The increase in the burden of chronic diseases linked to the nutrition transition and associated dietary and lifestyle changes is of growing concern in south and east Mediterranean countries and adolescents are at the forefront of these changes. This study assessed dietary intake and association with socio-economic factors and health outcomes among adolescents in Tunisia.th and 95th percentile defined overweight and obesity. Waist Circumference (WC) assessed abdominal fat. High blood pressure was systolic (SBP) or diastolic blood pressure (DBP) ≥90th of the international reference for 15-17 y., and SBP/DBP ≥120/80 mm Hg for 18-19 y.Cross-sectional survey (year 2005); 1019 subjects 15-19 y. from a clustered random sample. Dietary intake was assessed by a validated semi-quantitative frequency questionnaire (134 items) as was physical activity; the Diet Quality Index International measured diet quality; dietary patterns were derived by multiple correspondence analysis from intakes of 43 food groups. Body Mass Index (BMI) ≥85nd vs. 1st tertile: Prevalence Odds-Ratio (POR) = 4.0[1.7-9.3], 3rd vs. 1st: POR = 3.3[1.3-8.7]) and a higher WC. Adjusting also for BMI and WC, among females, it was associated with decreased prevalence of high blood pressure .Energy intake levels were quite high, especially for females. The macro-nutrient structure was close to recommendations but only 38% had a satisfactory diet quality. A main traditional to modern dietary gradient, linked to urbanisation and increased economic level, featured an increasing consumption of white bread, dairy products, sugars, added fats and fruits and decreasing consumption of oils, grains, legumes and vegetables; regarding nutrients this modern diet score featured a decreasing relationship with total fat and an increase of calcium intake, but with an increase of energy, sugars and saturated fat, while vitamin C, potassium and fibre decreased. Adjusted for age, energy and physical activity, this modern pattern was associated with increased overweight in males (2The dietary intake contrasts among Tunisian adolescents, linked to socio-economic differentials are characteristic of a nutrition transition situation. The observed gradient of modernisation of dietary intake features associations with several nutrients involving a higher risk of chronic diseases but might have not only negative characteristics regarding health outcomes. The prevalence of overweight among children and adolescents is increasing worldwide -3 while th out of 177 on the Human Development Index composite scale in 2005 ). In adjusted analyses, the slight association with sex persisted to a certain extent. Regional differences were still strong  but the urban vs. rural contrast was reduced to only +4.8[1.1-8.5] (P = 0.012). A strong gradient of "modernisation" of the diet with increasing economic level of the household was still observed . The characteristics of the father were no longer associated, but there remained a mild independent trend towards a more modern diet among adolescents whose mother worked outside the home (P = 0.043), had a higher education level (P = 0.0013) and those registered at school (P = 0.030).Meat-fish diet score: in unadjusted associations no differences were observed between the sexes, and only marginal differences for age, with older subjects scoring somewhat higher. Only the Middle Eastern Region (vs. Middle Western) scored higher (+15.0 [10.3-19.7]) and there was no urban vs. rural difference. As for the economic level of the household, the main difference was in the intermediate category (vs. lower) (+6.5 [2.6-10.3]). The only other marginally significant difference was observed among adolescents whose mother worked outside the home (-3.5 [-7.3-0.3]). Factors related to the father were not associated with the meat-fish diet score. After adjustment, there was still no independent association with sex and the older subjects scored slightly higher. The sharp contrast between the Middle Eastern and the Middle Western Regions remained unchanged, as did the milder one between the middle and low economic level. A mother working outside the home with a higher education level resulted in somewhat lower scores, while attending school (vs. not) was associated with a higher meat-fish score.Anthropometry: the nutritional status of adolescents in the study area featured a mean BMI of 21.4 ± 0.1 kg/m2, , the prevalence of overweight was 18.9% ± 1.5  and obesity 4.3% ± 1.0 . Mean WC was 74.2 ± 0.4 cm .For both genders, no association was observed between tertiles of energy intake and BMI nor overweight, while for abdominal fat accumulation, only for boys was there a monotonous increase in mean WC with tertiles of energy intake, whether raw (P = 0.001) or adjusted (P = 0.021), (detailed data not shown).nd and 3rd tertiles ; these associations were minimally confounded by age, total energy intake or physical activity measures . Adjustment for socio-economic factors changed the estimates somewhat more . In females, the only association observed with anthropometry, was with abdominal fat accumulation, those in the 3rd vs. 1st tertile of the modern score featuring a somewhat higher mean WC in unadjusted analysis, but the strength of the association was further reduced in adjusted analyses. Regarding the meat-fish dietary pattern score, a higher mean BMI and WC was observed in males in the 3rd tertile, either adjusted of not. No obvious relationship was observed in females.In males, associations between the modern dietary pattern score and anthropometric measures of total and abdominal fat accumulation showed that BMI, prevalence of overweight and WC increased with modernisation of the diet Table , though Blood pressure: overall mean systolic BP (mm Hg) was 112.8 ± 0.4 , and diastolic 67.2 ± 0.4 . Prevalence of high blood pressure was 37.4% ± 1.8  and that of hypertension 5.2%±1.0 .nd vs. 1st tertile POR = 2.1[1.2-3.5], 3rd vs. 1st tertile POR = 1.7[1.0-2.9]).As for associations between levels of energy intake (in tertiles) and BP (detailed data not shown), none were observed for boys. Among females after adjustment there was an increase in levels of high blood pressure with tertiles energy intake ; this association was minimally reduced by adjustment for age, total energy intake or physical activity measures  but confidence intervals were widened by adjustment on socio-economic factors . Was also observed a lower prevalence of hypertension in the highest tertile of the "modern" dietary pattern .As for association with dietary patterns: - i) in males, except for the mild bell-shaped association with diastolic blood pressure and hypertension, no straightforward associations were observed between BP and the modern diet score. For the meat-fish diet score, although before adjustment for energy intake, BMI and WC, there was an increase in diastolic blood pressure, no major associations were observed either Table . - ii) fThe present study aimed at assessing dietary intake and patterns, as well as associations with socio-economic cofactors and health outcomes such as overall nutritional status and blood pressure, among Tunisian adolescents.As for overall energy intake, within the limits of the estimation of dietary intake using a semi-quantitative food frequency questionnaire, we found high overall intake by both males and females, largely exceeding the requirements based on their physical expenditure level, and more so in females than in males. Indeed, we found close average energy intake levels between boys and girls, contrary to what has been observed over the last decades in Europe, where, whatever the methodology employed, females always displayed much lower energy intakes than males . In thisThough not far from recommendations, on average the diet was a little high in fat as a % of energy, as is common in European Mediterranean countries, with a favourable ratio of unsaturated fats due to the consumption of olive oil . As the Concerning food based descriptive analysis of dietary intake by computation of dietary patterns, the main dimension underlying food consumption data was found to be a traditional to modern gradient, characterised from the food point of view by a linear decrease in consumption of long-established foods such as vegetable oil, cereals, grains, legumes and vegetables and an increase in foods made more widely available in the last decades such as white bread, dairy products, sugars and confectionery, added fats, fried potatoes and fruits. It is of course always difficult from a methodological standpoint to discuss longitudinal inferences based on cross sectional data. But anyway, this finding is in line with a chronological food transition process  that wouA second gradient, though of less importance, was observed, characterised by a monotonous and increasing relationship with energy, meat and fish consumption and somewhat decreasing with white bread, milk, sugars and sweet beverages and added fats. Interestingly, it revealed another path to a modified diet accompanying economic improvement, which yielded a better quality diet (DQI-I) for the last tertile than the modernised diet, with still a better ratio of unsaturated to saturated fats due to an increase in olive oil consumption, despite its richness in animal proteins; however, it also featured an excess of energy. It is apparently rather specific to the coastal Middle Eastern Region in Tunisia and to intermediate economic level households, without much independent effect of other socio-economic cofactors.nd tertile). It is to be noted that the association was somewhat reduced from a statistical point of view by adjustment on socio-economic factors; nevertheless, it is debatable whether this third type of adjusted estimate is the relevant one for assessing association of diet patterns with health outcomes. Indeed, some authors do not adjust for socio-economic factors when assessing relationship between health outcomes and dietary patterns, which is coherent with a conceptual framework such as that presented in Figure Even after adjustment , with the exception of WC for boys, there was no straightforward relationship between anthropometry and energy intake or imbalance in neither gender. However, such a null association is rather frequently observed in either cross-sectional or even prospective studies. Underreporting, methodological errors, insufficient measurement precision or accuracy of energy intake and expenditure or dieting have successively been invoked ,61. On tNot so many studies have tried to distinguish dietary patterns in adolescents in relation with their health status in industrialised countries ,74-78 anAs for the strong and weak points of the study, regarding design and sampling, the cross-sectional design with retrospective estimates of exposure has known limitations when trying to interpret observed associations as causal. The study carried out in 2005 is quite recent but given the rapid pace of societal and socio-economic changes in emerging countries such as Tunisia it cannot be ruled out that further changes may have occurred since. The stratified, clustered random sample of 1019 subjects, although not national, was representative of three regions that feature a panel of the socio-economic and nutritional situations in Tunisia, as assessed by observed distributions of socio-economic factors and nutritional status indicators with reference to a national survey ; there wAlthough widely used in other fields, the MCA technique itself has previously been rarely used for computation of dietary patterns compared to PCA or factor analysis, or only with dichotomous coding of food group intakes ,42. In oRegarding measurements, assessment of dietary intake by a retrospective frequency questionnaire does raise a number of concerns  especialA specific strength of the study was to feature, through a validated questionnaire, a direct and detailed assessment of physical activity and thus control of confounding related to this dimension.Regarding assessment of overweight and obesity, there are, indeed, a number of issues regarding the choice of international references and/or the use of a national reference -88. Our If the nutrient related hypotheses put forward to explain decrease of BP with modernisation of the diet among girls are coherent with the observed associations, some amount of confounding by factors not taken into account in the study cannot be ruled out. Indeed, the modernisation of the diet could be a correlate of a modernised lifestyle which, all the more for girls in the Tunisian context, could have both indirect effects through dietary intake and physical activity, but also, direct effects on measured health outcomes. It should then be of interest to assess dimensions such as health related quality of life, perceived stress or family psychosocial factors ,90. MoreThe present study is one of the few providing evidence regarding transition related dietary and health issues among adolescents from emerging North African or Middle East Arab countries, of which Tunisia is emblematic: indeed, although one must be careful not to overstate similarities between these countries, especially from a development point of view, their youth do share common consequences of globalization and related overall and rapid economic and societal changes as well as a number of common socio-cultural issues.The analysis of the diet of these adolescents revealed a main pattern of modernisation along with urbanisation and regional socio-economic development leading to a more varied and adequate diet that prevents nutrient deficiencies. A favourable effect on BP in girls likely linked to more dairy consumption was also observed, although some amount of confusion by psycho-social factors cannot be entirely ruled out; nevertheless, this association points out that one should perhaps avoid systematically shedding a negative light on a modernised diet vs. an idealised traditional one. However, this modernisation gradient was also correlated with an excess of energy and nutrients such as saturated fat involving a higher risk of chronic diseases, while protective antioxidant micronutrients like vitamin C decreased notably.The root causes of dietary changes and the nutrition transition are at a very macro level linked to global socio-economic and societal changes; nevertheless, interventions aimed at adolescents or their parents ,92 to prThe authors declare that they have no competing interests.HAS designed the study, supervised data collection, contributed to data analysis and drafted the manuscript; PT planned and performed data analyses, contributed to interpretation of the results and to writing the manuscript; JEA contributed to the interpretation of the food consumption data and helped edit the manuscript; SED and EL helped with data management and interpretation of food consumption data; FD and NA contributed to the study design and revision of the manuscript; HBR and BM were involved in all steps, from the design of the study to the revision of the manuscript. All authors read and approved the manuscript.


Staphylococcus aureus (SA) strains producing staphylococcal enterotoxins SEA, SEB, SEC, SED, and TSST-1 and nonproducing ones. In the group of the total 28 of the patients with erythrodermia the presence of SA was confirmed in 24 cases. The total of 14 strains of SA excreted enterotoxins SEA, SEC, SED, and TSST-1. We did not observe that strains producing mentioned superantigens were less susceptible to AMPs . The opposite situation was observed in conventional antibiotics. SA strains excreting tested superantigens had higher MICs and MBCs than nonproducing ones. The interesting finding considering the high efficacy of AMPs, against all examined strains of SA, makes them attractive candidates for therapeutic implication. Superantigens are proteins comprising a group of molecules produced by various microorganisms. They are involved in pathogenesis of several human diseases. The aim of the study was the comparison of susceptibility to antibiotics and antimicrobial peptides (AMPs) of  Superantigens are proteins comprising a group of molecules produced by various microorganisms, such as bacteria , fungi (yeasts), and viruses. They are involved in the pathogenesis of several human diseases  . SuperanStaphylococcus aureus (SA) [2) on the skin of atopic dermatitis patients is significantly higher than on that of healthy population [β-defensin), as well as the pH shifted to alkaline region (7-8), fibronectin receptors exposure of adhesin-binding cell wall of SA, and destruction of the skin barrier by substances excreted by these germs are responsible for SA skin colonization in AD [ Some 80 to 100 percent of atopic dermatitis (AD) patients have skin colonization with eus (SA) . It has pulation . Suppreson in AD –8. The aggravating role of SA superantigens is well known in AD but has not been well documented in psoriasis. There are single reports concerning correlation between the severity of AD and psoriasis and enterotoxin production of isolated SA strains . There are single reports confirming the relationship between erythrodermic cutaneous T-cell lymphoma (CTCL) and superantigens producing SA colonization . It has Bering in mind that the enhanced resistance of bacteria to conventional antibiotics is a serious problem in present-day healthcare, the development of novel antimicrobial therapies, such as those based on various antimicrobial peptides, seems to be reasonable. β-defensin-2 (HBD-2) and -3 (HBD-3) or the cathelicidin LL-37 [Humans express a blend of antimicrobial peptides (AMPs), which are found at biological boundaries prone to infection. One of the most important innate defense mechanisms of the human skin is the production of AMPs. They are produced mainly by keratinocytes in the stratum corneum, neutrophils, or by sweat glands and are either expressed constitutively like RNase 7, psoriasin, or dermcidin or after an inflammatory stimulus like in LL-37 . AMPs kiin LL-37 . Actuallin LL-37 . Expressin LL-37 . 2, protegrin 1, tachyplesin 3, temporin A, and uperin 3.6).Herein, we investigated SA colonization in patients with erythrodermia (a skin inflammation of more than 90% of body surface) that developed in the course of psoriasis, atopic dermatitis, cutaneous T-cell lymphoma, or Sezary Syndrome (SS) , 18. The2, protegrin 1, tachyplesin 3, temporin A, and uperin 3.6) included in the study were synthesized manually in a microwave reactor by the solid-phase method using the 9-fluorenylmethoxycarbonyl chemistry (Fmoc) [Peptides  , 20. TheBecton Dickinson, Germany) using standard microbiological procedures. SA was identified on the basis of colony morphology, production of catalase, and positive slide coagulation test (Staphaurex and Biomerieux). The susceptibility to antibiotics was determined by disk diffusion method as recommended by CLSI  guidelines. The following antimicrobials were tested: penicillin, oxacillin, erythromycin, doxycycline, clindamycin, rifampicin, chloramphenicol, linezolid, daptomycin, tigecycline, and ciprofloxacin . The susceptibility tests were performed on the Mueller-Hinton II (Becton Dickinson). The results obtained by disk diffusion were compared to those of the broth microdilution in the case of linezolid, daptomycin, tigecycline, rifampicin, chloramphenicol, erythromycin, and clindamycin.Twenty-eight patients with erythrodermia, hospitalized at the Department of Dermatology, Venereology, and Allergology from January 2007 to October 2008, were enrolled in the study. From each patient, skin swabs were taken. All samples were cultured on the Columbia agar plates  was used for the detection of staphylococcal enterotoxins A, B, C, and D in culture by reversed passive latex agglutination. Clinical strains of SA were incubated in Tryptone Soy Broth (Becton Dickinson) and incubated at 37°C for 18–24 hours, with shaking on a water bath. After growth, they were centrifuged at 900 g for 20 minutes at 4°C, and the supernatants were used as the test sample. Latex sensitised with antienterotoxin A, B, C, or D was added to filter-sterilized supernatants on V-well microtiter plates . A visible agglutination on the bottom of the well was considered as a positive result.A staphylococcal enterotoxin test kit  was used for the detection of a staphylococcal toxic shock syndrome toxin in culture by reversed passive latex agglutination. Clinical strains of S. aureus were incubated in a brain-heart infusion broth (Becton Dickinson) and incubated at 37°C for 18–24 hours, with shaking on a water bath. After growth, they were centrifuged at 900 g for 20 minutes at 4°C, and the supernatants were used as the test sample. Latex sensitized with antitoxin was added to filter-sterilized supernatants on V-well microtiter plates (Sigma-Aldrich). A visible agglutination on the bottom of the well was considered as a positive result.A staphylococcal toxic shock syndrome toxin kit . MIC was determined using a microbroth dilution method with the Mueller Hinton Broth II (MHB II) (Becton Dickinson) and initial inoculums of 5 × 105 CFU/mL. Polypropylene 96-well plates (Sigma-Aldrich) were incubated for 18 h at 37°C. MIC was taken as the lowest drug concentration at which a noticeable growth was inhibited. MBC was taken as the lowest concentration of each drug that resulted in more than 99.9% reduction of the initial inoculums. The experiments were performed in triplicate.A total number of 24 SA strains were obtained from patients with erythrodermia and 3 reference SA ones from the American Type Culture Collection: 6538P ATCC, 9144 ATCC, and 25923 ATCC  the presence of SA was confirmed in 24 cases. Negative cultures for SA were noticed in three patients with psoriasis.A total number of 14 SA strains excreted enterotoxins SEA (8 strains), SEC (3 strains), and/or SED (5 strains) and only one TSST-1 in the group of 24. Intermediate results (+/−) were considered as negative. In the group of 9 patients with AD, the superantigen-producing strains were detected in 6 patients, in the group of 6 patients with CTCL—in 3 cases and in 8 patients with psoriasis—in 3 cases. SA strains isolated from two patients with SS did not produce the above-mentioned superantigens.The susceptibility to antibiotics determined by the disk diffusion method and broth microdilution gave identical results (data not shown). The antibiotics used in the study, rifampicin, tigecyline, vancomycin, daptomycin, ciprofloxacin, chloramphenicol, clindamycin, and erythromycin, exhibited diverse activities against clinical isolates of SA. The rifampicin, tigecycline, vancomycin, and daptomycin MICs values, which were the lowest among the tested antibiotics, varied between 1 and 4 mg/L. The other ones were higher than the tested antimicrobial peptides: tachyplesin 3, lipopeptide, and protegrin 1 were extremely effective against all the tested bacterial strains ; see We did not notice that strains producing tested superantigens  were less susceptible to AMPs than nonproducing ones. The opposite situation was observed in conventional antibiotics. SA strains excreting those superantigens had higher MICs and MBCs Figures Bacterial superantigens, which stimulate clonal expansion of T-cells by mechanisms involving specific HLA molecules, have also been hypothesized to cause inflammatory skin diseases . The mecStaphylococcus and Streptococcus have been reported to exacerbate psoriasis [There are many studies that explain the effect of SA on AD . Most SAsoriasis , 23. Thesoriasis . The assβ-lactams which target cell wall development in bacteria and are the basis for the treatment of skin and soft-tissue infections could even increase the production of toxins [We found that 24 out of 28 erythrodermic patients had a staphylococcal culture positive from the skin, and tested superantigens were detected in SA strains isolated from 14 patients. The purpose of our study was to investigate whether or not the strains producing SEA, SEC, SED, and TSST-1 are more resistant to conventional antibiotics and AMPs. Considering susceptibility to antimicrobial peptides, we did not notice any significant differences between strains producing tested superantigens and nonproducing strains. The opposite situation was noticed in susceptibility to conventional antibiotics. The SA strains producing specified superantigens had higher MICs and MBCs as compared to the nonproducing ones. Especially alarming is the higher resistance of those strains to macrolides and lincosamides which could not only kill bacteria and diminish the rate of colonization but also inhibit their superantigen and toxin production . One stuf toxins . SA straOver 50% incidence of production of tested superantigens in strains from AD patients is in accordance with previous studies .Several studies on the effect of antimicrobial treatment on the colonization with SA and the severity of inflammation gave conflicting results. In several open or double-blind placebo-controlled trials, topical or systemic antibiotics were able to reduce colonization density and led to a partial improvement of skin lesions –29. On tFrom a clinical point of view, our study has several implications. Considering that erythrodermic patients are frequently treated with various antibiotics, the question may be raised whether excessive use of antibiotics and induction of resistance are associated with cross-resistance to AMPs. We found no evidence for the development of the AMPs resistance in relation to antibiotic susceptibility, likely reflecting the fact that the mode of action of the antibiotics investigated herein is not shared with AMPs. An interesting finding of the high efficacy of AMPs, especially lipopeptides, against all tested strains of SA makes them attractive candidates for therapeutic application.The authors declare that they have no conflict of interests.


To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects.The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery.P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting.Tramadol group had significantly lower pain scores (Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects.Registration No: IRCT201103255764N2 Postoperative pain has not only a pathophysiologic impact but also affects the quality of patients’ lives. Improved pain management might therefore speed up recovery and rehabilitation and consequently decrease the time of hospitalization . SurgeryTonsillectomy is a common surgery in children and post-tonsillectomy pain is an important concern. Duration and severity of pain depend on the surgical technique, antibiotic and corticosteroid use, preemptive and postoperative pain management, and patient’s perception of pain -9. ThereKetamine is an intravenous anesthetic from phencyclidin family, which because of its antagonist effects on N methyl-D-aspartate receptors  has regulatory influence on central sensitization and opium resistance. It can also band with mu receptors in the spinal cord and brain and cause analgesia. Ketamine can be utilized intravenously, intramuscularly, epidurally, rectally, and nasaly ,16. SeveTramadol is an opium agonist that mostly effects mu receptors, and in smaller extent kappa and sigma receptors, and like anti depressant drugs can inhibit serotonin and norepinephrine reuptake and cause analgesia ,12,18. ISeveral studies have confirmed the efficacy of tramadol and ketamine on post-tonsillectomy pain ,10-12,20http://irct.ir) as IRCT201103255764N2. Forty two patients were chosen for each group . A written consent was obtained from patients' parents.This randomized placebo-controlled clinical trial was carried out from March to September 2010 in Shahid Sadoughi Hospital, Yazd, Iran. After having received an approval from university institutional ethics committee, the study was registered in Iranian registry of clinical trials  20 minutes before the end of the surgery. Trial drugs were coded by an anesthetic technician and were provided in 2 cc syringes. During the operation 4-5 cc/kg/h Ringer was infused.All patients were in American Society of Anesthesiologists Physical Status Classification class I and II , with noBefore surgery, block randomization was performed according to age and sex of patients. Time of anesthesia and time of surgery were determined during surgery and inter-group differences were calculated. The first group (group A) was injected 0.5 mg/kg ketamine, the second group (group B) 2 mg/kg tramadol, and the third group (group C) 2 cc NaCl  at the bed and anterior fold of each tonsil (1 cc for each tonsil) by an anesthesiologist who was not aware of the type of the drugs. The selected doses were chosen based on previous studies ,10-19,21Following transfer to the ward, sedation and pain scores at 2, 4, 6, 8, and 12 hours were documented by an anesthesia resident using Ramsay  and CHEOAt the entrance to Ear, Nose, Throat (ENT) ward, 0.5cc/kg acetaminophen syrup was given. The time to the first request for analgesic and the time to first oral intake (liquid regimen) were documented. All data were analyzed by SPSS software, version 15  using ANOVA, Bonferroni correction, and Mann-Whitney U tests.We compared the analgesic effect of ketamine and tramadol to placebo on 126 children between 5 and 12 years old (42 patients in each group). One hundred forty-seven patients were approached, 15 patients did not meet the inclusion criteria and were excluded from the study, and 6 were excluded due to surgery duration of more than 1 hour, which amounted to 126 patients who were finally included . No signP = 0.035), and time to the beginning of liquid regimen   .P = 0.005)  . Five paP = 0.001). The heart rate in tramadol group was lower than in other groups during the whole post-operation period (except 5 and 10 minutes after arriving to recovery room). There were significant differences in heart rate between tramadol and other two groups (P = 0.001).There were no significant differences in SBP and DBP between groups before and during surgery. But, after surgery and during extubation tramadol group showed lower blood pressure level than other two groups  .P = 0.005), 6 (P = 0.008), and 12 (P < 0.001), with greater scores in ketamine group, but no significant differences were observed at hours 2 (P = 0.146) and 8 (P = 0.56). Ketamine and placebo groups, except at hour 2 (P = 0.009), showed no significant differences in the sedation scores. Tramadol and placebo groups also showed no significant differences in sedation scores. All three groups showed no differences in sedation scores during all times, except at hour 8 (P = 0.845).Mann-Whitney U test showed that sedation scores were significantly different between ketamine and tramadol group at hours 4 (P = 0.005).Prevalence of vomiting was 42.9% in ketamine group, 33.3% in tramadol group, and 38.09% in placebo group, which did not reach significance. Hallucinations were observed only in ketamine group, with the prevalence of 11.9% (This study found that peritonsillar infiltration of tramadol before tonsillectomy more efficiently decreased post-tonsillectomy pain than ketamine, with no complications. It also decreased analgesic consumption and the time to the beginning of oral liquid diet, while ketamine caused hallucinations and did not have the efficacy of tramadol in pain management and hemodynamic stabilization effects. We used 0.5 mg/kg ketamine and 2 mg/kg tramadol, which has been reported to be an effective and safe dose ,18,19,25Pain following tonsillectomy is one of the most important complaints and has several unwanted consequences such as excessive use of analgesics, longer period of hospitalization, intolerance to diet, which can lead to nutritional problems, and subsequently poorer quality of life -12.All analgesic methods have some potential drawbacks. Opioids can cause postoperative respiratory complications and sedation, whereas nonsteroidal anti-inflammatory drugs increase the risk of bleeding, which might require repeated surgeries to control homeostasis ,10,12,25We found that tramadol had significantly lower pain scores than other groups at all time points, which is in agreement with previous studies ,12,19. KIn our study, ketamine decreased the pain in the hour 12, which has been observed in other studies as well ,11. A prIn the ward, the time to first dose of analgesic request was longer in tramadol group than in the other two groups. This value was similar in tramadol group in two other studies ,12. AddiIn our study, tramadol group had significantly shorter time to the first liquid uptake than ketamine and placebo groups. These results, which are in agreement with other studies ,12, can Other studies observed no significant differences in mean arterial pressure and pain relief between ketamine and placebo groups ,11,16,17We also evaluated the sedation level using RAMSAY scale while patients were in the ward. In the recovery room, the scores were 3 of 5 in all groups; but by the time when the sedation scores decreased in all groups, these results were similar to other studies ,11. It w2O, and insistence of parents to start oral nutrition sooner than recommended.There were no significant differences in nausea and vomiting incidence between the three groups in our study but it was higher than in similar studies ,10. We uOther studies found no cases of hallucinations, night terrors, or sleep disturbances caused by ketamine ,11. HoweWe conclude that peritonsillar infiltration of tramadol before operation can decrease post tonsillectomy pain efficiently without any hemodynamic instability, sedation, or hallucinations. It can also decrease analgesic consumption and the time to the beginning of oral liquid diet, while ketamine can cause hallucinations and also does not have the efficacy of tramadol in pain management and hemodynamic stabilization effects. Therefore, we recommend the use of tramadol for management of post-tonsillectomy pain.


It is estimated that 30% of adults in the United States experience daily chronic pain. This results in a significant burden on the health care system, in particular primary care, and on the workplace. Chronic pain management with cognitive-behavioral psychological treatment is effective in reducing pain intensity and interference, health-related quality of life, mood, and return to work. However, the population of individuals with chronic pain far exceeds the population of therapists that can provide this care face-to-face. The use of tailored, Web-based interventions for the management of chronic pain could address limitations to access by virtue of its unlimited scalability.To examine the effects of a tailored Web-based chronic pain management program on subjective pain, activity and work interference, quality of life and health, and stress.Eligible participants accessed the online pain management program and informed consent via participating employer or health care benefit systems; program participants who completed baseline, 1-, and 6-month assessments were included in the study. Of the 645 participants, the mean age was 56.16 years (SD 12.83), most were female , and white . Frequent pain complaints were joint , back , and osteoarthritis . The online pain management program used evidence-based theories of cognitive behavioral intervention, motivational enhancement, and health behavior change to address self-management, coping, medical adherence, social support, comorbidities, and productivity. The program content was individually tailored on several relevant participant variables.P<.001). The magnitude of the 6-month effects were large. Trends for decreases in pain interference (36.8% reported moderate or enormous interference) reached significance at 6 months . The percentage of the sample reporting fair or poor quality of life decreased significantly from 20.6% at baseline to 16.5% at 6 months (P=.006).Both pain intensity , and unpleasantness  decreased significantly from baseline to 1-month  and 6-month  assessments (Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study. Further research is warranted to determine the significance and magnitude of the intervention’s effects in a randomized controlled trial. Recent estimates indicate that 30% of adults in the United States, or over 93 million people, experience chronic pain each day  resultinMultiple treatment guidelines exist for chronic pain management ,45,49-53To illustrate the magnitude of this problem, the following thought experiment is provided: It is known that approximately 93 million adults in the United States suffer from chronic pain . In ordeGiven that nearly 24 million adults are already seeking help for chronic pain online ,62, Web-Research has shown that Web-based treatment methods can be beneficial in managing chronic health conditions and promoting health ,69-73. AThe purpose of this study was to examine the naturalistic outcomes of a Web-based chronic pain management program that is structured around well-established chronic pain behavioral treatment guidelines ,14,70,78Care for your Pain digital health-coaching program) as part of their population health offerings and/or health benefit structure. The programs were offered at no additional cost to eligible individuals.Eligible participants were either employed by 1 of 37 participating US companies or a member of 1 of 18 participating US health care plans. Participating employers and health care plans purchased the Web-based, digital pain management program  received this message at the beginning of the program: “Before we get started, let’s make sure you’re in the right place. This program isn’t intended for people suffering from the following: acute pain, cancer pain, pelvic or abdominal pain. If you are experiencing these types of pain, contact your health care provider.” Those who continued their entry in this study were invited to complete an online baseline questionnaire that included 58 questions querying demographics, medical and psychological conditions, pain, general well-being, and daily functioning. This information was used to tailor program content and as a baseline measure of self-reported outcomes. Only very brief measures of each construct could be included to attenuate participant burden in this study, which did not compensate participants for the time they spent filling out assessment questionnaires.All participants who entered the pain management program and completed the 1-month and 6-month follow-up evaluations were included in analyses, and only the first enrollment into the pain program was used for analysis (some participants enrolled in the program multiple times). There were 645 unique participants who provided informed consent and participated in the program between October 10, 2007 and September 15, 2011. Participants did not receive any compensation for participating in this study.The Web-based pain management digital coaching program is a commercially available  behaviorally oriented program that uses proprietary technology to tailor the end-user experience such that it emulates an interaction with a behavioral pain management expert. The program uses patient self-report data and algorithms developed by expert clinicians to provide differing information and interventions based upon each participant’s unique pattern of responses to an interactive consultation that queries the end user regarding type, quality, and location of pain, mood, stress, sleep, current methods of managing pain, level of motivation, and self-efficacy to manage pain, and use/nonuse of prescription pain medications.The online pain management program integrates evidence-based theories of cognitive behavioral treatment ,79-85, cThe program provides ongoing feedback, usually 1 to 4 sentences long, between pages of the questionnaire to emulate a live coaching experience. Immediately after completing the baseline questionnaire, participants were provided with a tailored personal action plan and access to online pain management tools and library. The personal action plan consisted of 18 tailored Web pages. Regardless of the specific content given to a particular user, each user was provided with a welcome page see  and the Program content was delivered through text, images, videos, and interactive tools. During the study period, participants engaged with the program at-will via unlimited access to the action plan, online tools, and library to self-manage their chronic pain. Participants were invited by email to complete follow-up assessments 1 and 6 months after enrolling in the program. The program architecture and study design is displayed in Pain is commonly assessed in multiple domains including subjective pain intensity and unpleasantness ratings, interference with daily life, and ability to manage pain. We assessed each of these domains of pain experience. Pain intensity and unpleasantness over the past week were measured using a standard, well-validated 0-10 numeric rating scale with anchors at 0 (no pain or no unpleasantness) and 10 (extreme pain or extreme unpleasantness) ,97. To aCurrent level of motivation and confidence to manage pain were also measured using a 0-10 numeric rating scale with anchors at 0  and 10 (very motivated or very confident).Chronic conditions are frequently associated with lower life and health quality ratings. In this study, quality of health was measured using 1 item from the Centers for Disease Control and Prevention Health-Related Quality of Life 4-Item Measure (CDC HRQOL-4) ; qualityStress was measured at each time point with a single item: “How much stress do you feel in a typical day?” Responses were provided on a 4-point scale anchored with the following descriptions: none, not much, some, and a lot.Depression symptoms were measured at baseline using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D), Boston Form . We usedt tests (for continuous variables) or McNemar tests (for binary variables). Independent sample t tests (for continuous variables) or chi-square tests  were applied to examine the between-group differences on baseline data of (1) participants who improved at 1 or 6 months on pain ratings with participants who did not, and (2) participants who completed the 1- and 6-month evaluation with participants who did not. Any P value <.05 was considered statistically significant, unless otherwise noted. Each of the pairwise comparisons was tested at a significance level of .017 (.05/3). Effect sizes were reported, when applicable, using Cohen's d, and odds ratio (95% CI).Statistical analyses were conducted using SPSS for Windows version 18.0 . General linear model repeated measures (for continuous variables) or Cochran Q tests (for binary variables) were used to examine baseline, 1-, and 6-month outcomes. Post hoc pairwise tests were conducted by paired sample Descriptive characteristics of the sample are provided here to aid in the interpretation of the data . Participants resided in 38 of the 50 United States. The average participant age was 56 years (SD 12.83). Data on marital status and education level were not collected in this study. At baseline, participants had an average pain intensity rating of 5.30 out of 10 (SD 2.46), and an average unpleasantness rating of 5.43 out of 10 (SD 2.52) in which higher numbers reflect greater pain. Participants were motivated to manage their pain , and moderately confident that they could manage their pain  on the same 0-10 scale see .At study enrollment, 82.6% (285/345) of participants reported taking medication to relieve their pain, and 54.5% (351/644) of participants used medication every day or nearly every day in the past month. At baseline, participants had an average depression score of 2.70 (SD 2.45) out of a possible 10 points on the CES-D Boston Form . InformaWe compared program participants who completed the 1- and 6-month evaluations with participants who did not submit evaluations. Evaluation submitters and nonsubmitters did not differ in baseline demographic characteristics , duration of pain condition, quality of life and quality of health ratings, stress level, depression symptoms, the interference of pain in work and life, level of social support for pain, pain medication adherence, health care provider visits, emergency room visits, hospital admissions, or participation in psychological counseling or therapy for pain. Baseline pain intensity and pain unpleasantness ratings also did not differ between groups.P<.001, d=0.53). Evaluation submitters were also less likely to work outside the home . Evaluation submitters were more motivated to manage their pain at baseline,  and more confident that they could do so . Evaluation submitters also rated their overall quality of sleep higher than noncompleters . Finally, evaluation submitters were more likely than nonsubmitters to see their primary care physician , rheumatologist , or physical therapist  for pain, but less likely to see a chiropractor  for pain management. They were also more likely to take medication daily to relieve pain .Some other differences between evaluation submitters and nonsubmitters were identified. Evaluation submitters were, on average, nearly 7 years older than nonsubmitters  rated the program good or better given choices of poor, fair, good, very good, and excellent. Furthermore, most participants gave the program high usability ratings. Specifically, on a 5-point scale ranging from disagree (=1) to agree (=5), the percentage of participants who rated the program a 3 or better on the following items are as follows: 95.3% (602/632) read the information completely; 96.8% (609/629) found the information easy to read; 88.6% (551/622) found the information to be personally relevant; 93.8% (590/629) found the program easy to use; 90.5% (564/623) found the interactive exercises to be more helpful than simply reading a book or an article online; and 91.5% (558/610) experienced no technical difficulties while using the product.F2,1272 = 142.61, P<.001). The average baseline pain intensity rating was 5.30 (SD 2.46) out of a possible 10. Mean pain intensity decreased to 4.16 (SD 2.69) at 1 month and 3.72 (SD 2.73) at 6 months. Post hoc pairwise tests indicated a significant reduction in pain intensity at 1 month compared with baseline , and 6 months compared with 1 month , and 6 months compared with baseline .Participants’ pain intensity ratings decreased significantly following the intervention . The average pain unpleasantness ratings were 5.43 (SD 2.52) at baseline, 4.24 at 1 month (SD 2.81), and 3.78 at 6 months (SD 2.79). Post hoc pairwise tests indicated a significant reduction at 1 month compared with baseline , 6 months compared with 1 month , and 6 months compared with baseline .Pain unpleasantness ratings also decreased significantly following the intervention . Post hoc pairwise tests indicate a significant reduction at 6 months compared to 1 month (P=.004), and 6 months compared to baseline (P<.001).Pain interference was rated by participants as none, mild, moderate, or enormous. At baseline, 36.8% (231/627) of participants reported that they had moderate or enormous degrees of interference in daily life secondary to their pain. The proportion of participants reporting moderate or enormous pain interference decreased significantly following the intervention .At baseline, participants reported that they were quite motivated to manage their pain . Motivation to manage pain did not change significantly following the intervention .At baseline, participants reported that they were fairly confident that they could manage their pain . Confidence in managing pain did not change significantly following the intervention ; 18.1% at 1 month (113/625), and 16.5% (103 /625) at 6 months. Post hoc pairwise tests indicated a significant reduction at 6 months compared with baseline (P=.006).Participants rated their quality of life as corresponding to 1 of the following categories: poor, fair, good, very good, and excellent. One-fifth  of participants rated their quality of life as poor or fair at baseline. The proportion of participants rating their quality of life as fair or poor decreased following the intervention .Quality of health was rated using the same categories as quality of life. At baseline, 19.7% of participants reported their quality of health was fair or poor (123/624). This did not change significantly following the intervention .Participants rated their stress by selecting 1 of the following descriptors: none, not much, some, or a lot. At baseline, 18.9% of participants reported a lot of stress (63/334). This proportion decreased nonsignificantly over time .We tested to see if participation in additional online wellness programs beyond the pain program resulted in differential program outcomes. None of the group  by time effects were significant , pain duration, motivation to manage pain, type of health care providers treating their pain, pain medication adherence, or level of social support for pain. Characteristics that distinguished treatment responders from nonresponders are reported in In this study, we examined the longitudinal effects of a tailored Web-based chronic pain management program on multiple dimensions of pain experience , motivation to manage pain, confidence in ability to manage pain, quality of life and health, and stress among US adult employees and health care plan members who self-reported chronic pain and completed 1- and 6-month follow-up evaluations. Our main findings suggest that the tailored online chronic pain management program exerts significant beneficial effects on pain intensity, pain unpleasantness, pain interference, and quality of life 6 months after program enrollment. The effects on pain intensity and unpleasantness were notably large in magnitude. Average motivation to manage pain was initially quite high (8.58/10), and did not significantly change during follow-up. Confidence in managing pain did not change significantly over the course of the study, but remained at a consistently moderate level (approximately 6.5/10). The results also suggest that most participants found the program to be user friendly and of good or better quality. Overall, our results indicate that this tailored, online, chronic pain management program is a promising, low-cost, user-friendly intervention with the advantage of virtually unlimited scalability. However, future randomized controlled studies are necessary to ensure that the promising results of this study were because of the effects of the intervention and not the simple effects of time.Next, we conducted tests to determine what characteristics distinguished the participants whose pain responded favorably to the intervention from those who did not experience improvement in their pain. First, we found that lower pain intensity and unpleasantness were associated with treatment response, which suggests that the intervention may be most helpful for people experiencing mild to moderate pain. Other characteristics predictive of treatment response include better baseline sleep quality, better emotional functioning, more adaptive cognitions, and a goal-oriented cognitive style. These findings suggest that treatment responders have somewhat better psychological health before treatment. This may indicate that the program works best for people with some psychological resilience. Alternatively, these findings may indicate that the program does not address co-occurring problems of mood, anxiety, stress, emotion regulation, or sleep adequately, leading individuals with these problems to benefit less from treatment. Thus, the effectiveness of the online pain management program might be improved by increasing tailoring and content to address these potential shortcomings. Similarly, treatment responders appeared to be physically healthier , use less medications, and use fewer health services. Overall, this pattern suggests that the Web-based chronic pain management intervention may be most effective for those individuals with mild or moderate chronic pain that have better overall psychological and physical health at the time they initiate the program. Individuals with more numerous comorbidities or certain pain conditions  may require a more intensive, disease-specific, face-to-face intervention to achieve optimal outcomes. Alternatively, Web-based pain management interventions could benefit from program development to tailor the program content more deeply to address the needs of these individuals.Ease of access may be especially important for people with chronic pain when pain flares unexpectedly and immediate access to resources that promote adaptive pain coping strategies  can provide relief. Additionally, the convenience of using Internet-based pain management from home can lead to greater access to the program tools, reaching individuals with pain that might not otherwise seek out treatment because of disability, physical limitations, lack of transportation, distance, or time .As a result of the easy access to Internet-based pain information, there is a virtually unlimited amount of online information available to individuals experiencing chronic pain. The downside to this is that the sheer amount of available information can be overwhelming, and the validity of this information is often specious. Tailored, online, evidence-based pain management programs identify the unique needs of individual chronic pain clients, match these needs with key information and evidence-based interventions, and deliver them in manageable amounts ,41,91. TThis study has several noteworthy strengths. First, the participant sample was large and diverse with regard to geographic location, occupation, race/ethnicity, and age. This sample offers greater generalizability of results to typical chronic pain sufferers than results derived from undergraduate psychology student convenience samples that are ubiquitous in the psychology literature. Next, the nature of the online pain management program allows us to conclude that the intervention was implemented with nearly perfect consistency. Third, the naturalistic design and longitudinal follow-up support the external validity and generalizability of the study in comparison with tightly controlled laboratory-based studies. Finally, we reported effect sizes and odds ratios to enable the reader to readily assess the clinical significance/magnitude of change associated with our outcomes, and easily compare these with other pain management study results.This study also has some limitations that should be made explicit. First, because this was an uncontrolled study, we cannot be certain that the findings were not the result of regression to the mean, or effects of time rather than the intervention itself. Thus, these results should be interpreted as promising evidence, but certainly not conclusive. Second, because participants in this study self-selected the online pain management program, we cannot determine if the pattern of effects we observed generalize to others who would not elect to participate in this program. However, given that pain patients nearly always self-select their own pain management methods from available options , this design has ecological validity. Third, limitations in the available data preclude examination of the extent to which participants interacted with the program. Although the program is designed to be self-paced and accessed at-will by the individual, it would have been desirable to test dose–response relationships. Fourth, all the outcomes were based upon brief self-report data and monomethod measurement can be subject to reporting biases . Objective measures of pain disability  and/or collateral reports of pain behavior would have addressed this problem, but were not logistically possible. Longer, more commonly used outcome measures with well-established validity evidence would also have improved the quality of this study. However, participant burden was the impetus for selecting very brief measures in this naturalistic study. Because participants were not compensated for the significant time it takes to complete lengthy measures (as is the norm in laboratory-based research) the pragmatic decision was made to design the programs with the very brief measures of outcome.First and foremost, well-powered randomized controlled trials of tailored Web-based pain management programs are needed to determine time and self-selection effects versus intervention effects on pain and psychosocial outcomes. Future studies should also make use of well-validated measures of pain outcomes  and takeNext, future researchers should also measure change in theoretically relevant proximal variables  to test mechanisms of the effects of tailored Web-based pain management programs. Once efficacy is established, there will be a need for dismantling studies to examine whether there are differential effects of tailoring program content on certain variables  versus others. Finally, empirical evidence showing which variables exert the greatest tailoring effects (vs those with weak or no effects) on outcomes should guide development of future interventions and improvement of those currently in existence.


An 8-year-old boy was referred to our institute with dysmorphic features such as mild lupus, micrognathia, low hair line, hypoplasia, hemi atrophy of left side of the face, abnormal size of ears, hypothenar, hypoplasia of chin, and tongue tie. MRI scan was found to be normal and EEG suggestive of generalized seizure disorder. Cytogenetic evaluation of the proband revealed a pericentric inversion of chromosome 8 with 46, XY, and inv 8  karyotype. Pericentric inversions are among the frequent chromosomal rearrangements associated with genetic disorders with a frequency of 1-2% . In thisAn 8-year-old male child with dysmorphic facies and mild mental retardation was referred to the Institute of Genetics, Hyderabad for cytogenetic evaluation. He was born after full term as the third child in the sibship of nonconsanguineous parents. He had delayed developmental milestones, neck holding at the age of 5 months, walking independently at the age of 2 years and 5 months, and started speech at the age of 3 years and 5 months. The dysmorphic facial features included mild lupeus, micrognathia, low-hair line, hypoplasia, hemiatrophy of left side of the face, abnormal size of ears, hypothenar, hypoplasia of chin, and tongue tie. His external genitalia were normal. Psychological evaluation of the child was carried out using Senguin form board and Vineland Social maturity physical examination scale . The intMRI Scan report of the propositus was normal, but his EEG study was suggestive of generalized seizure disorder. He had hyperactive behavior with slurred speech. It is informed that the boy was frightened by loud sounds and is presently attending a special school.de novo. Chromosomal analysis of peripheral blood lymphocytes was performed using GTG banding for the propositus and their parents , 6. A rede novo are sometimes associated with abnormalities as there is a potential for gene disruption or position effect [Inversion comprises approximately 10% of structural aberrations where pericentric inversions clearly outnumbered paracentric rearrangements. Pericentric inversion results from a two-break event in which there is a break in each arm including the centromere. Reorientation of a sequence of genetic material apparently does not influence its function, and breakage reunions at most sites do not cause an abnormal phenotype. Most pericentric inversions involve breakpoint in the centromeric heterochromatin of chromosome 1, 9, and 16. These inversions are generally inherited and considered clinically insignificant heteromorphisms as their breakpoints are in the repetitive noncoding sequences. In contrast, inversions with euchromatic breakpoint when they occur n effect . Pericentric inversions have been described in every chromosome with varying frequencies. Inversions of chromosome 8 account for approximately 8% of all observed pericentric inversions, which include the rare occurrence of inversions in chromosome 1, 8, and 16. A possible reason for such rare finding may be due to unequal crossing over causing lethality [Pericentric inversion of chromosome 8 has been reported in 50 unrelated families. The break points in the short arm involve band p 11, p 12, or p 2 while break points on the long arm are evenly distributed along all its length . StanleySome of the clinical features observed in the propositus are similar to the earlier reports of partial overlap of the chromosomal imbalance. However, the variable features such as mild mental retardation, facial dysmorphology, and hyperactiveness can be attributed to the inversion fragment between p 11.2 and q 21.2. , 11. TheAnalysis of the p 11.2 and q 21.2 bands at the genetic level showed the presence of genes; CHRNA2 gene-cholinergic receptor, nicotinic, alpha 2 , FGFR1 gene-fibroblast growth factor receptor 1, GDAP1 gene-ganglioside-induced differentiation-associated protein and KCNQ3 gene-potassium voltage-gated channel, KQT-like subfamily, and member 3 which are essential for the normal functioning of the brain. Disruption of these genes due to the chromosome rearrangement may alter the modulation of the neuroproteins which in turn may influence normal functioning of brain resulting in mild mental retardation and seizures as seen in the propositus . The rea


Objective. This study aimed to evaluate epidemiological, clinical, laboratory, and neuroimaging features of 160 adult patients with tuberculous meningitis (TBM) according to “Thwaites' diagnostic index.” Methods. The subjects of this retrospective study are the patients with TBM who were followed up between years 1998 and 2009 in a tertiary referral hospital. Diagnosis of TBM was based on clinical, laboratory, and neuroimaging signs and Thwaites' diagnostic index. Results. Mycobacterium tuberculosis was isolated from CSF in 59 of 148 patients. Seventeen percent of the patients died, 71% recovered completely, and 13% recovered with neurological sequel at the end of the sixth month. Conclusions. Despite new developments in laboratory or neuroimaging techniques, the diagnosis of TBM is still based on clinical features with the help of laboratory. Early diagnosis by suspecting TBM may prevent therapy delay and may result in decrease in the mortality and morbidity. Tuberculosis (TB) is a disease which has been affecting humanity since archaic ages. Although tuberculous meningitis (TBM) is the least commonly observed form of extrapulmonary TB 5–15%), it is the most severe form in terms of mortality and morbidity 5%, it is. It deveOur objectives in this study are (1) to review the clinical, laboratory, and radiological findings from 160 TBM cases diagnosed, treated, and followed up at a single center in the light of the literature, (2) to present the local epidemiological data from our cases, and (3) to highlight the results from our cases and emphasize the significance of the Thwaites' diagnostic index, which we consider a practical and easy-to-implement guide.The cases in the study were patients older than 14 years of age who were diagnosed with TBM at our hospital during the 11-year period between January 1998 and March 2009. Clinical, laboratory, and radiological characteristics of the cases, which were obtained through the retrospective review of hospital files and outpatient follow-up files, were summarized by using a standard data collection table. Cases with incomplete data or uncertain diagnosis were excluded from the study.M. tuberculosis in CSF or in other sterile body fluids or in tissue with PCR, (3) close or familial contact with an active pulmonary TB case, (4) prior TB or family history of TB, (5) characteristic findings suggesting TB in cranial imaging , (6) presence of pulmonary TB findings such as active infiltration, miliary pattern, or cavity in pulmonary imaging, and (7) clinical response to antituberculosis therapy (ATT). In addition, Thwaites' diagnostic index was used retrospectively for cases followed up until 2002, prospectively for cases followed up between 2002 and 2009, and cases with a score value ≤4 were considered TBM [ TBM was diagnosed based on the clinical characteristics, laboratory, cerebrospinal fluid (CSF) findings, and radiological imaging methods. Cases suffering from fever and headache for two weeks or more, with a stiff neck or altered sensorium detected in physical examination, and with lymphocytic pleocytosis, decreased glucose, and increased protein levels detected in CSF examination, were considered lymphocytic meningitis. Lymphocytic meningitis cases with these characteristics were considered TBM in the presence of the following additional criteria: (1) detection of acid-resistant bacteria in CSF, other sterile body fluids, tissue under direct microscopy with EZN staining, or growth of such bacteria in culture, (2) demonstration of the DNA of ered TBM . The casclinical criteria (maximum category score = 6),CSF criteria (maximum category score = 4),cerebral imaging criteria (maximum category score = 6),evidence of tuberculosis elsewhere (maximum category score = 4).M. tuberculosis infection. 59 cases fit this definition. Probable tuberculous meningitis: when imaging is available, a diagnostic score of 12 or above is required (28 cases), and when imaging is not available, a diagnostic score of 10 or above is required (12 cases). Total 40 cases fit this definition. Possible tuberculous meningitis: when imaging is available, a diagnostic score of 6–11 is required (56 cases), and when imaging is not available, a score of 6–9 is required (4 cases). Total 60 cases fit this definition. One case was excluded from the study in which lumbar puncture and imaging are not possible [All cases were classified as definitive, probable, possible, or not tuberculous meningitis, depending on their total diagnostic score. Definite tuberculous meningitis: it is the microbiological identification or evidence from commercial nucleic acid amplification tests of CNS possible .The cases were clinically evaluated and neurologically staged during admission to the hospital based on the British Medical Research Council criteria . AccordiThe cases were treated with the classical four-drug ATT  for 12–18 months. Some cases with prior TB received a five-drug therapy including streptomycin. Cases with antituberculosis resistance received a combination therapy including minor drugs. Advanced stage cases with neurological findings were also given intravenous dexamethasone therapy for eight weeks.The 160 TBM cases included in the study were aged 14–78 with a mean age of 32.18 ± 13.62. Half of the cases were female. At the time of admission to the hospital, only 16% of the cases were stage I, while 84% were stage II and stage III. All cases were tested for HIV/AIDS, and only one male had positive HIV serology. Two cases were pregnant, and one case had given birth four months ago. The demographic, clinical, laboratory, and radiological findings of the cases are summarized in  The symptom duration of the cases varied between two and 365 days. The time between the onset of complaints and application to the hospital was less than one week in 11 cases (7%), 1–3 weeks in 91 cases (57%), and more than three weeks in 58 cases (36%). This duration was longer than six months in two cases and 12 months in one case.  The most frequent symptoms observed at the time of admission were headache (86%), nausea vomiting (64%), and altered sensorium (59%). While the most frequent finding was stiff neck (88%), meningeal irritation was detected only in 37% of the cases. During initial admission, 24% of the cases had cranial nerve palsies, 21% were in precoma/coma state, and 16% had convulsions. Abducens nerve palsy was the most frequently observed cranial nerve palsy, followed by oculomotor and facial nerve palsies. Four cases had oculomotor, and four had acoustic nerve palsies. According to the Thwaites' diagnostic index , all cas38% of the cases had accompanying extraneural TB, primarily pulmonary TB. Extraneural TB cases comprised pulmonary TB in 47 cases, Pott's disease in six cases, renal TB in two cases, and gastrointestinal and skin TB in one case each. In addition, 43 cases (27%) had prior TB, and 31 cases had family history of TB (19%). 37 cases (23%) had underlying diseases including diabetes mellitus (10), trauma (6), pregnancy/delivery (4), alcoholism (4), malignity (3), convulsions (2), idiopathic thrombocytopenic purpura (1), mental retardation (1), SLE (1), multiple sclerosis (1), herpes zoster (1), cerebrovascular disease (1), vitiligo (1), and HIV/AIDS. M. tuberculosis was isolated from CSF in 59 (40%) of the 148 cases who could be subject to lumbar puncture and from other body parts in 7 cases in the Lowenstein-Jensen medium. Blood WBC counts were 1,500–32,800/mm3 and within normal limits in 97 cases (61%) . Erythrocyte sedimentation rate was increased in 75% of the cases (66/87); positive and anergic reactions were observed in 33% and 49% of the 43 cases tested with PPD, respectively. 3(1–2290/mm3), and lymphocyte domination was detected in 65%. CSF/serum glucose ratio was <0.6 and <0.3 in 95% and 55% of the cases, respectively. CSF protein was normal in only 13 cases and >100 mg/dL in 72% of the cases. In CSF examination, mean leukocyte count was found to be 233/mm TB-associated findings were observed in the chest X-rays of 73 of the 101 cases (72%). 25 cases had miliary pattern, 35 had active parenchymal infiltration, seven had cavitary lesions, and six had pleurisy. Of the cases on which cranial imaging could be performed , only contrast CT was used in 32 cases; only contrast MRI was used in 75 cases, and combination of CT and MRI was used in 27 cases. The most frequently identified cranial radiological findings were tuberculoma , basal meningitis , hydrocephalus , and ischemia/infarct  . ATT and dexamethasone therapy were started between the 1st and 33rd days of hospitalization. Therapy was started within the first 3 days in 76% of the cases, within 4–10th days in 18%, and on the 33rd day in one case. 92% of the cases were given the classical four-drug therapy consisting of INH, RIF, PRZ, and EMB, while 6% of the cases received a five-drug therapy including streptomycin. During hospitalization, 56% of the cases recovered completely, 34% recovered with neurological sequelae, and 10% died. During the six-month follow-up period, these rates changed to 71%, 13%, and 17%, respectively. Majority of the dying cases died within the first ten days, and 13 of the 27 cases had an underlying disease . The mean age of the dying cases was 45; 16 of them were stage III and 11 were stage II. Of the dying cases, seven were in coma state at the time of admission to the hospital, two had altered sensorium, and two had a neurological deficit. Two cases died on the day of admission to hospital, two died on the 3rd day before therapy could be started, and in two cases, ATT was started on days 24 and 33 following hospitalization. 10 of the dying 27 cases had leukocytosis. M. tuberculosis was identified by Robert Koch in 1882, TBM was clinically described by Robert Whytt in 1762 for the first time in children with acute hydrocephalus [Before cephalus . Until tcephalus , 12. As TBM is most frequently seen as a complication of the primary infection during the first five years of life in countries with a high incidence of TB, while it basically develops through the reactivation of meningeal or subcortical focus in adults aged 25–45 in countries with a low incidence. In large trials conducted in Turkey, young adults aged 15–30 have been reported as the group with the highest incidence rate , 14. In During hospital admission, 63% of the cases were stage II, and 21% were stage III. At this time, 59% of the cases had altered sensorium, 16% had convulsions, 21% were in a coma state, and 15% had paresis/plegia, all of which were neurologically serious cases as in the study by Sütlaş et al. . HoweverM. tuberculosis has largely been isolated in a maximum of half of the cases reported in Turkey. In our study, TB culture positivity in CSF (40%) was found to be higher than the other reports in our country [TBM is both an insidious disease, and it can have an atypical clinical picture. Identification and monitoring of patients according to standard case definitions are important in providing comparable results among different studies. Therefore, suspecting TBM could save lives in cases with nonspecific symptoms such as long-lasting fever, weight loss, and adynamia in the presence of clinical signs like headache, nausea vomiting, and absent mindedness, which are suggestive of intracranial pressure increase if there is also accompanying pulmonary TB, family history of TB, or close contact with an active TB case. Headache, fever, and nausea vomiting were the most frequently observed complaints in our study. Thwaites' diagnostic index scoring was reported to be a practical, precise, and specific that can be used to differentiate TBM from bacterial meningitis based on age, disease or complaint duration, WBC count, and CSF findings , 22, 23.y in CSF 0% was fo country , 24, 25.The cases in the study were diagnosed based on clinical, laboratory, and radiological findings. Typical CSF findings, family history of TB, close contact with an active TB case, and prior TB in addition to high culture positivity aided the diagnosis. Additionally, the presence of accompanying extraneural TB, primarily pulmonary TB, and characteristic findings of TB in cranial imaging in 38% of the cases once again demonstrates the importance of radiology for TBM diagnosis. Of the 136 cases on which cranial imaging could be performed, combination of CT and MRI was used in 27 cases, and positive findings in MRI were identified in eight of the 13 cases that are found to be normal with CT. The results from our study, where a higher number of basal meningitis, tuberculoma, leptomeningeal palsy and infarct cases could be demonstrated with MRI, are consistent with the publications stressing the superiority of MRI to CT , 27. In BCG is in children vaccination schedule in Turkey. Therefore, PPD positivity is not useful in diagnosis. However, since interferon-gamma release tests, that are more widely in use in recent years, do not have cross-reaction with BCG; they are more helpful in diagnosing latent TB. Consequently, as in every form of TB, TBM is still a major health issue in Turkey. The diversity of its clinical findings and the lack of practical and reliable methods for early diagnosis encourage the clinicians involved with the disease to create diagnostic guidelines to reduce mortality and morbidity and to spread the use of such guidelines , 24. The


Coronary artery bypass graft (CABG) is a treatment strategy to relieve the symptoms of coronary artery disease (CAD). Based on determining the long term outcome of CABG using SF-36 Health Related Quality Of Life (HRQOL) questionnaire, the present study was conducted in our center to determine the CABG results one-year after the operation.Between March 2005 and August 2009, 112 patients with coronary heart disease (CHD) who underwent coronary artery bypass graft (CABG) were enrolled. Patients completed SF-36 HRQOL general health status questionnaire. Stepwise multiple linear regression models were used to detect independent variables predicting changes in each eight subscales of SF-36 questionnaire.The mean age of patients was 61.4±0.9 years and most of them were male with three vessel diseases that were on pump CABG. The mean physical and mental component summary scores were 59.5±0.9 and 60.2±0.9, respectively. Physical functioning (PF) and role physical (RP) improved in males. Regression models showed that there were some statistical models with low R-square to predict role emotional (RE), general health (GH), PF and RP according to ejection fraction after surgery, diabetes, pump type of CABG and male gender.CABG has led to higher and more satisfactory outcomes for PF, RP and RE but lower in other scales comparing with normative data of the society and one-year post-operative scores of other studies. It could mostly be attributed to unmodified risk factors and progression of existing comorbidities. Cardiovascular diseases (CVD) are still one of the leading causes of morbidity and mortality worldwide. In Iran, the most common form of this disease is coronary artery disease (CAD) with a prevalence of 37.5% in women and 22.2% in men based on the Rose questionnaire and Minnesota coding  and accoThe short form, 36 questions (SF-36) general health status survey, is a single 36 item scale recommended by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) used for evaluating HRQOL in patients with cardiovascular disorders as well as normal population and individuals with various disease states that allows calculation of numerical scores for eight dimensions of health.  The SF-3Regarding this lack of research for measuring longer term outcomes with the use of SF-36 in Iran, the present study was conducted to determine if CABG results into satisfactory outcomes one-year after the operation.Between March 2005 and August 2009, 112 patients with coronary heart disease (CHD) who had undergone a coronary artery bypass graft (CABG) were randomly (using EPI software for a simple randomization) selected. Cases were referral of Department of Cardiac Surgery, Baqiyatallah University of Medical Sciences, Tehran, Iran. Considering α=0.05, score of the QOL equal to 70%, precision about 8.5%, and by using estimation of a ratio formula, the sample size was estimated 112 cases.The inclusion criteria were undergoing CABG at least 12 months ago and signing a written informed consent form to complete the SF-36 questionnaire. The Ethical Committee of Baqiyatallah University of Medical Sciences approved the study protocol. Patients completed SF-36 questionnaire themselves (self administered). In case of illiteracy, one trained secretary helped them to fill the questionnaire. In addition, we assessed demographic variables of age, gender, height, weight, duration of hospitalization, date of enrollment, CHD risk factors , number of diseased and grafted vessels, type of surgery (on pump or off pump), duration of aortic cross clamp and CABG, and ejection fraction before and after surgery according to the medical history, physical examination, laboratory tests and patients’ file if necessary. In addition, to determine left ventricular ejection fraction (LVEF), a transthorasic echocardiography was done by the cardiologists. Normal range of lipids is considered as triglyceride (TG) < 150, low density cholesterol (LDL) < 100, and total cholesterol (TC) < 200 mg/dl for both men and women.Quality Metric's SF-36v2® Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view. It is a practical, reliable, and valid measure of physical and mental health that can be completed in five to ten minutes. The SF-36v2 provides scores for each of the eight health domains, and psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores,  Table 1Table 1. We used mean±SE for description of quantitative variables. Pearson and Fisher Exact, Chi-Square, student and paired t tests, one-way analysis of variance, Pearson correlation were used for statistical analysis. We used stepwise multiple linear regression models with Pearson correlation coefficient (r) to detect independent variables that can predict changes in each eight components of SF-36 HRQOL questionnaire. Differences and correlations with p<0.05 were considered statistically significant. We used SPSS 13 software  in the analysis.The mean age of patients was 61.4±0.9 years and most of them were male. Most of them had three vessel diseases and underwent on pump CABG .Ejection fraction (EF) before and after surgery were 44.7±0 .7 and 49±0.6, respectively. Statistical analysis showed that it has increased significantly (p<0.001). The mean physical and mental component summary score of their HRQOL were 59.5±0.9 and 60.2±0.9, respectively. Mean score of eight subscales of HRQOL of patients after one year of CABG was 86.9, 83.3, 74.6, 53.4, 52, 48.3, 47, and 33 for RE, RP, PF, VT, MH, SF, GH, and BP, respectively .The male to female ratio was 2.6 to one. PF  and RP  were better in males. Mean physical component summary score was significantly higher in males  but mean mental component summary score had no difference in both genders. Type of surgery had a significant effect on general health. Patients on pump surgery had a better general health status than off pump subjects .Patients with DM had higher score of emotional role in comparison with cases without DM . EF after CABG was negatively correlated with emotional role . Physical functioning was also negatively correlated with EF before  and EF after  CABG. The regression models  showed tIn this study, one year post CABG, SF36 results showed that subscales of BP, GH, VT, SF and MH were lower than Iranian’s normative data; but, subscales of SF, RP and RE were higher. Additionally, in comparison with other similar studies, RP and RE scales were higher and other subscales were mostly lower . FurtherComparison of our results with one-year post CABG findings of four different studies conducted in UK, Australia, USA and Poland separately,12]13][[13][12][[[13][12]Other reasons for the differences between our study and others can be due to the fact that, the HRQOL would not improve in a linear way for all patients following CABG. It is also due to higher rates of comorbidities and three vessel patients in our study. As there were no pre-operative baseline data for SF-36, the results of this study were compared with Iranian’s normative data which was published by Montazeri et al.,  in 2005.About the PF scale, although it was higher in our study, the difference was not significant and its range was almost the same in the two studies. Finally for other scales, our results were lower than norms and the difference was more significant in BP scale. Comparison of these one-year postoperative scores with Iranian healthy individual’s normative data indicated that our patients had lower measures in most health domains except in PF, RP and RE.Subjects in our study had a worse mental health condition compared with their physical health and the mental health reported in other studies. One possible explanation of these differences is perhaps the continuation of existing comorbidities in our population which could negatively influence the subjective and multifactorial nature of the concept of HRQOL. It means that the patients probably have not properly modified their risk factors after the operation. Other reasons could be the poor participation in cardiac rehabilitation programs which have proved to have a great effect on quality of life after the operation  or noncoIn our study, men had higher scores in the subscales of PF and RE. With difference in significant scales, results of this study are in line with other surveys regarding higher scores in men.20] It c It c20] In our study, the patients with diabetes mellitus had higher RE in comparison with non diabetic patients while according to another study,  the diabThe authors of this study recommend a regular and strict follow up for participation of patients in cardiac rehabilitation programs which have been proved to have a great effect on quality of life of patients after the surgery,  the poinOne of the limitations of this study was that no pre-operative baseline SF-36 data was available. Therefore, a comparison of pre-operative and post-operative data was not possible, so it was difficult to draw conclusions for post CABG while no baseline were available.The other problem was the weakness of the SF-36 which could not control the effects of comorbidities which may have resulted in various studies. HRQOL of the patients after one year from CABG was relatively good. In this survey, CABG has led to higher and more satisfactory outcomes for PF, RP and RE but lower in other scales comparing with normative data of the society and one-year post-operative scores of other studies. It could mostly be attributed to unmodified risk factors and progression of existing comorbidities.


Trypanosoma brucei gambiense trypanosomiasis, who had been treated with melarsoprol in some disease-endemic areas, subsequently relapsed. To determine whether the frequency of postmelarsoprol relapses increased over time, we reviewed data from 2,221 trypanosomiasis patients treated with melarsoprol during this period in Nioki, Democratic Republic of Congo, from 1982 to 2001. The frequency of relapses was 5.6%(31/553), 6.8%(35/512), 4.5%(18/398), 11.4%(34/299), and 5.0%(17/343) for those treated from 1982 to 1985, 1986 to 1989, 1990 to 1993, 1994 to 1997, and 1998 to 2001, respectively. The higher frequency of relapses in 1994 to 1997 was associated with an incremental dosage regimen of melarsoprol. In multivariate analysis, after adjustment for treatment regimen, sex, residence, and trypanosomes in cerebrospinal fluid, postmelarsoprol relapses did not increase in Nioki, perhaps because 1) little drug pressure exists; 2) subtherapeutic doses have rarely been administered; 3) little potential exists for the preferential transmission of melarsoprol-resistant strains.Recently, a high proportion of patients with late-stage  Trypanosoma brucei gambiese trypanosomiasis may be increasing, at least in 3 foci where the frequency of postmelarsoprol relapses is higher than the 5%–8% generally seen elsewhere , is located in the Bandundu Province of DRC, at the confluence of the Mfimi and Molibampe Rivers. Several trypanosomiasis foci are located on the Mfimi River (inhabited by the Basakata) while others lie on the Molibampe River (populated by the Bampe) or on the road going north from Nioki (populated by the Baboma and the Basengele). These 3 areas, as well as Nioki town , represent natural subdivisions of the Nioki District. Patients from Nioki town can acquire their infection either in Nioki itself, where there are infective tsetse flies, or when traveling in rural parts of the district.T.b. gambiense trypanosomiasis treated in Nioki hospital from January 1, 1982, to December 31, 2001, were included in this observational study; follow-up data were accumulated until December 31, 2003. Most cases were diagnosed at Nioki hospital, while a minority were referred by case-finding mobile teams or rural health centers. Case-finding teams were active in the 1980s, collapsed around 1991  CSF leukocyte count of 20 to 49/mm3, higher than the previous determination, with the presence of symptoms compatible with a relapse. When in doubt, the lumbar puncture was repeated 1–2 months later. In practice, distinguishing a genuine relapse from a reinfection is not possible, and we will use "relapse" to designate both. The primary analysis of risk of relapsing considered all relapses, regardless of the interval since melarsoprol treatment; in a secondary analysis, only relapses happening within 2 years of treatment were considered.After treatment, patients were followed up with lumbar punctures every 6 months for 2 years. Most of the follow-up lumbar punctures were performed at Nioki hospital; in the earlier years, some of these were performed by mobile teams during visits to disease-endemic villages. The patients were asked to come back sooner if they experienced symptoms compatible with a relapse . The decision to administer a second treatment (and thus to consider this case as a relapse) was left to the discretion of the attending physician, but most fulfilled one of the following criteria: 1) trypanosomes found in the CSF (or rarely in the blood or lymph node aspirate); 2) CSF leukocyte count ≥50/mmFor each case, we collected data on age, sex, village of residence, date of diagnosis, mode of diagnosis , pretreatment CSF leukocyte count, treatment given, encephalopathy or death during treatment, and whether a diagnosis of relapse was made during posttreatment follow-up. Few data were missing with the exception of the village of residence (missing for 61 of 164 patients in 1982) and the precise age (unknown for 1 child and 152 adults). The database did not include information on each follow-up lumbar puncture, but only on those which led to a diagnosis of relapse. Thus, to estimate the frequency of relapses, we used as the denominators all patients who survived treatment.2 test. CSF leukocyte counts that had a non-normal distribution were compared with rank sum tests. Multivariate analysis was performed by logistic regression; variables that enhanced the fit of the model at the 0.05 level by using the likelihood ratio test were retained.Data were entered and verified on EpiInfo 6.04, and analyzed with Stata 8.0 . Proportions were compared with the χ3, a shift occurred over time towards more advanced disease upon diagnosis in recent years, as evidenced by the decrease in the proportion with a positive lymph node aspirate, an increase in the proportion with CSF trypanosomes, and a doubling of the median CSF leukocyte count. Treatment regimens varied considerably over time. The proportion of patients given prednisolone also increased after the randomized controlled trial was conducted (10), and its results generalized; the proportion of patients in whom a melarsoprol-induced encephalopathy developed decreased to 2% in the last 4-year period. The proportion of patients found to relapse, whether all relapses were considered or only those occurring within 2 years of diagnosis, increased significantly during 1994–1997, but decreased to its previous level from 1998 to 2001.The risk factors for postmelarsoprol relapses during this 20-year period are shown in T. b. gambiense trypanosomiasis increased in 1994 to 1997 but returned to its normal level in 1998 to 2001. This was driven essentially by a high risk for relapse among patients participating in a randomized trial who were treated with a regimen of incremental dosage of melarsoprol  than for 2 isolates from Côte d'Ivoire (0.001–0.018 μg/mL); the higher MIC of 0.072 μg/mL was superior to levels that can be expected in CSF (T.b. gambiense isolates from northwestern Uganda were also higher than in isolates from Côte d'Ivoire (As in Uganda and Angola ,19, we fd in CSF . Fifty pd'Ivoire . In suchd'Ivoire ,23. Withd'Ivoire ; we specFinally, our results suggest that variations in the regimens of melarsoprol used in each country may also explain some, but not all, of the high rates of postmelarsoprol failures in specific locations. A regimen of incremental dosage was indeed used in Uganda  and in sT.b. gambiense trypanosomiasis would be monitored in a small number of sentinel centers. The World Health Organization is developing such a system (These findings, although reassuring, underline the necessity of a strengthened surveillance system for African trypanosomiasis, through which secular trends in the frequency of treatment failures among patients with a system . Its mea


Streptococcus pneumoniae serotype 3, isolated from a penicillin-allergic patient and initially susceptible to fluoroquinolones, macrolides, lincosamides, quinupristin-dalfopristin, and telithromycin, became resistant to all these drugs during treatment. Mutations in the parC and gyrA and in the 23S rRNA and the ribosomal protein L22 genes were detected in the resistant isolates. Streptococcus pneumoniae infections and in penicillin-allergic patients with pneumococcal pneumonia. Until now, clinical failures of fluoroquinolones during treatment of pneumococcal infections have rarely been reported . MICs of the antibiotics and criteria of susceptibility and resistance, otherwise not indicated, were those of the broth microdilution procedure described by the National Committee for Clinical Laboratory Standards (NCCLS)  genes and point mutations at Ser-79 in the parC and at Ser-81 in the gyrA genes were detected as previously described  of the isolates were performed according to previously described protocols (S. pneumoniae strain was isolated from sputum obtained before antibiotic treatment with intravenous levofloxacin (500 mg once a day for 13 days) was begun. On day 4, intravenous clarithromycin (500 mg twice a day) was added but withdrawn after 4 doses. On day 14, clinical and radiologic conditions had deteriorated, and treatment was changed to intravenous clarithromycin (500 mg) and intravenous ciprofloxacin (200 mg) twice a day for 7 days. On the same day, a second pneumococcal isolate resistant to levofloxacin and clarithromycin but susceptible to clindamycin was obtained  results.In January 2002, a 71-year-old man, who was allergic to penicillin and had a history of chronic obstructive pulmonary disease, was hospitalized due to pneumonia. The first obtained . The MICS. pneumoniae isolates were susceptible to penicillin (MIC <0.03 μg/mL), trimethoprim-sulfamethoxazole (MIC <0.5/9.5 μg/mL), tetracycline (MIC <2 μg/mL), chloramphenicol (MIC <2 μg/mL), and vancomycin (MIC=0.5 μg/mL). The first isolate was susceptible to both macrolides and fluoroquinolones. This isolate had a levofloxacin MIC of 2 μg/mL, confirmed by all susceptibility methods used , although it had a point mutation in the gyrA gene, as shown in All Escherichia coli numbering) mutation in the sequence of the gene corresponding to the domain V of the 23S rRNA as well as the 6–amino acid insert in the ribosomal protein L22. The four alleles encoding the 23S rRNA gene had the A2058G mutation. The sequences of the fifth isolate, resistant to macrolide antibiotics and clindamycin, with an intermediate susceptibility to quinupristin-dalfopristin, indicated a mutation at position 2058 of domain V, but no insert was found in the ribosomal protein L22.For the second isolate, MICs of macrolides, quinupristin-dalfopristin, and telithromycin were higher than those for the first isolate, and a 18-base insert in the sequence of the gene encoding the ribosomal protein L22 was detected. The result, deduced from the corresponding ribosomal protein, was a six–amino acid (RTAHIT) insertion between amino acids T108 and V109 (GenBank accession no. AY140892). The third and fourth isolates, with resistance to macrolides, clindamycin, quinupristin-dalfopristin, and the highest telithromycin MICs of all the isolates, had an A2058G  led to high level of resistance to telithromycin and increased the quinupristin-dalfopristin MIC (third and fourth isolates).Surveillance studies suggest that the levels of resistance to macrolide antibiotics in gyrA gene, it had no phenotypic expression. In mutants obtained in vitro, other authors observed point mutation in the gyrA gene without mutation in the parC gene with or without phenotypic expression of quinolone resistance  evoke concern.The therapeutic failure and selection of resistance to several antibiotics by