bearing was 6.1 weeks and 11.6 weeks in group I and group II, respectively. At 100 weeks 71.4% (n = 10) patients in group I and 80% (n = 12) patients in group II showed good to excellent results on the basis of modified Harris hip score. 71.4% (n = 10) patients in group I and 66.6% (n = 10) patients in group II showed good to excellent results on the basis of d'Aubigne criteria. Average SF-36 score was 17.2% in group I and 17.6% in group II. Revision osteotomy was performed in one patient in group II because of implant cut through. Another patient in group II underwent THR because of painful hip. One patient in group I presented with dislocation after 3 weeks of surgery.Functional results of total hip arthroplasty and intertrochanteric osteotomy are comparable and the valgus intertrochanteric osteotomy with osteosynthesis in subcapital femoral neck fractures in elderly patients of sixty years and above may be considered as an option. Various methods of internal fixation for the management of subcapital femoral neck fracture are reported with fewer postoperative complications, a shorter hospital stay and reduced cost of treatment.9810121529 consecutive patients of fresh femoral neck fracture of sixty years or above were included in this retrospective analysis. The patients of intracapsular femoral neck fracture with Garden23in situ. The blade of the double angled osteotomy blade plate was inserted in femoral head up to subchondral area along the track made with the AO chisel. Osteotomy was closed by abducting the limb and osteosynthesis of femoral neck fracture and osteotomy was achieved [th post operative day and were discharged on 12th postoperative day. Functions were evaluated using modified Harris hip score,In group II patients the fracture was reduced by traction and internal rotation under image intensifier on a conventional operation table. A longitudinal skin incision approximately 2 inches in length starting from the tip of the greater trochanter was made . First gachieved . Wound wData were analyzed with Chi-square test, Fisher's exact test and independent t test. For all tests, probability less than 0.05 were considered significant.P value = 0.76) [P value = 0.85) [P value = 0.17). All the patients in both groups were of Garden's stage IV except one patient of type III in group I . 42.9% (n = 6) patients in group I and 60% (n = 9) patients in group II were of Pauwels’ type III and remaining were of Pauwels’ type II . Average time interval between injury and operation was 13 days in group I where as it was 14.3 days in group II . In group II an average of 23.3° (20°-30°) intertrochanteric wedge was excised and an average neck shaft angle of 138.6° (128°-160°) was achieved. Post operatively femoral head was anteverted in 46.7% (n = 7) patients, retroverted in 33.3% (n = 5) patients and neutral in 20% (n = 3) patients in group II. Average operative time was 88.9 and 65.6 minutes in group I and II respectively . Blood transfusion was required in 11 patients in group I where as in group II patients it was required only in 3 patients. An average of 0.8 and 0.2 unit blood was transfused in patients in group I and II respectively . All the patients in group I were discharged only after stitch removal. In group II 14 out of 15 patients were discharged after 48-72 hours. In group I the average time period for partial weight bearing was 10.7 days and in group II it was 44.5 days post surgery . Full weight bearing was started in an average time period of 6.1 weeks and 11.6 weeks by group I and group II patients respectively . In group II union was achieved in 14 out 15 patients (93.3%) at the fracture site at an average of 15 weeks while union was achieved in all the patients at osteotomy site at an average of 14 weeks [° (10°-20°). One patient in group II developed flexion contracture of 35°. There was no incidence of mortality or infection in the series at the end of the follow up of 2 years.In group I average age of the patients was 66.5 years (60-85 years) whereas in group II it was 67.4 years (60-82 years) ( = 0.76) . In grou = 0.85) . All pat14 weeks –B. Revis14 weeks –c. In grAverage Harris hip score at 6, 12 and 100 weeks was 64.7, 75.3 and 86 respectively in group I and 61.2, 74 and 85.5 respectively in group II. At 100 weeks group I showed good to excellent results (Harris hip score >80) in 71.4% (n=10), whereas group II showed good to excellent results in 80% (n=12) patients . However after exclusion of the patients with rheumatoid arthritis and osteoarthritis from group I, average Harris hip score at 6, 12 and 100 weeks was 67.9, 78 and 88.1 respectively and good to excellent results were observed in 91% (n=10) patients  at 100 weeks. Average d'Aubigne and postel score at 6, 12 and 100 weeks was 11.2, 13.9 and 15 respectively in group I and 11, 13.8 and 14.9 respectively in group II. At 100 weeks group I showed good to excellent results (d'Aubigne and postel score >14) in 71.4% (n = 10) patients whereas group II showed good to excellent results in 66.6% (n = 10) patients . However after exclusion of the patients with rheumatoid arthritis and osteoarthritis from group I, average d'Aubigne and postel score at 6, 12 and 100 weeks was 11.5, 14.3 and 15.5 respectively and good to excellent results were observed in 91 % (n=10) patients  at 100 weeks. Average SF-36 score at 6, 12 and 100 weeks was 41.4%, 26.7% and 17.2%, respectively in group I and 44.8%, 27.2% and 17.6%, respectively in group II . However after exclusion of the patients with rheumatoid arthritis and osteoarthrosis from group I, average SF-36 score at 6, 12 and 100 weeks was 40.2%, 24.42% and 14.6%, respectively in group I .Total hip arthroplasty addresses the inherent complications of nonunion and avascular necrosis and has been the recommended method of treatment in subcapital fractures of the neck of the femur in elderly patients.27910Present analysis has been carried out on 29 patients of displaced subcapital femoral neck fracture to evaluate the functional outcome of modified Pauwels’ intertrochanteric osteotomy and total hip arthroplasty in elderly patients. Although the study is small it is a step forward in preserving patient's own viable femoral head in femoral neck fracture in elderly patients. A small number and non-randomization of patients are the limitations of the present study where as a high incidence of union and a lower rate of avascular necrosis of femoral head after follow up of 2 years is the strength of the study.The groups were comparable with respect to age, gender, side involved, severity of trauma, Singh's index, type of fracture and average time interval between injury and operation. A union rate of 93.3% (n = 14) of the fracture and 100% (n = 15) union of the osteotomy site have been achieved in an average of 15 and 14 weeks respectively in group II patients. In our previous study the authors have observed 94% and 100% union at the fracture and at the osteotomy site respectively.1929In the present study the average operation time for intertrochanteric osteotomy was significantly lower when compared with THR group . Similarly requirement of blood transfusion in group I patients was significantly higher than patients of group II . Excision of the femoral head, preparation and cementing of the acetabular and femoral components appeared technically demanding and time consuming. Recent studies have reported that excision of a 20-30 degrees intertrochanteric wedge of bone is sufficient to valgise and buttress the femoral head. Therefore, extensive preoperative planning is not required for intertrochanteric osteotomy and osteosynthesis of femoral neck fracture.34Osteotomy can be done in conventional operation theatres whereas THR requires specialized operation theatre to reduce chances of infection. In the underdeveloped and developing countries only a fewer operation theatres suitable for THR are available. Internal fixation resulted in fewer postoperative complications, a shorter hospital stay and a reduced cost of treatment has been reported in other series also.7Pauwels’ intertrochanteric osteotomy has been used to modify the mechanical environment about the proximal femur, thereby placing the head of femur at right angle to the resultant of body weight forces.37Retroversion of the femoral head caused limitation of extreme flexion in group II patients in the present series; an observation also reported in our previous studies.293810121427Squatting on toes and cross leg position is an essential component of day to day sociocultural activities of the people of third world countries. The external rotation deformity between 10°-20° in group II patients helped them squatting and sitting cross leg. Inability to squat on toes and cross leg position is another disadvantage of THR.Collapse at the fracture site is a serious complication observed in one of our patients in group II. The tip of the blade penetrated the joint resulting in painful hip which necessitated THR. Conversion of failed osteosynthesis and intertrochanteric osteotomy into a THR does not compromise subsequent hip arthroplasty.46Intertrochanteric osteotomy is a simple and biological procedure. 93.3% (n = 14) union can be achieved in femoral neck fracture in elderly patients and if the procedure fails it can be revised. Since the present non randomized series is small, a larger randomized series is suggested. Delayed rehabilitation is a disadvantage of intertrochanteric osteotomy and full weight bearing is not permitted until union of the fracture and osteotomy. External rotation deformity though preventable helps Indian patients sitting in squatting position in external rotation. Functional results of total hip replacement and intertrochanteric osteotomy are comparable and justify the usefulness of valgus intertrochanteric osteotomy with osteosynthesis in femoral neck fractures in elderly patients of sixty years and above.


Genomic instability is a driving force for tumorigenesis. p53 and telomerase play central roles in maintaining genomic integrity. The purpose of this study was to assess the associations among p53 protein overexpression, telomerase activity and genetic instability in lung cancer. We found that telomerase activity was detectable in 80% of 100 lung tumours, but only 7.7% of 91 paired adjacent normal tissues. p53 protein was overexpressed in 63% of the tumours but only 2% of the normal tissues. p53 was overexpressed in 56 of the 80 (70%) tumour tissues with telomerase activity but only seven of the 20 (35%) without telomerase activity. p53 protein overexpression carried a 6.7-fold  increased risk for positive telomerase activity after adjustment by age, sex, ethnicity, smoking status and family history of lung cancer. The mean in vitro bleomycin-induced breaks per cell (a marker of cancer susceptibility) was significantly higher (0.92) for patients who overexpressed p53 in lung tumour tissue than that for patients with no detectable p53 expression in lung tumour tissue (0.65). Our data suggest that p53 protein overexpression may be common in individuals genetically susceptible to carcinogen exposure. p53 status may be related to telomerase expression. © 1999 Cancer Research Campaign


Time trends in therapeutic approaches and in the prognosis of colon cancer for patients aged 75 years and above have been investigated in comparison with corresponding trends for younger patients using a population-based series of 2089 colon cancer patients diagnosed between 1976 and 1990 in the CÃ´te-d'Or area , Burgundy, France. Significant progress has been achieved in the management of patients with colon cancer in both age groups, but trends have been more noticeable in patients aged 75 years and above. In the elderly, the proportion of cancers limited to the digestive tract wall showed a 3-year average increase of 2.8% (P = 0.02) and the frequency of curative surgery an average increase of 8.6% (P < 0.001), so that it was performed in 80% of cases in the last 3-year period. Operative mortality decreased by 2.5% between 3-year periods (P < 0.004). Crude 5-year survival rates in elderly patients increased from 15% in the 1976-78 period to 29% in the 1985-87 period (P < 0.001), the corresponding figures being 36% and 44% (P > 0.10) in younger patients.


Coxiella burnetii, is endemic in northern Spain where it has been reported as responsible for large series of human pneumonia cases and domestic ruminants' reproductive disorders. To investigate pathogen exposure among domestic ruminants in semi-extensive grazing systems in northern Spain, a serosurvey was carried out in 1,379 sheep (42 flocks), 626 beef cattle (46 herds) and 115 goats (11 herds). Serum antibodies were analysed by ELISA and positive samples were retested by Complement Fixation test (CFT) to detect recent infections.Q fever, a worldwide zoonotic disease caused by C. burnetii antibody prevalence was slightly higher in sheep (11.8 ± 2.0%) than in goats (8.7 ± 5.9%) and beef cattle (6.7 ± 2.0%). Herd prevalence was 74% for ovine, 45% for goat and 43% for bovine. Twenty-one percent of sheep flocks, 27% of goat and 14% of cattle herds had a C. burnetii seroprevalence ≥ 20%. Only 15 out of 214 ELISA-positive animals reacted positive by CFT. Age-associated seroprevalence differed between ruminant species with a general increasing pattern with age. No evidence of correlation between abortion history and seroprevalence rates was observed despite the known abortifacient nature of C. burnetii in domestic ruminants.ELISA anti-C. burnetii in the region but also that cattle and goats should not be neglected as part of the domestic cycle of C. burnetii. This work reports basic epidemiologic patterns of C. burnetii in semi-extensive grazed domestic ruminants which, together with the relevant role of C. burnetii as a zoonotic and abortifacient agent, makes these results to concern both Public and Animal Health Authorities.Results reported herein showed that sheep had the highest contact rate with  Coxiella burnetii, a ubiquitous Gram-negative bacterium that is able to infect humans and a wide range of animals, both aquatic and terrestrial 1/2 [ELISA anti-culation . A herd p)/n]1/2 .C. burnetii seroprevalence of 11.8 ± 2.0% (RGC: 7.1 ± 1.4%) in sheep, 8.7 ± 5.9% (RGC: 3.9 ± 3.5%) in goats and 6.7 ± 2.0% (RGC: 1.8 ± 1.0%) in beef cattle. Statistically significant differences were found between cattle and sheep seroprevalences . The percentage of seropositive herds was 74% (34/46) for sheep, 43% (18/42) for cattle and 45% (5/11) for goats. Within-herd seroprevalence values ranged 0-80% for sheep, 0-53% for cattle and 0-30% for goats, with 21%, 14% and 27% of the herds, respectively, showing a C. burnetii seroprevalence ≥ 20%.ELISA test showed an average Eight out of 162 (4.9 ± 3.3%), 6 out of 42 (14.3 ± 10.6%) and 1 out of 10 (10.0 ± 18.6%) ELISA-positive sheep, cattle and goats, respectively, also reacted positive in the CFT giving titres ≥ 1/10. CFT positive ewes belonged to 5 herds  and antibody titres did not exceed 1/20. In cattle, CFT positive animals belonged to 3 herds  and antibody titres did not exceed 1/40. Finally, only one goat reacting positive in ELISA also reacted in the CFT showing a titre of 1/10.C. burnetii seroprevalence tended to increase from yearlings to adults in sheep and goats, seroprevalence values remained similar for heifer and adult cattle. Nonetheless, no statistically significant differences between age class seroprevalence values were found. In addition, anti-C. burnetii antibody prevalence did not differ statistically in relation to herd abortion history, neither in sheep (9.1 ± 3.9% for flocks reporting abortion and 9.0 ± 2.0% for non-reporting flocks) nor in cattle . Seven of the 23 interviewed sheep flock owners reported recent problems of abortion. Five of these flocks were positive for ELISA anti-C. burnetii antibodies, with seroprevalences ranging between 3.3% and 36.7%. Interestingly, CFT titres ≥ 1/10 were detected in only one of those flocks. Meanwhile, 5 of 18 cattle herds reported abortion problems and showed seroprevalences between 0% and 20%, but none of the ELISA positive animals from those herds reporting abortion had significant CFT titres. Conversely, 6 of 13 cattle herds reporting no reproductive problems showed seroprevalences between 6.6% and 53.3% by ELISA, and in 2 of these herds several animals showed titres ≥ 1/10 against Coxiella by CFT. Recent abortion history could only be obtained from a small number of goat herds (n = 4) and consequently we did not considered them in the analysis.ELISA seroprevalence-age associated patterns differed between ruminant species Table . While CC. burnetii infection. Moreover, C. burnetti was found to be widespread in sheep flocks [C. burnetii among livestock in the Basque Country, we studied the seroprevalence in beef cattle, sheep and goats, which are reared in semi-extensive conditions, while intensively managed species (dairy cattle) will be the subject of a future study.Q fever is considered a strongly endemic disease in humans in the Basque Country ,33. Contp flocks  and is kp flocks  that cauC. burnetii antibodies were the reasons for using this technique for epidemiological purposes in the current study. Although ELISA test can fail to detect C. burnetii contact at an individual level [C. burnetii infected animals. Nonetheless, the high variability of C. burnetii excretion by animals throughout the year limits the reliability of molecular methods for epidemiological purposes, especially if sampling takes place outside of the reproductive season.Comparison of herein reported ELISA results with other epidemiological surveys has to be carefully considered due to the different serological techniques employed. While recent studies tend to use the indirect fluorescence assay (IFA) or ELISA, those carried out some decades ago used mainly CFT. Whereas IFA and ELISA tests on ruminant sera showed similar results, low agreement was observed between ELISA and CFT ,36, whicC. burnetii zoonosis associated to sheep in all the Mediterranean countries. Nevertheless, seroprevalence of cattle and goats in some of these countries suggest that these species would also represent a potential risk. In fact, cattle seropositivity ranged between 5.8% and 25% [C. burnetii [The seroprevalence found in sheep was comparable to that reported in other Spanish regions where seroprevalence ranged between 1.7% and 18.8%  or in so and 25% ,37, and  and 25% ,24,38. Iburnetii .C. burnetii in livestock suggest that local productive system and management factors might influence the life cycle of C. burnetii. Moreover, wildlife could play a relevant role as reservoir for livestock [C. burnetii by infected animals is higher because of parturition [The lower seroprevalence observed in the present study in cattle and goats could be explained by the semi-extensive management conditions in which animals are moving during part of the year in large land surfaces thus reducing the contact between animals. Therefore, the different prevalences of ivestock , especiaturition . InteresC. burnetii serological patterns have been seldom reported in the scientific literature in regard to domestic ruminants [Age-related uminants ,34. PathC. burnetii in the surveyed herds together with the random selection of sampled animals could explain the lack of association found between herd seroprevalence and abortion reports. Different results have been reported in this regard, with significant associations between seroprevalence and abortion reported for cattle and sheep in several studies [C. burnetii in cattle did not result in abortion, suggesting that infection sometimes can pass unnoticed [C. burnetii. Although several farmers did not report abortion or reproductive problems, high seroprevalences can be associated with the presence of C. burnetii in the herd. Similarly, Astobiza et al. [C. burnetii shedders at lambing (55-79%) in a sheep flock with a low rate of abortion (3.4%). These observations indicate that there are several epidemiological and clinical aspects of C. burnetii infection that need to be elucidated and require further investigation.Long-time contact with  studies ,37, whernnoticed . In the a et al.  found a C. burnetii in the region, but also that cattle and goats should not be neglected as part of the domestic cycle of C. burnetii. Based on our observations, we can conclude that measures are to be implemented for the control of C. burnetii and Q fever in the study region along the line of those currently in operation in other European countries. Moreover, further epidemiological research on herd, local and regional factors influencing C. burnetii life cycle is needed in order to establish more efficient control measures that prevent spread of the infection and its associated effects on livestock and humans. At present, a control programme based on vaccination using a Phase I vaccine is in progress and its efficacy will be assessed in the near future.The results reported herein showed that sheep had the highest contact rate with FR was responsible for data collection and statistical analysis, and wrote the manuscript; JFB, JA and RA helped in the samplings and performed the serological tests; AH assisted with the interpretation and discussion of results and correcting the manuscript; RAJ advised on statistical analysis and critically revised the manuscript. ALG is head of the project and had primary responsibility for the investigations reported here. All authors revised the manuscript and approved it in its final version.


Previous studies have reported increased risk of myocardial infarction (MI) after increases in ambient particulate matter (PM) air pollution concentrations in the hours and days before MI onset.2.5) may be associated with increased risk of MI and that chronic obstructive pulmonary disease (COPD) and diabetes may increase susceptibility to PM2.5. We also explored whether both transmural and nontransmural infarctions were acutely associated with ambient PM2.5 concentrations.We hypothesized that acute increases in fine PM with aerodynamic diameter ≤ 2.5 μm , as well as ambient measurements of PM2.5, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone.We studied all hospital admissions from 2004 through 2006 for first acute MI of adult residents of New Jersey who lived within 10 km of a PM2.5 concentration (10.8 μg/m3) in the 24 hr before arriving at the emergency department for MI was not associated with an increased risk of MI overall but was associated with an increased risk of a transmural infarction. We found no association between the same increase in PM2.5 and risk of a nontransmural infarction. Further, subjects with COPD appeared to be particularly susceptible, but those with diabetes were not.Using a time-stratified case-crossover design and conditional logistic regression showed that each interquartile-range increase in PM2.5 concentrations should be stratified by infarction type.This PM–transmural infarction association is consistent with earlier studies of PM and MI. The lack of association with nontransmural infarction suggests that future studies that investigate the triggering of MI by ambient PM Most previous studies , but not2.5) triggers all infarctions, whether PM–MI associations differ in magnitude, or whether these associations are restricted to PM–transmural or PM–nontransmural infarctions alone. Such investigations may provide insight into the mechanisms by which PM may trigger cardiovascular events.Numerous researchers have reported that the percentage of infarctions that are nontransmural has been increasing . More re2.5 studies that were conducted in other U.S. and European cities. We hypothesized that increases in mean PM2.5 concentration on the same day and a few days before ED arrival for MI may be associated with increased risk of MI and that these effect estimates would be greater for persons with diabetes and those with COPD than for individuals without these conditions. Further, we explored whether there were differences in risks associated with increases in ambient PM2.5 concentration between transmural and nontransmural infarctions.Using the same data as International Classification of Diseases, version 9 (ICD-9), codes 410.01, 410.11, 410.21, 410.31, 410.41, 410.51, 410.61, 410.71, 410.81, and 410.91] for patients who were admitted between 1 January 2004 and 31 December 2006, were ≥ 18 years of age, were residents of New Jersey at the time of their MI, and who were without a previous diagnosis of MI (ICD-9 code 412). Because the “1” in the fifth digit of the ICD-9 code  indicates a first MI for the subject, we also used this designation to exclude those persons who had had a previous MI. Those who were not admitted into the hospital  were not included in this data set. We classified patients with an MI coded as 410.7  as having a nontransmural infarction, and those with codes 410.0 , 410.1 , 410.2 , 410.3 , 410.4 , 410.5 , and 410.6  as having transmural infarctions.Using the Myocardial Infarction Data Acquisition System (MIDAS), a statewide surveillance system in New Jersey that combines hospital discharge data and death certificate registration data , 2001, wFrom these extracted data, we also retained the following variables: date and hour of ED admission; ZIP code of residence; age; sex; race; variables indicating the presence or absence of other comorbid conditions (based on ICD-9 codes)—congestive heart failure (ICD-9 code 428.0), arrhythmia , hypertension (ICD-9 codes 401–405), diabetes (ICD-9 code 250), COPD (ICD-9 codes 490–496), and history of ischemic heart disease (ICD-9 codes 410–414); and variables indicating in-hospital and postinfarction procedures (based on ICD-9 code)—angioplasty, CABG, and catheterization.This study and the original MIDAS study were approved by the University of Medicine and Dentistry of New Jersey–New Brunswick Institutional Review Board. MIDAS was also approved by the New Jersey Department of Health and Senior Services Institutional Review Board.2.5 (7 monitoring stations), nitrogen dioxide , sulfur dioxide , carbon monoxide , and ozone  for the study period 1 January 2004 to 31 December 2006. For each patient, we calculated the distance between each PM2.5 monitor (in operation at the time of the MI) and the patient’s residence and assigned PM2.5 measurements from the closest monitor to their residence. Those patients who lived > 10 km from a PM2.5 monitoring station were excluded from PM2.5 analyses. We calculated mean PM2.5 concentrations for each successive 24-hr period before ED arrival for the MI . If > 6 hr (> 25%) of a 24-hr period of PM2.5 concentrations were missing, we set the mean for this 24-hr period of PM2.5 concentration to missing. We used these mean concentrations in all analyses. We repeated this monitor matching and mean concentration calculation process for each of the other pollutants.Using ambient pollutant measurements from the New Jersey Department of Environmental Protection and from U.S. Environmental Protection Agency (EPA) Web sites , we usedHourly temperature and dew point measurements were made at the Newark, Caldwell, Somerset, and Trenton, New Jersey, airports during the study period. We used the airport monitor closest to each patient’s residence to provide the weather observations for that patient during the study period. After calculating 24-hr mean temperature and dew point, in the same manner as for the pollutant concentrations, we calculated 24-hr mean apparent temperature  as a meaWe used a time-stratified case-crossover design  that has2.5 concentration in the 24 hr before ED arrival. Using Akaike’s information criterion to select the optimal lag time and number of degrees of freedom for apparent temperature, we also included a natural spline (3 degrees of freedom) of the mean apparent temperature in the 48 hr before ED arrival in the model. We then reran this same model, replacing the 24-hr mean PM2.5 concentration (for both case and control periods) with one of six lagged mean PM2.5 concentrations  to estimate the risk of MI associated with each lagged PM2.5 concentration. From each model, we present the odds ratio (OR) and its 95% confidence interval (CI) scaled to the interquartile range (IQR) of PM2.5 observed during the study period. A p-value < 0.05 was used to indicate statistical significance.Using a conditional logistic regression model stratified on each MI (one case and three or four control periods), we regressed case–control status  against the mean PM2.5 concentration in the 24 hr before ED arrival was different for patients with transmural versus nontransmural infarctions. We reran the same model described above for patients with transmural infarctions only, and then for patients with nontransmural infarctions only. To examine potential effect modification by other factors, including COPD, diabetes, age , sex, race , and season , we used an interaction term  in the main model.Next, we examined whether the risk of MI associated with an IQR increase in mean PM2.5 relative risk estimates after adjusting for gaseous pollutant concentrations, we created two-pollutant models  using mean pollutant concentrations from the 24 hr before ED arrival. We also evaluated whether any association between ED arrival for MI and the mean PM2.5 concentration in the previous 24 hr was independent of concentrations from previous 24-hr periods. We reran the same conditional logistic regression model described above, including all seven lagged PM2.5 concentrations .To assess the stability of our PMAll data sets included in the analyses were constructed using SAS software , and all analyses were conducted using R . The authors had full access to the data and take responsibility for its integrity.2.5 monitoring site and had PM2.5 data available for analysis . Study patients were predominantly older (59% > 65 years of age), white (69%), and male (56%). Sixty-two percent had hypertension, 61% had a history of ischemic heart disease, and 30% had diabetes , Camden Lab (26%), and New Brunswick (18%) monitors. The distribution of mean daily PM2.5 concentrations at each of these seven monitors is shown in 2.5 concentrations had a median of 11.7 μg/m3; 5th and 95th percentiles of 3.6 and 31.5 μg/m3, respectively; and 25th and 75th percentiles of 7.4 and 18.3 μg/m3, respectively (IQR = 10.8 μg/m3). We scaled all our effect estimates presented below by this IQR. Of the seven monitors that were continuously measuring PM2.5 concentration in the previous 24 hr, and lagged 24-hr periods , adjusting for apparent temperature during that same lag period. Each 10.8-μg/m3 increase in the mean PM2.5 concentration in the 24 hr before ED arrival was not associated with an increased risk of MI . When examining lagged PM2.5 concentrations, the relative risk estimates were mostly > 1.0, but none was statistically significant. In contrast, when we restricted our analysis to nontransmural infarctions, we found no increased risks associated with any lagged PM2.5 concentrations . The PM2.5 relative risk estimate in this two-pollutant model was not substantially different from the single-pollutant model on the same n = 1,262 patients . All the PM2.5 concentration relative risk estimates for the other lag periods were smaller than the 24-hr moving-average relative risk estimate, and none was statistically significant (data not shown).We then included mean PMpatients . This want model . Next, w2.5 concentrations in the previous week. However, when we restricted the analysis to patients with transmural infarctions, we found a significant 10% increase in the risk of a transmural infarction associated with the mean PM2.5 concentration in the 24 hr before ED arrival. This association persisted with adjustment for gaseous pollutant concentrations in the prior 24 hr and with adjustment for PM2.5 concentrations during each of the previous six 24-hr periods. Further, patients with COPD, but not diabetes, were particularly susceptible to acute increases in ambient PM2.5 concentrations. We found no association with this same PM2.5 concentration and nontransmural infarctions.Using a large multiyear (2004–2006) statewide data set of hospital admissions for first MI, we found no association between admission for MI overall and PM10, PM2.5) are not uniform. Previous studies reported PM associations with all MIs, not just transmural infarctions . Therefore, we did not examine associations with ambient PM2.5 concentrations < 24 hr before ED arrival, but instead focused on associations between infarctions and the ambient air pollution concentration in the 24 hr before ED arrival for that MI. Our finding of an association between increased 24-hr mean PM2.5 concentrations and transmural infarction needs to be replicated in a study that better estimates MI symptom onset time. This study would also allow a more proper investigation of the risk of a transmural infarction associated with PM2.5 concentrations < 24 hr before MI symptom onset than is possible in our analysis.Third, linking MIs to hourly and daily air pollution fluctuations requires minimizing misclassification of the estimate of MI onset time, so as to minimize bias. Although four previous studies  have use2.5 concentration in the 24 hr before ED arrival may not have been before the onset of MI symptoms, this again was a source of nondifferential exposure misclassification that may have resulted underestimates of relative risk. As reported by Fourth, because all of the 24 hr used to calculate the mean PM2.5 concentrations to all patients who lived < 10 km from a PM2.5 monitor, regardless of how close they lived to the monitor or how much time they spent at locations other than their residence. Because this error is not likely differential with respect to when a patient had the MI, it likely resulted in nondifferential exposure misclassification and underestimates of relative risk. In the two pollutant analyses adjusting for gaseous pollutant concentrations, gaseous pollutants may have greater degrees of spatial variability than does PM2.5 within this 10-km radius, resulting in residual confounding.Last, we assigned PM3 increase in mean PM2.5 concentration in the 24 hr before ED arrival. Further, patients with COPD, but not those with diabetes, appeared particularly susceptible to effects of ambient particles. If our findings are confirmed, future investigations of PM and MI triggering should stratify by type of MI, with particular emphasis on transmural infarctions. Future work should also investigate mechanistic explanations for these findings.We found increased risk of transmural infarctions, but not nontransmural infarctions, associated with each 10.8 μg/m


Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures.Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student's t test and Fisher's exact test.vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant.The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results. Various methods were designed to treat thoracolumbar burst fractures. Nonoperative treatment including bed rest and mobilization with brace5651015A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture and Kümmell's disease.1720The operation time and blood loss for posterior fixation and vertebral body reconstruction with the augmenter was similar to posterior fixation alone and the additional augmentation helped maintain the reduction of the vertebral body, leading to clinical success in the short term.et al.et al.et al.We retrospectively reviewed 162 patients with thoracolumbar burst fractures who were treated with posterior short-segment fixation from January 1998 to June 2003. Patients included in the study had neurological function limited to Frankel Grades C, D or E.The clinical results were based on the latest followup as of May 31, 2007. The followup rate was 81.5%. Eight patients died of unrelated medical illnesses and 22 patients were lost to followup. These 30 patients were excluded from this retrospective study; 132 patients  were included . The meaThe preoperative evaluation protocol included anteroposterior (AP) and neutral lateral thoracolumbar radiographs, computed tomography (CT) scans and magnetic resonance imaging (MRI) scans to evaluate fracture sites and cord compression status. The pedicle size was measured on the CT or plain AP and lateral radiographs.®, Wright Medical Technology, Arlington, TN) if the autograft from the posterior iliac bone was insufficient. Then the augmenter was inserted into the vertebral body through the pedicle tunnel and finally, bone graft was used to fill the pedicle tunnel space [All the patients initially received manual reduction and short-segment fixation. Manual reduction was done as Li's previous reports.171317el space . PatientSerial radiographs  were obtained regularly at immediate and 3 months after surgery. Flexion and extension radiographs were obtained after one year and at the final visit.et al.,et al.et al.The sagittal plane kyphosis angle was measured as described by Kuklo P < 0.05.Student's t test was used for statistical analysis of kyphotic deformity, kyphosis correction and anterior vertebral height. Fisher's exact test was used to analyze the instrument failure rate and pain scale data. The data are presented as mean ± standard deviation. The level of statistical significance was set at The operation time and blood loss were similar in both the groups. The mean operation time for the augmented group was 63.3 ± 13.2 min, vs. 63.1 ± 17.2 min for the control group. Blood loss was 227 ± 71 cc and 242 ± 89 cc for the augmented and control groups, respectively. The duration of hospitalization was also similar for both the groups . Complications included eight superficial infections (five patients in the augmented group and three patients in the control group), one deep vein thrombosis in the augmented group and one deep infection in the control group. In the early stage, one patient in the augmented group had an intraoperative pedicular medial cortex rupture during TpBA insertion, which caused root irritation and neuralgia, necessitating revision surgery to remove the augmenter three weeks later. No other pedicle injury during TpBA insertion happened thereafter.P < 0.001) in the augmented group than in the control group [Anterior vertebral height restoration and kyphotic correction was achieved and well maintained in the augmented group. The preoperative anterior vertebral height of the fractured vertebral body and kyphotic deformity were similar in both groups. The immediate postoperative anterior vertebral height and kyphosis were not different between the augmented and control groups. At the last followup, however, anterior vertebral height was greater (ol group . The redol group 4.P < 0.001) implant failure (0% (n=0) vs. 23.8% (n=10) for the control group) and better clinical results. The control group had 10 implant failures and increase in kyphosis. No dislodgement of the transpedicle body augmenter occurred. Based on the pain scale of Denis et al.,P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group (90.0% (n=81) vs. 66.7% (n=28)). The augmented group had fewer patients (P < 0.001) with severe and constant pain (Grades P4 and P5) than the control group (0% (n=0) versus 16.7% (n=7)) [The TpBA-augmented group had less (% (n=7)) . All patA transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture and Kümmell's disease.176510As discussed before,23et al.et al.et al.et al.et al.et al.,et al.,et al.et al.Posterior short-segment fixation with the TpBA is relatively effective in preventing loss of reduction and avoiding implant failure. Loss in reduction of kyphosis after short-segment fixation (e.g. 90% by Carl The longterm results showed that adjacent disc injury in thoracolumbar burst becomes a minor problem after TpBA has been used. Discs adjacent to the burst fracture are extensively damaged,32Once the technique is mastered, the TpBA can be used with its best benefit and without complications. To ensure the security and adequate restoration of the vertebral body, the optimal size of TpBA should be chosen. The pedicle size is different among individuals and spine levels.34Short-segment fixation with reinforcement of a transpedicle body augmenter is an effective and safe method to treat burst fractures. With an average followup of more than five years we showed that TpBA could ensure restoration of vertebral bodies, prevent implant failure and lead to clinical success.


Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. We explore whether schizophrenia and affective disorder have common susceptibility gene on 6q in Han Chinese population.In the present study, we genotyped 45 family trios from Han Chinese population with mixed family history of schizophrenia and affective disorder. Twelve short tandem repeat (STRs) markers were selected, which covered 102.19 cM on chromosome 6q with average spacing 9.29 cM and heterozygosity 0.78. The transmission disequilibrium test (TDT) was performed to search for susceptibility loci to schizophrenia and affective disorder.The results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. When families were grouped into schizophrenia and affective disorder group, D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05).These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population. The distinction between schizophrenia and affective disorder was historically based on distinct phenomenologies and long-term courses. A differential nosology and etiology was postulated, however never convincingly proven . OpinionSeveral linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. The first report of linkage findings on 6q13-26 in schizophrenia came from  which haA mixed family was defined as one in which members suffer from both schizophrenia and affective disorder separately, namely at least one patient with schizophrenia and another patient with affective disorder among three-generation relatives. We recruited 45 family trios, composed of the probands and their biological parents, with mixed family history of schizophrenia and affective disorder. Here the probands were outpatients or inpatients from Shanghai Mental Health Center. Clinical diagnosis was made according to ICD-10; an independent clinician using the same criteria reviewed all diagnoses. Blood samples were obtained from the family trios. The investigation was carried out in accordance with the latest version of the Declaration of Helsinki, that the study design was reviewed by an appropriate ethical committee and that informed consent of the participants was obtained after the nature of the procedures had been fully explained. The probands included 21 male patients and 24 female ones, 26 diagnosed with schizophrenia and 19 with affective disorder , mean age of patients were 28.7 ± 8.9 years, mean age of onset were 22.7 ± 8.0 years, mean duration were 5.9 ± 6.4 years; and the mean age of their parents were 58.5 ± 10.4 years.Genomic DNA was extracted from peripheral blood leukocytes of each subject. The short tandem repeat (STR) markers used in this study were modified from the ABI PRISM Linkage Mapping Set Version 2.5. These included 12 STRs  on chromosome 6q, which spanned 102.19 cM with a mean interval of 9.29 cM, heterozygosity of each STR above 0.50 and average heterozygosity 0.78 , where preferential allelic transmission from heterozygous parents to affected offspring is tested by applying (b-c)2/(b+c) statistics (Mc Nemar's equation) and χ2 test.Hardy-Weinberg equilibrium and statistical differences in genotype and allele frequencies between probands and parents were evaluated using the χP > 0.05). Taking all family trios as study subjects, we found five STRs D6S257 at 79.92 cM, D6S460 at 89.83 cM, D6S1021 at 112.20 cM, D6S292 at 136.97 cM and D6S1581 at 164.78 cM were associated with susceptibility to psychotic disorders (see table P > 0.05).The genotype distributions of total markers in the patient group and parent group did not deviate significantly from Hardy-Weinberg equilibrium in the patient or parent group  declare that they have no competing interests.Dr. Zuowei Wang and Prof. Yiru Fang participated in the design of the study and drafting the manuscript. Dr. Zuowei and Dr. Shunying Yu carried out the molecular genetic studies, participated in the sequence alignment and performed the statistical analysis. Dr. ChengMei Yuan Dr. Wu Hong, Dr. Zhenghui Yi, Prof. Sanduo Jiang and Prof. Zucheng Wang participated in sample collection. Prof. John R. Kelsoe helped to review the manuscript. All authors read and approved the final manuscript.


Pain is common in head and neck cancer (HNC) patients and may be attributed to the malignancy and/or cancer treatment. Pain mechanisms and patient report of pain in HNC are expected to include both nociceptive and neuropathic components. The purpose of this study was to assess the trajectory of orofacial and other pain during and following treatment, using patient reports of neuropathic pain and nociceptive pain and pain impact.124 consecutive HNC patients receiving radiation therapy (RT)  participated in a patient-reported outcome (PRO) assessment. Patients completed the McGill Pain Questionnaire three times during therapy and 3 months following study entry.The majority of patients related their pain to the tumor and/or cancer treatment. Whereas 59% reported their pain to be less severe than they expected, 29% were not satisfied with their level of pain despite pain management during cancer therapy. Worst pain was 3.0 ± 1.3 on a 0- to 5-point verbal descriptor scale. Pain intensity was present at entry, highest at 2-week follow-up, declining towards the end of treatment and persisting at 3-month follow-up. The most common neuropathic pain descriptors chosen were aching (20%) and burning (27%); nociceptive words chosen were dull (22%), sore (32%), tender (35%), and throbbing (23%), and affective/evaluative descriptors were tiring (25%) and annoying (41%). 57% of patients reported continuous pain, and combined continuous and intermittent pain was reported by 79% of patients.This study provides evidence that patients with HNC experience nociceptive and neuropathic pain during RT despite ongoing pain management. The affective and evaluative descriptors chosen for head and neck pain indicate considerable impact on quality of life even with low to moderate levels of pain intensity. These findings suggest that clinicians should consider contemporary management for both nociceptive and neuropathic pain in head and neck cancer patients. Pain is common for the 35,310 people who are diagnosed with head and neck cancer (HNC) in the United States annually . HNC paiNeuropathic pain is defined by The International Association for the Study of Pain (IASP) as pain initiated or caused by a primary lesion or dysfunction in the nervous system resulting in debilitating pain . Damage One of the most feared consequences of cancer is the possibility of severe and uncontrolled pain in patients with advanced cancer . In patiCancer pain causes increased morbidity, reduced performance status, increased anxiety and depression, and diminished quality of life (QOL) ,26-28. HPain may be the first symptom in 20% to 50% of all cancer patients  due to tIn HNC patients, neuropathic pain has not been well characterized in terms of sensory report  or sensory quantification . Grond et al.  reportedWe conducted a 3-month repeated-measures study to describe the trajectory of pain and pain descriptors in consecutive patients with HNC. The study was approved by the Institutional Review Board at the University of Washington for initial data collection and at the University of Illinois at Chicago for ongoing data analysis.Eligible subjects: (a) had a diagnosis of HNC; (b) spoke and read English; and (c) had pain related to the cancer or to cancer therapy during the week prior to enrolling. Patients were excluded if they: (a) had surgery within one month; (b) were physically unable to complete study procedures; or (c) were mentally unable to complete study questionnaires because of brain metastases or developmental problems, as measured by a Mini-Mental State Exam (MMSE)   and exported it to SPSS  for data analysis. We present descriptive statistics for the pain location, intensity, quality, and pattern, as well as the number of nociceptive and neuropathic descriptors reported at each measurement time point. Pain quality findings are reported for the first pain site reported that was located in the head and neck region. We plotted scores and calculated repeated-measures ANOVAs over time for pain scores reported during the 3-month study.Patient characteristics are shown in Table Prior to study entry, the majority of patients reported pain for 0–6 months (77%), 7–12 months (5.6%), 13–23 months 4%), or more than 2 years (12.9%). At baseline, patients associated their pain with their cancer (21%), surgery (53.2%), or both tumor and surgery (20.5%). On average, patients reported 2.1 ± 2.2 pain sites. Pain measures at baseline are shown in Table %, or morThe pain intensity scores presented in Table F = 48.5, p < 0.001); the number of the nociceptive words chosen  = 51.2, p < 0.001)  = 11.9, p < 0.001); PRI-A  = 1.5, p < 0.21); PRI-E  = 3.5, p < 0.02); PRI-M  = 2.6, p < 0.05); PRI-T  = 9.2, p < 0.001)  = 8.7, p < 0.001).Pain scores decreased from admission to last follow-up. ANOVA showed significant decreases in the pain measures over the 4 time points: the number of the neuropathic words chosen . At time 3, worst pain was 2.89 ± 1.23, and at time 4 worst pain was 2.54 ± 1.40, current pain 1.02 ± 1.07 and least pain 0.60 ± 0.81 , 21% adjuvant analgesics, 8.1% step 2 opioids (for mild to moderate pain intensity), 20.2% step 3 opioids (for moderate to severe pain intensity). The other patients were taking combinations of analgesics and adjuvant drugs: 8.9% adjuvant and step 1 analgesics; 3.2% adjuvant and step 2 opioids; 4% adjuvant and step 3 opioids; 6.5% step 1 and step 2 opioids; 1.6% step 2 and step 3 opioids; 1.6% adjuvant, step 1, and step 2 opioids; 0.8% adjuvant, step 1 and step 3 opioids; and 11% were missing analgesic drug data.We estimated adequacy of analgesic prescription by calculating a pain management index (PMI) as suggested by Cleeland ,56. We sHNC patients were enrolled in the study during cancer treatment when pain was reported. Patients attributed their pain to the cancer, prior surgical treatment or the ongoing radiation therapy for HNC. Pain was discomforting on average at entry (worst pain intensity 3.0 ± 1.3), and it was less than anticipated in more than half of the patients, as expected in about one-fifth and worse than expected by some. In our survey, pain was reported first in the head and neck or oral cavity by 79% (n = 98) of the participants.In a previous study, pain was reported by patients with oral squamous cell carcinoma at presentation in 39% of 138 cases and correlated with tumor stage . Pain atNeuropathies are commonly reported in patients with malignancy (1.7%–5.5%) and may be due to direct effects of the tumor, paraneoplastic syndromes and/or treatment-related toxicity -64. NeurThe most common acute oral side effect of chemotherapy and radiotherapy is oral mucositis . Oral muSurgical procedures commonly result in acute nociceptive orofacial pain and establish conditions that may lead to painful post-surgical neuropathy. In addition to tissue injury at tumor resection, morbidity is increased by concomitant procedures such as radical neck dissection . In thisThe affective and evaluative descriptors chosen for head and neck pain indicate considerable impact on quality of life, even with low to moderate levels of pain intensity. Effective management requires accurate diagnosis of the multifaceted etiology of orofacial pain in cancer patients ,86. PainNociceptive pain is managed with treatment of the cause and topical anesthetics and analgesics, with reliance upon systemic analgesics. Neuropathic pain is typically more difficult to manage and in contrast relies upon locally acting anesthetics and centrally acting antidepressant and anti-convulsant medications, along with biopsychosocial treatment and systemic analgesics. Future research regarding pain in head and neck cancer patients should consider neuropathic and nociceptive pain-related complaints along with quantitative sensory testing to confirm neuropathic pain. In clinical practice, clinicians should consider contemporary management for both nociceptive and neuropathic pain in head and neck cancer patients.Pain experienced during radiation therapy for head and neck cancer is common. Neuropathic pain descriptors were chosen by 73% of patients and a linear trend was seen in number of neuropathic and nocicpetive descriptors chosen by pateints during therapy. Pain was common despite ongoing pain management during therapy. This study shows that pain during radiation therapy have both nocicpetive and neeuropathic qualities.The authors declare that they have no competing interests.JE reviewed study data and drafted the manuscript. YOK performed the statistical analysis. DJW conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors contributed to and approved the final manuscript.


We estimated these proportions epidemiologically from the nationwide Swedish Family-Cancer Database on 9.6 million individuals. Colorectal adenocarcinomas were retrieved from the Cancer Registry covering years 1958–1996. Standardized incidence ratios (SIRs) were calculated for offspring (aged less than 62 years) when their parent had colorectal adenocarcinoma. In 9.82% of all families, an offspring and a parent were affected, giving a population attributable proportion of 4.91% and a familial SIR of 2.00. When offspring and parents shared the anatomic site, the SIR was 2.32 for proximal and 2.00 for distal CRC. When offspring were diagnosed before age 40 years and parents before age 50 years, the SIR was 25.72 for familial proximal CRC. In older age groups familial risks did not differ between proximal and distal CRC. Familial risks were increased also for endometrial, small intestinal and gastric cancers, manifestations in HNPCC. Depending on which assumptions were made, HNPCC was calculated to account for 20 to 50% of familial CRC, corresponding to 1 or 2.5% of all CRC among 0–61-year-old individuals. © 2001 Cancer Research Campaign


Human parvovirus B19 (B19) infection a transient reduction in blood haemoglobin concentration is induced, due to a 5-7 day cessation of red cell production. This can precipitate severe anaemia in subjects with a range of pre-existing conditions. Of the disease markers that occur during B19 infection, high IgM levels occur closest in time to the maximum reduction in haemoglobin concentration. Previous studies of the contribution of B19 to severe anaemia among young children in Africa have yielded varied results. This retrospective case/control study seeks to ascertain the proportion of severe anaemia cases precipitated by B19 among young children admitted to a Kenyan district hospital.During acute Archival blood samples from 264 children under 6 years with severe anaemia admitted to a Kenyan District Hospital, between 1999 and 2004, and 264 matched controls, were tested for B19 IgM by Enzyme Immunosorbent Assay and 198 of these pairs were tested for B19 DNA by PCR. 536 samples were also tested for the presence of B19 IgG.7 (2.7%) cases and 0 (0%) controls had high B19 IgM levels  (McNemar's exact test p = 0.01563), indicating a significant association with severe anaemia. The majority of strongly IgM positive cases occurred in 2003.95 , McNemar's exact test p = 0.3018. There was no significant difference between cases and controls in the B19 IgG (35 (14.8%) vs 32 (13.6%)), OR = 1.103 , or the detection of the B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2 .10/264 (3.7%) cases compared to 5/264 (1.9%) controls tested positive for B19 IgM. This difference was not statistically significant, odds ratio (OR) = 2.00  of cases of severe anaemia in the population of children admitted to KDH were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data that shows that less than 15% of children in the study were exposed to B19, a figure much lower than reported in other tropical areas. P falciparum infection, iron deficiency, protein-energy malnutrition, haemoglobinopathies and other infections including HIV , McNemar's exact test p = 0.3018. Prevalence of B19 IgG increased with age , or the detection of B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2   compared to 5/264 (1.9%) in the controls. This difference was not statistically significant, odds ratio (OR) = 2.00  were all (n = 7) found among the cases, with none (n = 0) among the controls. The association between these high IgMs and severe anaemia was statistically significant with McNemar's exact two-tailed p = 0.0153. The odds ratio for this effect is inestimable as the numbers of controls with high IgM OD = 0.P falciparum but the control was not, and 38 (30.9%) pairs where the control was positive for P falciparum but the case was not. Thus P falciparum was significantly associated with severe anaemia ).Among the matched pairs in the study, 5 cases and 2 controls had a diagnosis of sickle cell disease. One of these (a control) was B19 IgM positive. None of the children with sickle cell disease were B19 PCR positive. Results of blood slide microscopy for malaria parasites were available for 256 of the matched pairs. Of these there were 123 discordant pairs: 85 (69.1%) pairs where the case was positive for P. falciparum parasitaemia was not significantly associated with B19 IgM in either the cases or controls (Fisher's exact test 2-tailed p = 0.7296 vs p = .0.6826). There was no significant association between severe anaemia and dual  positive samples (6 (2.3%) cases as compared with 3 (1.2%) controls. Odds ratio = 2.00.The incidence of B19 infection varied between years, with an increase of positive B19 IgM results in the year 2003. In matched pairs from that year 7 (13.0%) of severely anaemic children tested were positive for B19 IgM. 6 of the 7 high IgM results occurred in 2003 . This lower rate of infection in Kilifi is also demonstrated in the IgG results, which show that of these Kenyan children ≤ 6 years only 14.2% have previously had a B19 infection as compared to 63% of children ≤ 5 years in Wosera district, PNG. Possible reasons include differences in climate, socio - economic factors and genetic factors. Furthermore the differences in the type of samples used should also be taken into account. In this study the full range of hospital admissions included all seriously ill children with a range of clinical problems, while in PNG samples came from children with 'clinical malaria' defined as fever with no obvious respiratory cause. It is likely that the selection of children with a history of fever increased the number of acute B19 infections in the PNG samples.The lower than expected frequency of infections among the present study population meant that the analysis did not have the power to find a significant difference between IgM positive rates in cases and controls with the found odds ratio of 2. Thus, while there are more positives among cases for overall IgM+ and PCR+ these differences did not reach statistical significance. However in spite of the low numbers of B19 infections, a high B19 IgM level  is significantly associated with severe anaemia. High IgM levels are most likely to be measured around the time of haemoglobin reduction, and therefore have the strongest association with severe anaemia. This association suggests that in other places where B19 infections are more common among young children (e.g. Eritrea) , the conP. falciparum infection is shown to be a cause of severe anaemia in this area, as has been documented previously [P. Falciparum parasitaemia in children presenting with severe anaemia.In the current study eviously , howeverHigh B19 IgM levels were significantly associated with severe anaemia, being found only among the cases. This suggests that at least 2.7% of cases of severe anaemia in the population of children admitted to Kilifi District Hospital were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data which shows that less than 15% of children in the study had contracted B19, a figure much lower than reported in other tropical areas.Biotrin International Ltd donated the Parvovirus B19 EIA kits, otherwise the authors declare no competing interests.JW, NG and JT performed the nucleic acid amplification and quantitation. JW and NG performed the serology. JW, YC, NP, TW and CN participated in research design, data analysis and drafting of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/10/88/prepub


Plasmodium vivax are restricted to samples collected from infected persons or primates, because this parasite cannot be maintained in in vitro cultures. Contamination of P. vivax isolates with host leukocytes and platelets is detrimental to a range of ex vivo and molecular investigations. Easy-to-produce CF11 cellulose filters have recently provided us with an inexpensive method for the removal of leukocytes and platelets. This contrasted with previous reports of unacceptably high levels of infected red blood cell (IRBC) retention by CF11. The aims of this study were to compare the ability of CF11 cellulose filters and the commercial filter Plasmodipur at removing leukocyte and platelet, and to investigate the retention of P. vivax IRBCs by CF11 cellulose filtration.Investigations of 3 per μl [95%CI 5.2–13.5] to 0.01 × 103 [95%CI 0.01–0.03]. The CF11 was particularly effective at removing neutrophils. CF11 treatment also reduced initial platelet counts from 211.6 × 103 per μl [95%CI 107.5–315.7] to 0.8 × 103 per μl [95%CI -0.7–2.2]. Analysis of 30 P. vivax blood samples before and after CF11 filtration showed only a minor loss in parasitaemia . Stage specific retention of P. vivax IRBCs was not observed.Side-by-side comparison of six leukocyte removal methods using blood samples from five healthy donor showed that CF11 filtration reduced the mean initial leukocyte counts from 9.4 × 10P. vivax-infected erythrocytes from field isolates.CF11 filtration is the most cost and time efficient method for the production of leukocyte- and platelet-free  Plasmodium vivax still relies on the use of infected blood samples collected from patients or experimentally infected simians, because it is not yet possible to continuously culture this parasite.The emergence of drug resistance and the ex vivo investigations to 0.01 × 103 [95%CI 0.01–0.03] and 0.7 × 103 per μl [95%CI 0.4–1.8] respectively  (p = 0.02). Only by pre-processing the blood sample with Lymphoprep prior to Plasmodipur filtration was it possible to reduce the mean leukocyte (0.3 × 103 per μl [95%CI -1.1–1.8]) and platelet (0.0 × 103 per μl) contamination to the same levels as that obtained by CF11 filtration. However, pre-treatment with Lymphoprep adds another 50 mins and a further ~8–9 USD to procedure, thus negating the benefits of the relatively speedier Plasmodipur filtration. It was interesting to note that the composition of the contaminating leukocytes in the suspension obtained after Lymphoprep/Plasmodipur or CF11 filtration differed greatly. Leukocyte contamination in the Lymphoprep/Plamodipur filtrate was predominantly neutrophils (98%) with the remainder made up of lymphocytes and basophils/monocytes . The magnitude of IRBC loss was much less than the major losses previously reported for CF11 filtration, namely from a starting parasitaemia of 0.37% to 0.18% in the filtrate for one sample and 0.43% to 0.01% for the other, representing a 52% and 98% reduction in parasitaemia respectively  (p = 0.06)  Figure . This isnot noted,13,15, a®)It should be noted that equally satisfactory removal of leukocytes and platelets, with little loss of parasites, were obtained when the PBS solution was used to wash and resuspend the blood and the CF11 columns was replaced by RPMI or McCoy's 5A medium (GIBCOP. vivax clinical isolates. The small, non stage specific, reduction in parasitaemia due to CF11 filtration has done little to hamper its application to a range of recent P. vivax studies [P. vivax transcriptome[P. vivax retention by CF11 [Custom-made CF11 filtration provides a cost effective method for the removal of leukocytes from  studies -14,16, n by CF11  where thAn additional benefit of WBC and platelet filtration, irrespective of the method chosen, is that it aids in the microscopic examination of thick films. Thick films made from filtered isolates produce clear 'noise-free' thick films Figure . This maThe authors declare that they have no competing interests.KS, SK and RS helped design this study, optimized and conducted the experiments, microscopy, and drafted the manuscript. UL and MLL coordinated the field studies, sample collection, and provided intellectual guidance though out this study. BR conceived the study, designed and participated in the experiments, was the cross check microscopist, responsible for photomicrographs and figure production, and initial drafting of the manuscript. GS provided invaluable intellectual input through out the study and significant contributions to the production of the final manuscript. APP and FN coordinated the clinical support and ethical approval. LR and FN jointly directed the study as a whole, providing major intellectual guidance though out this study and during manuscript preparation. All authors read and approved the final manuscript.


We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9%  with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9%  with 10.1% CR. Median survival was similar in the two arms at 6.4 months  and 5.8 months  respectively. Survival at 1 year was 9.9%  and 8.9% . The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.