To compare the clinical efficacy of lidocaine 2% with tetracaine 0.5% for cataract surgery.In a randomized, multi-surgeon, controlled clinical trial,122 consecutive cataract cases eligible for topical anesthesia, were randomly assigned to receive lidocaine 2% gel (1 ml) or tetracaine solution 0.5%  before clear corneal phacoemulsification. Main outcome measure was visual analog scale (0 to 10), which was used to measure intra-operative pain. Secondary outcome measures included patients' discomfort due to tissue manipulation and surgeon graded patients' cooperation. Duration of surgery and intra-operative complications were also recorded.P < 0.001). Mean patient cooperation was also marginally better in the TV group (8.3 ± 0.3) compared to LG group (8.4 ± 0.6) (P = 0.25). 96% of patients in TV group showed intra-operative corneal clarity compared to 91% in LG group. TV group had less  intra-operative complications than LG group . No anesthesia related complications were noted in either groupThe mean age in TetraVisc (TV) group was 70.4 years and in the lidocaine gel group (LG) it was 70.6 years (p = 0.89). Patient reported mean intra-operative pain scores by visual analog scale were 0.70 ± 0.31 in TV group and 1.8 ± 0.4 in LG group (Topical TetraVisc solution was superior to lidocaine 2% gel for pain control in patients undergoing clear corneal phacoemulsification. Lidocaine 2% gel is similar to TetraVisc in patient comfort and surgeon satisfaction.Clinical trials number: ISRCTN78374774 Cataract surgery is the most frequently performed surgical procedure in USA. Common forms of local anesthesia for cataract surgery include injection techniques  and topical anesthesia -7. TopicTetraVisc hydrochloride 0.5%, a new viscous topical agent induces rapid anesthesia as it disperses across the cornea rapidly and immediately and offers an extended period of anesthetization due to prolonged contact time .Using a 10-point visual analog pain scale, we evaluated the efficacy of TetraVisc 0.5% solution (TV) and lidocaine gel 2% (LG) in a randomized study in patients undergoing phacoemulsification with intraocular lens implantation.The study was approved by Institutional Review Board/Ethics Committee of University of Florida. 122 patients scheduled for elective cataract surgery and eligible for topical anesthesia were included in the study. Exclusion criteria were unwillingness to have topical anesthesia, high anxiety, dementia or mental instability, deafness, movement disorders, hyperanxiety, and inability to complete the visual analog scale (VAS) of pain line  and any reported allergy to lidocaine or tetracaine. All patients were recruited between January 2006 and November 2006.The patients were randomized by block randomization (randomly assigned by computer generated numbers) to receive either TetraVisc  solution or lidocaine gel  consecutively. Five doses of TV or LG were applied every 5 minutes, 20 minutes prior to surgery. No intravenous or oral sedation was used as pre-medication.Ofloxacin was administered by the patient for 3 days preoperatively in the eye to be operated. Mydriasis was obtained preoperatively with phenylephrine hydrochloride, 2.5%  and tropicamide, 1%  eye drops. In the operating room, baseline pulse and peripheral blood pressure were taken. The lid and periorbital skin were cleaned and the conjunctival cul-de-sac was irrigated with povidone iodide solution. The eye was then draped, and an open-wire speculum was placed. Before the surgeon sat at the operating microscope and began the procedure, the eye was irrigated with balanced salt solution to eliminate lidocaine gel or other anesthetic remnants. The surgical procedure was carried out as a clear corneal phacoemulsification using a superior incision by the phaco chop technique. Balanced salt solution was used for automated irrigation-aspiration. Foldable intraocular lenses (IOL) were implanted. During the surgery, the surgeon was in constant communication with the patients and frequently asked them if they wished to have additional anesthesia. If breakthrough pain occurred in either group during surgery, supplemental topical anesthesia was administered.After the completion of surgery, the patients were accompanied to the recovery room and were asked to grade intra-operative pain using a 0 to 10 visual analog scale (VAS) within 10 minutes of completion of surgery. The patient and independent observer were masked to the anesthesia used.An independent observer also collected surgeons' responses to complete a ten point satisfaction scale immediately after each surgery rating the overall surgical experience. The surgeons were requested to consider not only a subjective impression of patient comfort and ease of surgery but also the presence of inadvertent eye movements, patient reported painful sensations (including pain during the administration of the anesthetic), lid squeezing, and intra-operative complications when providing an overall score. The final score was a general estimate considering all these variables. The scale used rated the surgical experience as 0–10 where 0 is poor cooperation and 10 is excellent cooperation. The need for supplemental anesthesia was recorded. Further information recorded included: patient demographics, operative technique, quantity and type of sedative administered, and volume of anesthetic used for supplemental anesthesia. The power of this study was 92% using a sample size of 61 patients to find a difference in VAS score of 1.0 with a standard deviation (SD) of 0.5 and a type 1 error of 0.05 between groups. For the surgeon satisfaction scale the power was 82% to find a difference between groups of 0.5 with SD of 0.65 and a sample size of 61 patients and a 0.05 type 1 error.Intraoperative complications and corneal clarity were recorded at the end of surgery. Postoperative pain was graded again using a 10-point visual analog scale on the first postoperative day approximately 24 hours later. Student T-test was used to compare both groups. The results of the study are summarized in Table P < 0.001).Intraoperative pain scores by VAS were 0.7 ± 0.31 (mean + SD) in the TV group and 1.8 ± 0.4 (mean + SD) in the LG group. This difference was statistically significant  in TV group and 8.4 ± 0.6 (mean ± SD) in the LG group (p = 0.25).Intraoperative corneal clarity was good in 59 of 61 patients (97%) in the TV group and in 55 of 61 patients (90%) in the LG group (p = 0.16).The mean duration of surgery was 13.1 ± 2.7 minutes overall with mean of 13.4 ± 2.3, 12.4 ± 3.4 and 13.7 ± 2.1 minutes for the 3 surgeons who were involved in the study (p = 0.07). Mean VAS scores for the 3 surgeons were 8.20 ± 0.5, 8.1 ± 0.4 and 8.3 ± 0.4 respectively (p = 0.12).1 out of 61 patients (1.6%) had difficulty in IOL implantation  in TV group compared to 3 out of 61 (4.8%) patients in LG group. All other minor complications  were managed uneventfully during surgery.TetraVisc 0.5% is a recently introduced viscous topical anesthetic used for ocular surgery. It disperses across the cornea rapidly and offers an extended period of anesthesia making it superior to topical gels. Previous reported studies have shown topical tetracaine solution 0.5% with intracameral lidocaine to be safe and effective in cataract surgery .In our study, mean intra-operative pain as measured by visual analog score was less in the TV group than LG group, indicating that topical TetraVisc was superior to lidocaine 2% gel for pain control in patients undergoing clear corneal phacoemulsification. Amiel et al have compared the anesthetic effect of the two drugs and concluded that their effects were similar . But theP < 0.001). No difference was observed between the two groups in terms of surgeons' satisfaction and patient cooperation.Specific factors evaluated during this study included patient comfort and the surgeon's subjective impression of patient comfort and ease of surgery. Visual analog scale is a simple and frequently used method for assessment of intensity of pain . In clinStudies have not shown any corneal endothelial toxicity with lidocaine 2% gel both in animal and humans . In our One of the limitations of the study was non-masked design, and patients were operated by three different surgeons. Inter-surgeon variability in technique and duration of surgery can influence the outcome of the study, even though this has not been the case in our report.In summary, both topical TetraVisc 0.5% and lidocaine 2% gel used independently provide good surgical anesthesia and patient comfort during ocular surgery. The subjective assessment of pain by patients on an analog scale in either group was minimal. No significant intra-operative complications were noted in either group. TetraVisc is superior to lidocaine 2% gel as topical anesthetic for patient comfort while preserving corneal clarity during surgery.LG: Lidocaine gel; TV: Tetravisc; IOL: Intraocular lens.The authors declare that they have no competing interests.KVC and SG were involved in the conception and design of the study; SKG was involved in the acquisition of data; SA and RK were involved in the analysis of the data and preparation of the manuscript.The pre-publication history for this paper can be accessed here:


To the Editor: Neurological manifestations of polycythemia occur frequently (50%-78%) and include headache, vertigo, stroke, visual symptoms, tinnitus, and paresthesia.3/mL and the red cell count was 7.05×106/mm3. The platelet count was normal. The red cell mass was increased to 38 mL/kg  using the principal of isotope dilution by administering 51 Crilabeled autologous red blood cells to the patient and sampling blood over a 2-hour period. Serum erythropoietin levels were mildly elevated. His arterial blood gas assessment showed a pH of 7.37, a PCO2 of 42.9 mm Hg, a PO2 of 62.6 mm Hg, an O2 saturation of 86.6%, and an HCO3 of 22.7 mm Hg. Red cell indices were a mean corpuscular volume of 93.3 fL, a mean corpuscular hemoglobin of 27.2 pg/cell, a mean corpuscular hemoglobin concentration of 30.1 g/dL. The erythrocyte sedimentation rate was 0 mm/h. The peripheral blood smear revealed no abnormal cell or acanthocytes. Renal, hepatic and other metabolic profiles were normal. The chest x-ray and echocardiogram were normal. Ultrasonography abdomen revealed no renal mass or organomegaly. The CT scan of brain was normal. Nerve conduction studies also were normal. The patient was diagnosed as having polycythemia chorea and was managed with phlebotomy (about 250 mL each) and a small dose of haloperidol. Improvement in the clinical picture was simultaneous with normalization of hemoglobin and packed cell volume. The erythrocyte sedimentation rate was 0 mm/h.2/glucose metabolism.2/glucose metabolism. The state of dopaminergic hyperactivity is presumably enhanced by relatively increased neostriatal catecholestrogens. The hypothesis of polycythaemic excess of dopamine-laden platelets releasing excess of dopamine in the neostriatum needs to be confirmed by laboratory evidence of platelet counts. It has been inferred from viscometric studies that red blood cell deformability might be reduced in iron deficiency,7Polycythemia occurs predomnantly in males (3:2) but chorea secondary to polycythemia occurs predominantly in females. The prevalence is 1% to 2.5% of polycythemia patients.In the treatment of chorea with polycythemia, venesection appears to be the initial method of choice. The observation that improvement in chorea may be independent of the erythrocyte count and hemoglobin level suggests that in some cases thrombocytosis is an important factor and that, in these cases, 32P or other bone marrow suppressing agents should also be given.8


The tumor transfer time is 0.7 months and the growth rate is 7.0 cm. per month. The calculated values for times in different phases of the cell cycle for H-35tc2, assuming a log normal distribution for phase duration, were as follows: Tg1 (Gap I)—11.0 hours; Ts (DNA synthetic period)—6.6 hours; Tg2 (Gap II)—4.2 hours; Tm (mitotic time)—0.4 hours. Therefore, the total time, Tc, for one cell cycle was calculated to be 22.2 hours. The potential doubling time was calculated to be 43 hours. The GF (growth fraction) was estimated to be 53 per cent which would suggest that approximately one-half the total cell population is nonproliferating.The 1 hour thymidine labeling indices have been determined for 8 hepatomas which have growth rates which vary by a factor of 14. The indices for these tumors vary only by a factor of 4. Little correlation was found. Preliminary results have been obtained on the kinetics of cell proliferation of the rapidly growing Hepatoma H-35tc


The aim of this study was to compare the renal injury and the quality of images of aortogram using iodinated contrast versus CO2 using digital subtraction angiography (DSA). This prospective randomized study was done in 29 healthy dogs using DSA aortogram. Dogs were randomly assigned to receive iodinated contrast or CO2. 6-F pigtail catheter was introduced via femoral artery approach to perform aortogram under general anesthesia. Serum creatinine (S.Cr.) and urinary enzymes, namely: N-acetyl D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and gamma glutamyl transferase (GGT), were measured before and 48 hours after aortogram. There was no change in S.Cr. in both the groups. Significantly more enzymuria was seen following iodinated contrast than CO2. Enzymuria pre and postaortogram following the iodinated contrast was GGT: 14.9 ± 5.92 vs. 26.2 ± 15.1 (P = 0.001), NAG: 1.63 ± 0.90 vs. 3.6 ± 2.14 (P = 0.0001), and AAP: 1.51 ± 0.75 vs. 3.38 2.41 (P = 0.001), and in the CO2 group was GGT: 15.5 ± 4.9 vs. 21.1 ± 9.04 (P = 0.02), NAG: 2.12 ± 1.06 vs. 3.82 3.27 (P = 0.08), and AAP: 1.28 ± 0.76 vs. 2.51 ± 1.72 (P = 0.03). More than 50% increase over the preprocedural value was significantly less following CO2. Images obtained with iodinated contrast were superior to those with CO2, however, the quality of image with CO2 was adequate for delineation of the renal artery and major branches. Both iodinated contrast and CO2 cause significant enzymuria. More severe enzymuria (>50% increase) was seen significantly less with the use of CO2. Quality of images is better with iodinated contrast.Contrast-induced nephropathy is well-known sequelae of iodinated contrast (diatrizoate meglumine). Carbon dioxide (CO Comparisons of the parameters during baseline and at the end of 48 hours were done using paired 2. The levels of the urinary enzymes were determined by following the method previously reported by us.[et al,[Safety of the procedure was assessed by the arterial blood gas analysis (Roche omni-C) to check for the accumulation of pCOed by us. Ten mills.[et al, whereas s.[et al, and Jungs.[et al, respecti2 and 17 iodinated contrast (diatrizoate meglumine) according to the computer generated randomization. There was no difference in the baseline S.Cr. between the contrast and CO2 [2 from baseline 48 hours after the aortography. There was increase in the PaCO2 after CO2 aortography compared to the preaortography level, but it was not statistically significant (P = 0.06). The baseline tubular enzymes, namely: GGT (P = 0.39), NAG (P = 0.09), and AAP (P = 0.21), were similar between the contrast and CO2. There was significant increase in the enzymuria 48 hours after the aortogram both in the iodinated contrast , and the CO2  as shown in 2, GGT: P = 0.002; NAG: P = 0.0001; and AAP: P = 0.0001.Out of 29 dogs that underwent angiography, 12 received CO and CO2 . There w2 images are negative images, arterial tree seen as white. Images obtained with iodinated contrast agents [2 [2. Although the quality of image with CO2 is not as good as that of iodinated contrast, it still gives adequate delineation of the major vascular anatomy.Images obtained with iodinated contrast are positive images, arterial tree is seen as black, and COt agents  were supgents [2 . Main, d2 as an alternative angiographic contrast agent used in combination with DSA. They showed minimal renal toxicity following CO2 due to a ‘vapor lock’ phenomenon.[2. Even though there was no change in the S.Cr, there was significant increase in the tubular enzymes after iodinated contrast and also CO2. The degree of increase in the enzymuria was significantly more with the iodinated contrast. This shows that even with CO2 there is tubular injury in normal healthy subjects, but significantly less than iodinated contrast.Hawkins and coworkers explored the use of COenomenon. Our stud2 instead of conventional iodinated contrast media. Rapid clearance of CO2 in lungs prevents recirculation and the renal metabolism is likely to be minimally affected.[2 is that, there is no risk of allergic reactions.[2 is the lower contrast properties that the gas provides compared with iodinated contrast agents. Another undesirable effect is that some patients experience nausea after CO2 injection.[There are several advantages of the use of COaffected. Iodinateaffected. Another eactions.16 Howevenjection.2 angiographies does not affect renal function.[It has been reported in several studies that COfunction.7 These s2 is lower than after injection of iodinated contrast medium alone. CO2 alone was not sufficient to visualize the small and narrow vessel. PTRA and stent placement could be performed safely with the addition of small dose of iodinated contrast to the CO2 without significant deterioration in renal function. Drawback of this study was that it was not possible to totally exclude the use of iodinated contrast medium. Hawkins et al, showed that there was a mean decrease in renal blood flow of 11.86% immediately after the CO2 injection which returned to baseline after 24 hours in canine model.[2 toxicity, but the intensity is much less than iodinated contrast. The incidence of CIN depends on the renal function,[et al, showed that, in patients without diabetes, whose S.Cr. concentrations were higher than 1.5 mg per deciliter, the incidence of nephropathy was reduced from 27.0 to 12.2% by the use of low-osmolar agent (iohexol) as compared to high-osmolar agent (diatrizoate). Experimental studies in dogs, in which the use of iso-osmolar contrast medium showed no advantage,[In a recent study, Liss and coworkers found thfunction, diabetesfunction, osmolalifunction, of the cdvantage, but in hdvantage,2 accumulation. The drawbacks of this study are: one, the study was done in canine model and not in humans. Two, we did not study the effect of CO2 with different dosages or multiple boluses. Three, all the dogs were having normal renal functions. Hence, it is difficult to quantify the renal injury with reduced GFR.This study has the following strengths. One, prospective randomized study in canine model, showing the nephrotoxicity and quality of the image. Two, this study measured not only S.Cr. but also the tubular enzymes which are one of the sensitive markers of tubular injury. Arterial blood gas was done to show no significant COIn vitro conditions were created in which bubbles adhered to the tubing of the circuit, creating functional stenosis, or coalesced into larger bubbles that became trapped, thereby reducing flow and augmenting potential embologenic effects of subsequent injections. In canine models the CO2 injections showed potential for ischemic damage owing to vapor lock or transient obstruction to the blood flow in the vessels. The initial lack of blood in the renal cortex after CO2 injection can also explain the decrease in GFR. It is highly likely that the filtration of plasma over the glomerular membrane was momentarily stopped when the gas substituted all the blood.The exact mechanism that accounts for the increased risk of CIN has not been determined, but it has been suggested that medullary hypoxia is a crucial factor for the onset of CIN2. In vitr2 cause significant increase in enzymuria. More severe renal injury measured by changes in the tubular enzymes is seen with the iodinated contrast than CO2. Quality of images is better with iodinated contrast than CO2, but CO2 is able to delineate the aorta and main renal artery.Both iodinated contrast and CO


Sir,Dysrhythmias are well known and not of uncommon occurrence in neurosurgical procedures. The prox2 and N2O (1:2). At the time of tumour resection, there occurred sudden bradycardia and hypotension. There was decrease in heart rate from 70 beats per minute (bpm) to 52 bpm and blood pressure dropped from 110/76 to 68/45 mmHg. The surgeon was immediately informed. No sooner the surgical stimulus stopped, the heart rate and blood pressure reached the pre-stimulus values. Surgery was allowed to continue. To achieve complete haemostasis, the surgeon irrigated the surgical wound with 10 ml of diluted 3% hydrogen peroxide solution (1:1). The effervescent solution resulted in a sudden decrease in heart rate from 76 bpm to 45 bpm. The solution was immediately aspirated and field irrigated with normal saline. The heart rate gradually improved over next 15 seconds. No further use of hydrogen peroxide was allowed. Rest of the surgical and anaesthetic course was uneventful. At the end of 5 hour surgery, anaesthetics were discontinued, neuromuscular block reversed with neostigmine and glycopyrrolate and tracheal extubation done.A 16-year-old female was admitted to our neurosurgical unit with presenting complaint of acromegalic features. Magnetic resonance image (MRI) of the head revealed a 5.2 × 3.2 × 4.5 cm lesion in the sellar extending to suprasellar region, suggestive of pituitary tumour. The patient was scheduled for elective craniotomy and tumour resection. The patient was premedicated with intramuscular glycopyrrolate 0.2 mg, one hour prior to surgery. General anaesthesia was induced with fentanyl 2 mcg/kg and thiopentone 4-5 mg/kg. Tracheal intubation was facilitated with rocuronium 1 mg/kg. An arterial line was placed in the dorsalis pedis artery of left foot. Anaesthesia was maintained with isoflurane (MAC~ 1 ± 0.2) in a mixture of OTCR is a well recognised phenomenon that classically comprises bradycardia, arterial hypotension, apnea and gastric hypomotility. TCR is aWe suggest that the possibility of TCR should be kept in mind during surgery for pituitary tumours.


Oesophageal cancer is the eighth most common cancer in the world, with striking geographical variations in incidence . It accoWe analysed data for 65 591 patients diagnosed with oesophageal cancer in England and Wales during the period 1986–1999, approximately 84% of those eligible, with follow-up to the end of 2001. Exclusions from analysis were mainly of patients whose recorded survival was zero (10.8%) or whose cancer of the oesophagus was not their first primary malignancy (3.6%). A third (34%) of tumours were squamous carcinomas, but the proportion classified as adenocarcinoma rose from 32 to 44% during the 1990s, continuing a steady increase from 15% in the early 1970s .Relative survival at 1 year increased significantly from the late 1980s to the late 1990s in both sexes, from 23.8 to 29.6% in men  and from 24.4 to 26.8% in women (+1.4% every 5 years) . Five-yeThe deprivation gap was more marked in men . For 1-ySurvival from oesophageal cancer in England and Wales remains very poor, with 5-year relative survival approximately 7.5%, and no major improvement for patients diagnosed between 1986 and 1999. Five-year survival was already 6–7% for patients diagnosed in 1971–1975 (


Binary mixer of one hydrophilic polymer (hydroxypropylmethylcellulose) and one directly compressible Eudragit (RS PO) was used in tablets prepared by direct compression. The amounts of both polymers were taken as independent variables for the 32 Factorial design. The percent drug releases at 1, 6, 12 and 20 h were selected as responses. The main effect and interaction terms were quantitatively evaluated using mathematical model. Dissolution data were fitted to zero order, first order, and Higuchi's release kinetics to evaluate kinetic data. Both the diffusion and erosion mechanisms were responsible for drug release as shown by the power law. The release of Alfuzosin was prolonged for 20 h by binary mixer indicating the usefulness of the formulations for once daily dosage forms.The aim of the present study was the determination of formulation factors and the  Alfuzosin hydrochloride, a selective alpha adrenergic antagonist is used against benign prostatic hypertrophy (BPH)–3 in eldet al., where n is the number of dissolution sample times, and Rt and Tt are the individual percentages dissolved at each time point t for the reference and test dissolution profiles respectively[A higher value of MDT indicates a higher drug retaining ability of the polymer and vice-versa. Similarity factor  software at 5% significance level.in vitro dissolution.Stability study of selected formulations was tested according to International Conference of Harmonization guideline. The tablets were stored in Alu-Alu blister for 3 mo in stability chamber  at 40°/75% RH. After 3 mo, tablets were tested for drug content and 2 (1.14±0.18 kg/cm2) as shown in The weight variation of the tablets ranged between 0.13-3.0% (1.25±0.39%), thickness between 4.2-4.5 mm (4.35±0.03 mm) and hardness was within 0.5-2.15 kg/cmst h  of in vitro dissolution. It took 4-5 h to release about 50% of drug  and 75% drug released within 10 h  from all formulations . The data indicates up to 40% Eudragit is not sufficient for reducing release of freely soluble drug like alfuzosin. On the other hand, when the Eudragit quantity was kept constant and HPMC level was increased, the drug release continued to fall. For instance, in Methocel-Eudragit w/w 90/60, 120/60 and 150/60 ratios the mean drug release after 12 h was 92.62, 81.59, and 76.12%, respectively.About 25% of drug was released within 1ulations , fig. 1.2=0.97-0.99) and Korsmeyer (r2=0.98-0.99) kinetic models (All the tablets showed good fit for Higuchi (rc models . From Hi2<50). Tablets containing DCP released slightly more drug than MCC containing formulation (2>50).The tablets in the experiment were primarily prepared with microcrystalline cellulose (MCC) as filler. The effect of other fillers, such as directly compressible lactose and dibasic calcium phosphate dihydrate (DCP) on release of alfuzosin hydrochloride was also investigated. Lactose can act as a channeling agent due to its solubility while DCP can prevent water infiltration for its insoluble nature. Equal amounts of lactose or DCP replaced MCC in the formulations. Lactose containing tablets released alfuzosin faster than MCC and DCP as the release profiles of corresponding formulations were not similar (fmulation  as it te0 is the arithmetic mean response of the 9 runs and bi is the estimated coefficient for Xi (2) was responsible for reducing drug release significantly (p<0.05) at 1, 6 and 12 h. Positive interaction between Methocel and Eudragit was found during 6 and 12 h (The drug release percentages at 1, 6, 12 and 20 h were selected as response variable . These tt for Xi . It was and 12 h . Responsin vitro release of tablets kept at 40°/75% RH were studied according to previously mentioned methods revealed no significant change from initial values (The physical, chemical and l values  which in


Serum testosterone (T) and dihydrotestosterone (DHT) were measured by a sensitive and reliable radioimmunoassay in 42 normal subjects and 33 age-matched patients with carcinoma of the prostate. The mean +/- s.e. for serum testosterone in normal subjects was 16.74 +/- 0.76nM and the corresponding value for patients with carcinoma was 20.94 +/- 1.48nM. Statistical analysis of the results showed a significant increase in T level in patients with carcinoma of the prostate (P less than 0.01). In contrast, there was no difference in DHT concentration between the two groups, values being 2.43 +/- 0.09 and 2.06 +/- 0.09nM for normal subjects and patients respectively. The means +/- s.e. for T/DHT ratio in controls and patients were 6.8 +/- 0.2 and 12.8 +/- 1.3 respectively. The difference was highly significant (P less than 0.001). The wide range of variation for T in patients with carcinoma would suggest that although mean T is higher in these patients, this measurement alone is of little practical value, whereas T/DHT ratio is a more reliable parameter in evaluating the androgen changes in these patients. The significance of these findings in relation to the aetiology of the disease is discussed.


The overall response rate was 25% (95% Cl 19–31). In 10 randomized phase III trials (1769 patients), we studied the role of MMC in combination therapy. A meta-analysis, based on the available published data, failed to show any survival advantage of the MMC containing regimens . Finally, 4 eligible trials (139 patients) assessed the activity of MMC regimens as salvage therapy, 3 in combination with vindesine and one with cisplatin and vinblastine. The overall response rate for the MMC-vindesine regimen was 10.5% (95% Cl 1.7–19.4). In conclusion, MMC is an active drug for NSCLC but does not improve survival when combined with other active drugs, particularly cisplatin. Its use for salvage therapy appears to be associated with marginal activity only. © 2001 Cancer Research Campaign


Left ventricular mass (LVM) is used when expressing infarct or fibrosis as a percentage of the left ventricle (LV). Quantification of LVM is interchangeably carried out in cine steady state free precession (SSFP) and delayed enhancement (DE) magnetic resonance imaging (MRI). However, these techniques may yield different LVM. Therefore, the aim of the study was to compare LVM determined by SSFP and DE MRI in patients and determine the agreement with these sequences with ex vivo data in an experimental animal model.Ethics committees approved human and animal studies. Informed written consent was obtained from all patients. SSFP and DE images were acquired in 60 patients . Ex vivo MRI was used as reference method for LVM in 19 pigs and compared to in vivo SSFP and DE.2 = 0.98), and a bias of 7.3 ± 6.7% (p < 0.001) in pigs (r2 = 0.83). Bias for SSFP and DE images compared to ex vivo LVM was -0.2 ± 9.0% and -7.7 ± 8.5% respectively.LVM was greater in SSFP than in DE (p < 0.001) with a bias of 5.0 ± 6.7% in humans (rLVM was higher when measured with SSFP compared to DE. Thus, the percentage infarction of the LV will differ if SSFP or DE is used to determine LVM. There was no significant difference between SSFP and ex vivo LVM suggesting that SSFP is more accurate for LVM quantification. To avoid intrinsic error due to the differences between the sequences, we suggest using DE when expressing infarct as a percentage of LVM. Myocardial infarct size influences patient prognosis  and leftThe local ethics committee approved the study and written informed consent was obtained from all patients prior to examination. The animal studies were approved by the local animal ethics committee and the study conformed to the Guide for the Care and Use of Laboratory Animals, US National Institute of Health . Sixty patients were included in the study; twenty adults with no signs of myocardial infarct on DE-MRI, 20 adults with myocardial infarct on DE-MRI and 20 children; five of whom underwent cardiac MRI because of suspected myocarditis but had normal findings, and 15 children who had undergone heart surgery for tetralogy of Fallot, but had no signs of fibrosis of the LV. Patient details are presented in Table For comparison of in vivo and ex vivo LVM, nineteen domestic male and female pigs, weighing 40-50 kg, were imaged. After overnight fasting with free access to water the animals were premedicated with ketamine 15 mg/kg  and xylazin 2 mg/kg intramuscularly . Anesthesia was induced with thiopental 12.5 mg/kg  and infusion of fentanyl  was started. Cardiac MRI was performed in vivo after experimentally induced myocardial infarction by inflation of angioplasty balloon in the left anterior descending coronary artery distal to the first diagonal branch. After the animals were sacrificed, their hearts were explanted and imaged ex vivo according to a previously described protocol ,25. See A 1.5 Tesla MRI scanner with a 5-element cardiac synergy coil was used for all in vivo and ex vivo studies . SSFP and DE images were acquired covering the left ventricle from the base to the apex in the short-axis plane. Inversion time was set to null viable myocardium. Typical MRI sequence parameters for SSFP were: echo time 1.5 ms, repetition time 3 ms, flip angle 60°, slice gap 0 mm, slice thickness 8 mm (6 mm in children), inplane resolution 1.1 × 1.1 to 1.6 × 1.6 mm and SENSE factor 2.An inversion recovery GRE-sequence was used to obtain DE images in the short axis plane 10-20 minutes after intravenous administration of 0.2 mmol/kg gadolinium based MR contrast media . Acquisition time for DE was mid diastole. For DE the sequence parameters were: echo time 1.3 ms, repetition time 4 ms, flip angle 15°, slice gap 0 mm and slice thickness 8 mm, inplane resolution 0.9 × 0.9 to 1.6 × 1.6 mm.In vivo imaging of the animals was performed using the same SSFP and DE imaging parameters as in patients. Following euthanasia the animal hearts were removed, the atria excised and the ventricles filled with deuterated water. Ex vivo T1-weighted (T1w) MR imaging was performed with a quadrature head coil covering the left ventricle from the base to the apex, typically resulting in 150 image slices per heart. The sequence parameters were: echo time 3.2 ms, repetition time 20 ms, flip angle 70°, slice gap 0 mm and slice thickness 0.5 mm, inplane resolution 0.5 × 0.5.http://segment.heiberg.se). The LVM was quantified by outlining the endo- and epicardium of the left ventricle in the SSFP, DE and ex vivo images and multiplying the resulting volume by 1.05. Outlining of in vivo images was carried out in end diastole and end systole and the mean value calculated. The papillary muscles were included in the LVM as previously suggested and used in reference values for LVM [All MR images were evaluated by two blinded observers using freely available software +3.5). The difference in LVM between SSFP and DE remained if the 20 patients with myocardial infarct (MI) were excluded +1.7). LVM in the 40 subjects without MI was higher by 6.2 ± 6.9% (p < 0.001) when measured with SSFP compared to DE. In the 20 patients with MI the bias was 2.5 ± 5.5% (p < 0.001).Myocardial mass measured with SSFP images  was higher compared to DE images . The bias for LVM measurement between SSFP and DE images was 5.0 ± 6.7% +30.1) between LVM measured on SSFP and ex vivo T1w MRI  and the difference between the methods was not significant , -28.6),  compared to DE . The bias for LVM measurement between SSFP and DE images was 7.5 ± 6.9%. There was a moderate correlation  and DE sequence and it is possible that other vendors and sequences may yield different results. We did not measure the weight of the LVM in the animals but rather used ex vivo high resolution MRI to obtain the LVM. This could have provided an independent variable for further valuation of the results. The myocardial-to-blood contrast-to-noise ratio was not measured for each subject. However, when acquiring the DE imaging great care was taken to choose the right inversion time to null all viable myocardium. These factors may be considered when performing further studies on this subject.The present study has shown a higher LVM on SSFP compared to DE MRI in patients and animals and that SSFP agrees closely with ex vivo high resolution MRI. We suggest using SSFP when quantifying LVM only, but using mass from DE when presenting infarction as percentage of LVM. The difference in LVM on different MRI sequences found in the present study needs to be considered in future guidelines for quantification of infarct size.The authors declare that they have no competing interests.SSS analyzed all data, and drafted the manuscript. MC analyzed all data and participated in the study design. MU, HE, DE and GO designed and performed the experimental studies. HA conceived the study and participated in its design. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2342/10/4/prepub


High-Risk (HR) and Low-Risk HPV screening was performed using HPV PCR-EIA with genotyping of HR positives and data correlated with age, SDS and cytology. Overall HPV prevalence was 13.5% (9.3% age standardised) and the most frequent HR types were HPV 16, 31, 18 and 58. In HR HPV-positive cases 42.4% had a single HR type and they were predominant in women with severe cytological abnormalities. Here, 66% of all HR HPV cases were in women aged 30 years of age or less and SDS had no significant effect on HPV status. HPV prevalence increased significantly with degree of dyskarosis from 7% in cytology negative samples to 80% in samples with severe cytological abnormalities . Overall, 46% of HR HPV cases were positive for the two HR types targeted by the prophylactic vaccines (HPV 16 and HPV 18). The data presented represents the largest type-specific investigation of HPV prevalence in an unselected UK population.In this cross-sectional population-based study we determine human papillomavirus (HPV) prevalence in South Wales to provide comprehensive baseline data for future assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. Liquid-based cytology samples from women attending routine cervical screening were collected ( Human papillomavirus (HPV) infection is the essential underlying cause of cervical cancer, found in 99.7% of invasive cervical carcinomas . WorldwiMultiple HR types occur in up to 43% of HR HPV-positive women and to date no association has been found between multiple HR types and progression of cervical neoplasia  and Gardasil , both active against HR HPV types 16 and 18 . Currentn=10 000; 20–65 years).We aimed to extend preliminary findings  screening samples were collected in collaboration with Cervical Screening Wales over a 5-month time period in 2004 (non-probability convenience sample). This method included all women attending for routine cervical screening within the catchment area of Llandough Hospital Cytology Laboratory and constitutes a representative sample of the screening population in South Wales. Age, cytology result and Social Deprivation Score (SDS) were provided for each specimen and inadequate cytology samples or those from colposcopy clinics were excluded. The study was approved by South Wales Local Research Ethics Committee.M Tris pH 7.4. 10 μl of recombinant proteinase K was added to a 100 μl cell suspension from each sample, incubated at 56°C for 2 h, followed by 100°C for 10 min. Samples were refrigerated (4°C) for 10 min, centrifuged at 13 000 r.p.m. for 10 min and the supernatant transferred into a 96-well plate. A PCR for the human β-globin gene was performed on every DNA sample to determine extraction efficiency as described earlier  and negative (water) DNA extraction, PCR and ELISA controls were included for every 94 samples. Re-analysis of 10% of all samples processed was undertaken for internal quality assessment purposes. Results were analysed in an automated Excel worksheet and raw data from each reading at each time point pasted into a specific position in the datasheet and results are then given as positive (1) or negative (0). The negative extraction control included in every 96-well plate serves as the background reading for which all the other results are compared. A positive result is equivalent to three times background.The LBC samples (Thinprep) were processed by the Cytology Laboratory according to the British Society of Clinical Cytology guidelines . Residuaβ-globin PCR positive; complete information available on age, cytology result and SDS; within the screening age group 20–65 years. The HR HPV prevalence was age-standardised using the European Standard Population and the age-standardised rate calculation ∑ Si ria/∑ Si  were calculated where appropriate. All HR HPV-positive cases were differentiated into those with a single HR type and those with multiple HR types.Statistical analysis was performed on samples that complied with the following inclusion criteria: ria/∑ Si . Social ria/∑ Si . The oveThe mean age was 38 years with 29.4% aged between 20–29 years, 25.8% 30–39 years, 23.4% 40–49 years, 15.8% 50–59 years and 5.6% over 60 years old. In this study population, 93% were cytology negative, 4.7% had borderline changes and 1.4, 0.5 and 0.52% had mild, moderate and severe dyskaryosis respectively. The distribution of samples according to SDS based on the LSOA ranking system was 9.5% from the 10% most deprived; 5.6% from the 10 to 20%; 7.4% from the 20 to 30%; 12.6% from the 30 to 50%; and 64.8% from the 50% least deprived LSOA in Wales.β-globin-positive DNA extraction controls and 96% reproducibility for HR and LR HPV-positive results. Here, 1015 HR HPV-positive and 209 LR HPV-positive cases were identified. In the 1015 HR HPV-positive cases there were 2007 HR infections and 157 were also positive for LR HPV. Overall HPV prevalence was 13.5%  with an age standardised HPV prevalence in the South Wales population of 9.3%.Of the 10 000 samples processed, 921 did not meet the inclusion criteria and full statistical analysis was performed on the remaining 9079 samples. Internal quality assessment indicated 93% reproducibility for n=1015) the most prevalent HR genotypes detected were 16 (31.4%), 31 (22.6%), 18 (21.7%) and 58 (19.8%). The proportion of HR HPV cases attributable to types included in currently licensed prophylactic HPV vaccines (HPV 16 and HPV 18) was 46% overall (n=471 out of 1015) and 70% (n=28 out of 40) for cases with severe cytological abnormalities. Here, 42%  of HR HPV-positive cases had an infection with a single HR type and in these women HPV 16 was the predominant genotype (n=143 out of 430). The remaining 58%  had multiple HR types and HPV 18 was the most predominant type detected (n=201 out of 585). The prevalence of each HPV genotype in cases with a single HR infection was compared with cases containing multiple HR types and no statistically significant differences were found for HPV 16, 51 or 66 . All other genotypes were statistically significantly more common in cases with multiple HR types compared with those with a single HR type .In HR HPV-positive cases ( HR type . In casen=262 out of 430) and cases with multiple HR types (n=411 out of 585) were found in women aged 30 years or less. Cases with multiple HR types were more common than single HR cases in all women upto 44 years and this was statistically significant in women aged 30 or less .Here, 66% of all HR and 57.6% of LR HPV cases were found in women aged 30 years or less and the prevalence of HR cases decreased progressively with age from 29.4% at 20–24 years to 1.4–2% at ages 50–65 years . In concn=8434), borderline (n=426), mild (n=126), moderate (n=43) and severe (n=50). There was a statistically significant increase in the proportion of HR HPV-positive cases from 7% (n=590 out of 8434) in cytology negative samples up to 80% (n=40 out of 50) with severe dyskaryosis (P<0.0001). There was a limited variation between total HR HPV prevalence in cases with borderline, mild, moderate and severe dyskaryosis because of the many cases with multiple HR types in all grades with abnormal cytology. In contrast, cases with a single HR type predominated in women with severe dyskaryosis and this was significant relative to their prevalence in negative, borderline, mild and moderate cytology samples . Severe cytological abnormalities were detected in 50 cases and 40 out of 50 were also HR HPV positive: 21 out of 40 cases contained a single HR HPV infection 14 of which were positive for HPV 16 and in the remaining 19 out of 40 cases with multiple HR types 11 were HPV 16 positive. Here, 25 of the 366 LR HPV cases detected in this study population had an abnormal cytology .HPV prevalence by cytology grade was calculated as a percentage of the total number of women in the study population classified as negative (Most of the women in the study were from the 50% least deprived LSOA (64.8%) and the lowest HR HPV prevalence was detected in the 50% least deprived LSOA in Wales (10.5%) with the highest in the 10% most deprived LSOA (13.3%) according to SDS. However, HR HPV cases were not significantly more prevalent in any one rank .This is the largest type-specific investigation of HPV infection in an unselected UK population to date, with an overall HPV prevalence of 13.5% (9.3% age standardised). This baseline HPV data was particularly robust for two reasons: (i) Samples were anonymous and therefore did not require consent allowing collection of consecutive samples from all women attending routine cervical screening; (ii) A two-tier typing procedure was followed in which HR-positive samples were identified and then validated with a second HPV PCR before typing for 14 individual HR HPV types, thus reducing the risk of false positive results. Stringent quality control procedures were also employed involving random retyping of 10% samples.Within Europe, the closest comparative study was in Scotland  of these women were aged 30 years or less and more recent studies have observed an increasing number of multiple infections within this age group (The highest HR HPV prevalence was found in women aged 30 years or less consistent with other findings (The use of an anonymous screening population avoids many potential sources of bias. However, it inevitably only includes people who attend for their smears and we do not have data on the HPV status of non-attendees. The reported correlation of increased cervical cancer incidence associated with social deprivation (We identified HPV 16, 31, 18 and 58 as the predominant HR types, which is broadly consistent with other studies . Our datIn summary, current prevalence of HPV infection in South Wales is 13.5% and half of all current HR HPV cases would be targeted by the prophylactic HPV vaccines.


To describe sexual and HIV/sexually transmitted infection (STI) risk behaviours in Slovenia.A nationally representative cross-sectional survey of the general population aged 18–49 years in 1999–2001 was conducted. The data were collected by face-to-face interviews and anonymous self-administered questionnaires. Statistical methods for complex survey data were used.849 men and 903 women were interviewed. In the past 5 years, both men and women reported a median of one heterosexual partner , concurrent heterosexual partnerships were reported by 24.4% of men and 8.2% of women, heterosexual sex with non-Slovenian partners by 12.6% of men and 12.2% of women, forced sex by 4.8% of women, paid heterosexual sex by 2.6% of men, sex with another man by 0.6% of men and heterosexual sex with an injecting drug user by 1.2% of men and 1.3% of women. In the past year, 22.7% of men and 9.5% of women reported forming at least one new heterosexual partnership. The mean numbers of episodes of heterosexual sex in the previous 4 weeks were 6.1 for men and 6.0 for women. Consistent and inconsistent condom use was reported more frequently among men reporting multiple female partners and those not married or cohabiting.Recent patterns of reported sexual behaviour are consistent with a low risk of HIV and STI transmission in Slovenia. The results will inform Slovenian sexual health policies including HIV/STI prevention, and are particularly valuable because population-based data on HIV/STI risk behaviour have not previously been available in low HIV prevalence countries of central Europe. Chlamydia trachomatis infection among 18–24 year olds as 4.1%, indicating gaps in prevention, diagnosis and treatment.5Slovenia is one of the low HIV prevalence countries of central Europe with less than one infected individual per 1000 population.–Reliable data on patterns of sexual behaviour are needed to inform sexual and reproductive health policies, including those for the prevention of HIV and STI. In the late 1980s and early 1990s, almost all western European countries, and many other developed and developing countries, conducted nationally representative sexual behaviour surveys.6We used stratified two-stage probability sampling of 18–49-year-old Slovenians based on the central population register. Data were collected between November 1999 and February 2001 at respondents’ homes by face-to-face interviews and anonymous self-administered pencil and paper questionnaires. Questionnaires adapted from the British National Survey of Sexual Attitudes and Lifestyles (NATSAL) conducted in 199014Weights were computed to adjust for differences in survey response and any remaining differences between the achieved sample and available Slovenian population estimates according to statistical regions, types of communities, gender and age groups, based on central population register data for the year 2000.2 test based on F statistics using a second-order Rao and Scott correction accounting for the survey design.Response rates were calculated from unweighted data. Other analyses were conducted using statistical methods for complex survey data to account for stratification, clustering and weighting, using STATA version 7.0. Age at interview was grouped as 18–24, 25–34 and 35–49 years, corresponding almost exactly with birth cohorts 1975–82, 1965–74 and 1950–64. Weighted proportions with 95% CI were computed for different reported behaviours, stratified by gender, age group and marital status when appropriate. Tests for heterogeneity of proportions were computed using the Pearson χEthics approval was obtained from the ethics committees of the Ministry of Health of the Republic of Slovenia and the London School of Hygiene and Tropical Medicine.We interviewed 1752 individuals aged 18–49 years. The overall survey response rate was 67.0%. Concurrent partnerships at least once during their lifetime were reported by 35.3% (95% CI 31.5% to 39.3%) of men and 15.3% (95% CI 12.8% to 18.2%) of women and during the past 5 years by 24.4% (95% CI 21.3% to 27.8%) of men and 8.2% (95% CI 6.6% to 10.3%) of women. For all periods and all age groups, men consistently reported concurrency more frequently than women (p<0.05), except for 18–24 year olds for the past year (p = 0.07). As the proportion of respondents with concurrent heterosexual relationships over their lifetime is influenced by the number of sexually active years, the reporting of lifetime concurrent partners was more common in older than younger men. In contrast, women aged 18–24 years reported having ever engaged in concurrent relationships with similar frequency (17.4%) as women aged 25–34 and 35–49 years .Coercive sex was not uncommon. Women were asked “when, if ever, was the last time a man forced you into sexual intercourse” and 12.0% (95% CI 9.8% to 14.5%) of women reported having ever been forced and 4.8% during the past 5 years.Overall, 4.4% (95% CI 3.1% to 6.4%) of men reported having ever paid for sex with a woman; 2.1% (95% CI 1.2% to 3.4%) of men reported only one occasion of paying for sex with a woman during their lifetime, but 0.9% (95% CI 0.4% to 2.0%) reported at least 10 such occasions. The mean numbers of heterosexual encounters paid for increased from 0.1 in those aged 18–24 years to 0.4 and 0.3 among older men . Overall, 3.4% (95% CI 2.3% to 5.0%) of men had paid for sex with a foreign women at least once. Respondents were also asked whether they had ever received payment for sex; 0.9% (95% CI 0.4% to 2.1%) of men (no MSM) and 0.6% (95% CI 0.3% to 1.3%) of women responded that they had. Among women aged 18–24 years, 1.6% (95% CI 0.7% to 3.8%) reported receiving payment for sex, suggesting a recent increase in selling sex among the youngest (p = 0.05).Sex with a non-Slovenian heterosexual partner during the past 5 years was reported by 12.6% (95% CI 10.1% to 15.6%) of men and 12.2% (95% CI 9.8% to 15.1%) of women. Recent non-Slovenian heterosexual partners of both men and women were most often casual , followed by spouses , steady partners  and for men, commercial sex workers (6.2%). The last heterosexual sexual intercourse with a foreign partner occurred abroad in 48.7% of instances for men and 25.9% of instances for women, only in 5% of instances in countries outside Europe.Men and women reported similar frequencies of heterosexual intercourse in the past 4 weeks. For both genders, the frequency of sex was lowest among the youngest age group (p<0.001). As marriage or cohabitation implies the availability of a regular sexual partner, the frequency of heterosexual intercourse was much higher in this group than in those previously married and single (p<0.001 for both genders).Vaginal intercourse was almost universal . LifetimA small proportion of men  and women  reported having had a sexual experience or sexual contact  with someone of the same gender. Intercourse with someone of the same gender  during their lifetime was reported by 1.0% (95% CI 0.5% to 2.0%) of men and 0.9% (95% CI 0.5% to 1.9%) of women. At the time of the survey, the majority of men who reported ever having had sex with men were married or cohabiting with a female partner.Overall, 11.6% (95% CI 9.2% to 14.4%) of men and 9.1% (95% CI 7.2% to 11.5%) of women reported consistent condom use during vaginal or anal heterosexual intercourse in the past 4 weeks, and an additional 14.7% (95% CI 11.9% to 18.1%) of men and 9.9% (95% CI 7.9% to 12.3%) of women inconsistent use. Consistent and inconsistent condom use were reported more frequently among men and women who were single, separated, divorced or widowed than married or cohabiting (p<0.05) . SimilarLifetime injection of illicit drugs was reported by 0.3% (95% CI 0.1% to 1.1%) of men and 0.1% (95% CI 0.0% to 0.6%) of women and was most common among those 18–24 years old, reported by 0.7% (95% CI 0.2% to 2.6%) of men and 0.4% (95% CI 0.1% to 2.7%) of women. Individuals who injected drugs (IDU) during their lifetime reported higher numbers of lifetime heterosexual partners than non-users . All IDU reported that their most recent heterosexual partners have never injected illicit drugs. Among individuals who reported having never injected illicit drugs themselves, 1.2% (95% CI 0.7% to 2.0%) of men and 1.3% (95% CI 0.8% to 2.1%) of women reported having had a heterosexual partner in the past 5 years who had injected illicit drugs.Our results provide the first estimates of sexual behaviour, HIV/STI risk and recent condom use behaviours in the general population of Slovenia, and show wide variability in sexual lifestyles between individuals of different ages, men and women and according to marital status.Our results are comparable to the British survey , as we used similar methods and collected the data at the same time in a probability sample of the general population, but with a slightly different age range .Population-based data on HIV/STI risk behaviour have not previously been available in low HIV prevalence countries of central Europe.Recent patterns of reported sexual behaviour in a nationally representative cross-sectional survey of 18–49 year old Slovenians are consistent with a low risk of HIV/STI transmission.In the past 5 years, men and women reported 3.2 and 1.5 mean numbers of heterosexual partners and 24.4% and 8.2%, respectively, reported concurrent heterosexual partnerships.Consistent and inconsistent condom use was reported more frequently among men reporting multiple female partners and those not married or cohabiting.Other national sexual behaviour surveys conducted in the late 1980s and 1990s in probability samples of the general populations of west European countries also reported higher mean numbers of lifetime sexual partners than our data ; higher proportions of men who had ever paid women for sex  and higher proportions of men reporting at least one male sexual partner , with the exception of Portugal (0.9%).16–21Other similar surveys also reported striking gender differences in the reported numbers of heterosexual partners, which may be explained partly by social and cultural factors resulting in a tendency for men to over-report and women to under-report, by a small number of women with very high numbers of male partners and who may be underrepresented in the sample  and from age mixing, as women marry or start cohabiting at a younger age and tend to choose older partners.17For people from low HIV and STI prevalence countries, engaging in sex with people from higher prevalence countries increases risk.Sex with someone of the same gender was reported rarely. As MSM have the highest HIV prevalence in Slovenia and bear a disproportionately high burden of other STI,As consistent and correct use of condoms significantly reduces the risk of HIV, other STI and unplanned conception, condom use has been promoted in Slovenia as in other parts of the world. We have previously reported the steep increase over time in condom use at first heterosexual intercourse and the association with the increased likelihood of use later in sexually active life, suggesting that HIV-related condom use promotion has had an impact on preventive behaviours.26Under 1% of Slovenian men and women aged 18–24 years reported injecting illicit drugs during the past 5 years, similar to estimates from comparable European surveys.The methodological strengths of our survey include a reliable general population sampling frame and the use of extensively pre-tested and piloted data collection methods. The use of anonymous self-administered questionnaires may have contributed to the improved validity of self-reported information. Limitations include validity constraints on self-reported information and possible participation biases. We may have underestimated the proportions of individuals with particular higher-risk behavioural patterns that tend to be more stigmatised, for example, the proportion of MSM. However, reluctant respondents who agreed to participate only after prompting and those who responded to the first request for participation do not always show differences with respect to sexual practices.29To conclude, recent sexual behaviour, HIV/STI risk and condom use behaviour patterns indicate a low risk of HIV/STI transmission in the general population of Slovenia. Our results will inform Slovenian sexual and reproductive health policies including HIV/STI prevention, and are particularly valuable, because nationally representative population-based HIV/STI risk and sexual behaviour data have not previously been available in low HIV prevalence countries of central Europe.21


We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995.in situ incidence increased 1.7-fold during 1995–2000, and decreased by 19.6% during 2000–2006.The invasive cancer incidence decreased by 47.8% during 1995–2006. The carcinoma The Taiwan national programme has significantly decreased invasive cervical cancer. Cervical cancer has been one of the most serious cancers in Taiwan over the last three decades, accounting for more than 20% of all female cancers before 2001, and for over 10% of female cancer deaths before 1995 . Such reThe specific aim of this study is to evaluate whether the disease burden of cervical cancer changed with the implementation of national screening programme in Taiwan, where the screening participation was lower than those in other countries with organised screening programme.In this study, cervical cancer incidence and mortality data were derived from several national registries. Population numbers during 1991–2007 were obtained from National Household Registry profiles ; this wain situ were differentiated according to the ICD-O-FT or ICD-O-3 morphology fifth digit behaviour code for neoplasms. The identification of cancer cell type was according to ICD-O-FT or ICD-O-3 morphology code.National Cancer Registry in Taiwan was launched in 1979 to collect information of all incident cancer cases from hospitals with 50 or more beds. It was considered a complete and accurate registry with a percentage of cases based on death certificate only (DCO) as low as 3.9% in 2000 and 1.8% in 2005. The DCO percentage for cervical cancer was <1% after 2000, and the percentage of morphological verification of cervical cancer was more than 90% after 2002 . The numThe National Health Insurance was implemented in Taiwan in 1995, covering 90–98% of the general population; it started to reimburse annual conventional Pap smear for women over 30 years of age in 1995. The National Cervical Cancer Screening Registry was also launched in 1995 to evaluate the efficacy and effectiveness of the programme. All Pap smears were reviewed according to 2001 Bethesda system . Age-adjusted incidence of carcinoma in situ per 100 000 women increased from 23.9 in 1995 to 69.2 in 1999, and then decreased from 69.2 to 52.4 (24.3% reduction). The age-adjusted incidence of invasive cancer and carcinoma in situ rapidly reduced in 2003 and rebounded in 2004 might be due to reduction in screening and confirmatory diagnosis of cervical cancers because of the outbreak of severe acute respiratory syndrome in 2003 in Taiwan.The secular trends of age-standardised cervical cancer incidence for women aged 30 years or more in Taiwan are shown in in situ increased rapidly after 1995, picked at 1999, and then reduced in most age groups except the age group of 30–39 years.The incidence of invasive cervical cancer did not decrease significantly in age groups of 30–69 years until 1997 and in age group of 70+ years until 1999. The reduction percentage of incidence of invasive cervical cancer from 1995 to 2006 was 47.5% (from 20.0 to 10.5), 41.9% (from 43.2 to 25.1), 54.8% (from 67.7 to 30.6), 55.5% (from 83.1 to 37.0), and 32.3% (from 77.1 to 52.2), respectively, for age group of 30–39, 40–49, 50–59, 60–69, and 70+ years. The incidence of carcinoma The main morphological type of invasive cervical cancer in Taiwan was squamous cell carcinoma, but the proportion of adenocarcinoma increased from 5.5% in 1991 to 13.7% in 2006. The incidence of invasive cervical squamous cell carcinoma decreased from 1995 to 2006 showing a reduction percentage of 55.6% (from 16.0 to 7.1), 48.1% (from 34.1 to 17.7), 58.5% (from 56.2 to 23.3), 53.7% (from 67.2 to 31.1), and 31.0% (from 64.2 to 44.3 per 100 000), respectively, for age groups of 30–39, 40–49, 50–59, 60–69, and 70+ years. The incidence of invasive cervical adenocarcinoma decreased from 2000 to 2006 showing a reduction percentage of 15.4% (from 2.6 to 2.2), 31.3% (from 6.4 to 4.4), 21.0% (from 6.2 to 4.9), 31.9% (from 4.7 to 3.2), and 7.9% (from 3.8 to 3.5 per 100 000), respectively, for age groups of 30–39, 40–49, 50–59, 60–69, and 70+ years.The study provided evidence that national organised screening programme significantly reduced cervical cancer risk in Taiwan. We used several complete and accurate national databases to assess efficacy. The significant rapid and gradual reduction observed in this study was obviously attributable to the programme. Organised cervical cancer screening is well-known to effectively reduce invasive cancer incidence in developed countries, and consistent findings were observed in this study. There was 48.0% reduction in invasive cancer incidence from 1995 to 2006 in women with an average triennial screening participation of 53.4% after 2000. Compared with the slow reduction in incidence before the national screening programme, the rapid reduction after the screening programme provides evidence for its efficacy.in situ also significantly reduced in all age groups older than 35 years.The screening may decrease the incidence of invasive cancer by detecting precancerous lesions. The incidence of invasive cancer in regions with more than 70% triennial screening participation reduced at least 35% after 10 years of organised screening, but 52% triennial participation in Taiwan only reduced 28.9% (in situ as precancerous lesions facilitated early detection of malignant lesions (In this study, the screening programme significantly reduced the incidence of squamous cell carcinoma and adenocarcinoma in all age groups. A recent study of cervical adenocarcinoma incidence in 13 European countries . However


Etoposide phosphate is a water-soluble prodrug of etoposide. It was expected that this prodrug could be used to overcome the solubility limitations and erratic bioavailability of oral etoposide. To investigate the possibility of prodrug conversion to etoposide within the gastrointestinal lumen, etoposide phosphate was dissolved in water and incubated with human gastric juice or human bile in vitro. Samples were collected during 150 min and analysed for etoposide concentration with high-performance liquid chromatography. Conversion of prodrug to etoposide during incubation with gastric juice was negligible. There was significant conversion during incubation with bile at pH 7-8. The percentage of prodrug converted to etoposide at pH 8 after 60 min was 78 +/- 18% (mean +/- S.D.) for a 0.1 mg ml-1 prodrug solution and 36 +/- 26% for 0.5 mg ml-1. At pH 7, after 60 min 22% of prodrug was converted to etoposide when incubated at 0.1 mg ml-1 and 10% at 0.5 mg ml-1. No conversion was found after inactivation of alkaline phosphate (AP) by overnight heating of bile at 65 degrees C or by the addition of disodium edetate to the bile. In conclusion, because of AP in bile, variable conversion of etoposide phosphate to etoposide can be expected within the intestinal lumen after oral administration. This could have important pharmacokinetic consequences.


The severity of aortic regurgitation (AR) can be determined by invasive or echocardiographic methods. We systematically compared quantitative invasive and echocardiographic data with semiquantitative invasive grades in a prospective series of patients. Using Doppler-echocardiography we determined the cardiac output over the aortic, pulmonary and mitral valve in 27 patients . Aortic regurgitant volume was calculated as the difference between the cardiac output over aortic and pulmonary valve/ mitral valve. During angiography the severity of AR was assessed semiquantitatively by aortography and the regurgitant volume was calculated invasively as the difference between the left- and right ventricular cardiac output. The echocardiographically and invasively determined regurgitant blood volume correlated closely (R≈0.8). The regurgitant volume increased with higher angiographic grade but there was significant overlap between adjoining qualitative grades. In patients with AR, quantitative echocardiographic and angiographic measurements of the regurgitant volume correlate closely. The natural history of aortic regurgitation (AR) is characterized by an asymptomatic period of left ventricular compensation followed by decompensation with eventually irreversible left ventricular dysfunction. The management of patients with AR and in particular the timely indication of valve surgery is therefore dependent on a reliable estimation of the severity and progression of regurgitation and LV function . The sevBetween July ‘90 and May ‘93 we examined 136 consecutive patients who were referred to the color imaging laboratory of the Philipps-University-Marburg for further evaluation of suspected valvular disease. All patients had undergone 2D and conventional Doppler studies before referral. Informed consent was obtained according to institutional guidelines. The study was approved by the Philipps-University Marburg. Fourty-four patients were excluded from the final analysis for the following reasons: no reliable visualization (n=2), pulmonary valvular disease or combined aortic valve disease (n=6), mitral valve disease (n=24), atrial septal defect (n=9), ventricular septal defect (n=3). Of the remaining 92 patients, only those 27 patients that were examined by cardiac catheterization and echocardiography within 24 hours were included in this study. Twenty of these patients had AR and 7 did not. The patients with AR had no concomitant, significant aortic stenosis . The 7 patients in the control group had the following diseases: dilated cardiomyopathy (n=2), CAD (n=2), HTN (n=2), mitral valve prolapse without regurgitation (n=1).Access was established using the Seldinger technique from a femoral artery. After coronary angiography a 7F pigtail catheter was placed in the mid left ventricle. A left ventriculogram was recorded in the 30 degree RAO projection over several cardiac cycles. The catheter was then withdrawn into the ascending aorta for the aortography in a 30 degree RAO projection. For both ventriculography and aortography, 40 ml of contrast material were injected with a flow of 14 ml/sec.The semiquantitative grading of AR was done according to established guidelines . Grade 1The images of the ventriculogram were analyzed off line. End-diastolic and end-systolic frames were chosen for planimetry. The pictures were projected from a projector Tagano 35 CX) onto a calibrated screen. The heart base, the maximal length of the ventricular cavity and the left ventricular circumference were manually traced on the screen. The left ventricular stroke volume (LV) was calculated according to the area-length method  CX onto . The resvia a femoral vein with a pulmonary artery flotation catheter. The tip of the catheter was positioned in the main stem of the right pulmonary artery. Through the proximal sidehole 10 ml 0.9% NaCl at room temperature were injected. At the thermistor at the distal end of the catheter the temperature were recorded.The right heart catheterization was performed The right ventricular (RV) cardiac output was calculated semiautomatically according to the Stewart Hamilton equation ,8.The invasive regurgitant volume (RVinvasive) was calculated as the difference between the left- and right-ventricular cardiac output (LVCO/RVCO) determined by ventriculography (LVCO) and thermodilution (RVCO).All examinations were performed by an experienced physician sonographer, who was blinded to the results of the cardiac catheterization. The examinations were performed with a Sonotron Vingmed CFM750 machine, equipped with an imaging transducer of 3.5 or 2.75 Megahertz for the M-mode and 2D images. The echo-machine was connected online with a Macintosh Apple III personal computer equipped with an image processing software package. For off line analysis, the images were stored on optical disk and also printed on paper and recorded on a video recorder.3).The examination was performed in a left decubitus position. Complete 2D, conventional Doppler and color Doppler study with evaluation of all valves and ventricular function were performed according to ASE standards. The cross sectional areas (CSA) of the aortic, pulmonic and mitral valve were determined using the formula CSA = πr2 as follows: The maximal diameter of the left ventricular outflow tract (LVOT) was measured from a 2D-parasternal long axis view. The maximal diameter of the pulmonary artery (PA) was measured from a 2D-parasternal short axis view at the level of the pulmonic valve. The maximal diameter of the mitral valve (MV) was measured from a 2D apical 4-chamber view at the level between the mid and distal third of the valve leaflets .The flow velocity was measured by pulsed Doppler. It was measured in a parasternal short axis view for the pulmonary valve with the sample volume directly distal of the valve. For the aortic valve it was measured from an apical 5-chamber view with the sample volume in the LVOT . For the mitral valve flow velocity was measured from a apical 4-chamber view with the sample volume at the level of the mitral valve, respectively  was calculated semiautomatically by planimetry. For each valve, 3 representative cycles that followed a sinus beat were analyzed, and the results averaged. The stroke volume was calculated according to the formula -13.The cardiac output (CO) was calculated by multiplying stroke volume (SV) and heart rate (HR):The regurgitant volume (RVecho1) was calculated as the difference between the cardiac output of the aortic and pulmonary valve .RVecho2 was calculated as the difference between the cardiac output of the aortic and mitral valve .For all measurements the mean, standard deviation and ranges are described.Comparisons of the results were made by paired and unpaired t-test for paired and unpaired data, respectively. Simple linear regression analysis was employed to test the relation between two continuos parameters. Spearman rank correlation was used for the comparison of discrete angiographic grades and continuos parameters.Mean age was 49.4±12.6 (23-69) years. Eighteen (66.7%) patients were male. Mean EF was 60.5±17.8%. LVEDd was 5.9±1.1 cm (4.1-7.7), LVESd was 4.0±1.01 cm (2.4-6.4). All patients were in normal sinus rhythm at the time of examination. The mean heart rate during catheterization was 73.9±14.4 bpm and during echocardiography 70.3±20.2 bpm.In the 20 patients with AR the cardiac output over the aortic, pulmonary, and mitral valve were: 9.4±3.2 l/min (5.5-17.0), 4.72±1.1 l/min (2.7-7.3), and 5.1±1.1 l/min (3.3-7.4), respectively.In the 7 patients without AR the cardiac output over the aortic, pulmonary, and mitral valve were: 5.3±1.2 l/min (3.7-7.1), 5.1±1.1 l/min (3.5-7.3), and 5.1±1.4 l/min (3.3-7.8), respectively.The calculated regurgitant volume in patients with AR was 4.7±2.7 (1.4-10.8) for the comparison of the aortic and pulmonary valve (RVecho1) and 4.3±2.6 (0.01-10.3) for the comparison of the aortic and mitral valve (RVecho2).The calculated regurgitant volume in patients without AR was 0.2±0.8 (-0.8-1.6) for the comparison of the aortic and pulmonary valve (RVecho1) and 0.3±0.9 (-0.7-1.7) for the comparison of the aortic and mitral valve (RVecho2).Semiquantitative grading of aortic regurgitation by aortography showed grade 0 in 7 patients (26%), grade 1 in 1 patients (4%), grade 2 in 8 patients (30%), grade 3 in 9 patients (33%) and grade 4 in 2 patients (7%).In the 20 patients with AR the right-and left-ventricular cardiac output were 5.9±1.3 l/min (3.6-9.0) and 10.7±3.8 l/min (6.0-19.8), respectively.In the 7 patients without AR the right-and left-ventricular cardiac output were 5.0±0.9 l/min (3.5-6.6) and 5.1±1.7 l/min (2.7-7.3), respectively.In the 20 patients with AR the calculated regurgitant volume was 4.7±3.3 l/min (0.81-12.8).In the 7 patients without AR the calculated regurgitant volume was 0.06±1.1 l/min (-1.9-1.3).Comparison between Echocardiographic and Invasive MethodThe regurgitant volume calculated from aortic and pulmonary valve (RVecho1) was compared to the regurgitant volume calculated from aortic and mitral valve (RVecho2). For the entire group, the correlation was 0.98; p<0.0001; y= 0.93x-0.011; SE= 0.038.The echocardiographic regurgitant volume RVecho1  and RVecho2  were compared with the angiographic regurgitant volume (RVinvasive). For RVecho1 the correlation was 0.8; p<0.0001; y=0.69x+1.07; SE= 0.10.For RVecho2 the correlation was 0.78; p<0.0001. y=0.64x+0.99; SE=0.10.1 shows the comparison of the RV calculated by echocardiographic and invasive method and the angiographic grades. There was a significant correlation between higher grades of severity and increased RVecho 1 , RVecho2 , and RVinvasive .Table However, because of a wide range of the regurgitant volume in each grade, no significant differences of the echocardiographic RV was found between angiographic grades 2 and 3. In this study we systematically compared quantitative echocardiographic, quantitative invasive and semiquantitative invasive data determining the severity of aortic insufficiency. We found a high correlation (R=0.98) between two quantitative echocardiographic methods quantifying the regurgitant volume over the aortic valve (RVecho1 and RVecho2). Although the correlation between angiographic and echocardiographic quantitative methods was good, the correlation between semiquantitative angiographic grades and RV was only moderate and semiquantitative grading could not differentiate grade 2 and 3 because of significant overlap between grades.Echo and semiquantitative grades , with significant overlap between grades. Rokey et al. examined 6 patients with isolated AR and 19 patients with isolated MR [These results have important implications for the approach to patients with AR. The angiographic semiquantitative classification has been the historical “gold standard” for estimating severity of AR and grade 3 has been used as a cutoff point above which to consider valve surgery. Our results suggest that angiographic grades 2 and 3 do not reliably differentiate groups with different hemodynamically active regurgitant volume. This is consistent with results of previous studies. Kitabatake examined 10 patients with isolated AR, 13 with additional valve disease and 10 control patients . Using dlated MR . Mitral lated MR . The autThese and other studies  describePrevious studies generally report a good correlation between echocardiographic, szintigraphic and invasive quantitative methods determining RV: Kitabatake calculated the regurgitant fraction (RF) invasively from right ventricular stroke volume, determined by thermodilution and left ventricular stroke volume determined by ventriculography . A closeIn calculating the cardiac output over individual valves by multiplying the velocity time integral (VTI) and the outflow tract area several technical limitations have to be considered: The calculation of the outflow tract area from one measured diameter assumes a circular shape during systole. Several studies have shown a nearly circular anatomy of the aortic and pulmonary valves and a constant valve area during systole -20. On tThe goal of our study was to compare noninvasive, echocardiographic quantification of aortic insufficiency versus quantitative and qualitative invasive methods. We did not perform a comparison of the described echocardiographic quantitative method to a comprehensive echocardiographic evaluation as performed typically in clinical practice. This typically includes flow mapping to determines the spatial extension of the regurgitant jet -31, the However, as quantification of flow events has more recently been described using three dimensional echocardiography ,39 and mqualitative results obtained with 2D Echo and quantitative echocardiographic results and clinical findings is therefore necessary.The small number of patients is a major limitation of our study. Also, the regurgitant volume is dependent on hemodynamic conditions. Therefore the time delay between echocardiographic and invasive examination may have affected the correlation between echocardiography and angiographic grades. In order to minimize that influence we included only patients who had the two examinations within 24 hours. The results of the RV calculated in patients without AR show a relative large range with both echocardiographic and invasive calculation. A careful comparison of The results of our study show a good correlation between echocardiographic and invasive quantitative calculations of the regurgitant volume in patients with aortic insufficiency. The comparison to the semiquantitative angiographic grades show that grades 2 and 3 do not reliably differentiate groups with significant different regurgitant volume. Although angiographic grading of severity is considered the traditional “gold standard”, management decisions in patients with aortic regurgitation should therefore not rely on angiographic grades alone but incorporate a quantitative assessment of the hemodynamically active regurgitant volume.


Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV) transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa.We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined.KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73) was nearly twice that of HIV (44.6% vs. 23.1%). HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities.The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission. Kaposi Sarcoma-associated herpesvirus (KSHV), also known as Human Herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma (KS) ,2, and iThe biological, social and environmental factors involved in non-sexual horizontal transmission of KSHV are still largely unknown. The HIV epidemic has had a profound effect on the rate of KS development in Africa. In South Africa, HIV co-infection is associated with up to 50 fold increases in risk for developing KS . The rolHIV seroprevalence in pregnant women attending public sector antenatal clinics has been used as a reliable gauge of the South African HIV epidemic ,22. Unde2. It is mostly urbanized and is home to over 9.6 million people, over a fifth of the national population . The μg (σg) for latent orf73 was 0.40 (0.11 - 0.76) and did not differ significantly between regions (4df = 0.0675P) or education levels (3df = 0.0874P). HIV positive women had significantly higher lytic and latent KSHV antibody levels than HIV negative women (μg (σg): 1.0(0.50 - 1.69) vs. 0.70(0.28 - 1.27), (1df < 0.0001P) and 0.54(0.21 - 0.98), vs. 0.36(0.09 - 0.68), respectively) (1df < 0.0001P) (Table The geometric mean (μtrend = 0.5988P) (Table trend = 0.0015P) being protective against KSHV but not HIV infection. More than half (53.0%) of the 117 women with no formal education (< 2 years) were seropositive to KSHV decreasing to 41.7% in the 959 women with the highest high school matriculation certificate (3df = 0.008P). The number of pregnancies and live births had no effect on KSHV seropositivity. (Table Seropositivity to KSHV in these women in their reproductive years was not associated with age (8) Table . While ocation <  years weThe overall seroprevalence of HIV and syphilis, in pregnant women across all the clinics was 23.1% and 17.1%, respectively. Overall, 34.6% of all the women had either HIV or syphilis but only 6% were infected with both. Seropositivity to KSHV was 69.7% in HIV infected women and 37.1% in uninfected women (p < 0.0001) (Table 4df = 0.0015P)  Table . Risks o5) Table . While t5) Table .1df = 0.4, Table To further explore this geographic variation in KSHV serology within this region, we looked at the river catchments within the different regions. It was clear that there were two main river catchment systems draining south and north Figure . KSHV seAlthough HIV prevalence in South African women attending public sector antenatal clinics is well described , little In this study, KSHV seroprevalence in pregnant women attending antenatal clinics in the Gauteng province of South Africa was very high (45%) and nearly double that of HIV infection (23%). This further confirms that KSHV infection is very common in Southern African women consistent with previous reports where reported prevalence ranged from 30% - 46% ,26. HIV The lack of association between KSHV and age noted in this study may be attributed to the narrow age range studied (mean (± SD) 25.9 (6.2)). In this study, pregnant women with a higher level of education had lower rates of KSHV infection. The association between KSHV and increasing education has been shown in other studies . EducatiWe observed significant variation in the prevalence of KSHV between the regions within the Gauteng province of South Africa which remained after adjustment for several factors including age, HIV, syphilis status and education Table . This isLiving in close proximity to rivers and streams has previously been associated with increased risk for KSHV . We did Women attending routine ante-natal clinics are frequently used in surveys of HIV prevalence in South Africa and other African countries. Assessing KSHV prevalence in this population therefore allows for valid comparisons between this study and future studies in other parts of South Africa or other African countries. This study adds to findings in South Africa and other African countries  which suThe authors declare that they have no competing interestsBIM-K performed the statistical analysis, wrote the first draft of the manuscript and participated in the design of the study, PM and MM supervised the statistical analysis and contributed to the writing of the manuscript, GM performed the KSHV serology, FS conceived the study and with LS and ER, participated in the design of the study, the statistical analysis and contributed to the writing of the manuscript, DW participated in the design of the study, supervised the KSHV serology and contributed to the writing of the manuscript. All authors read and approved the final manuscript.


Sir,When older age groups were examined, some upward trends in breast cancer registrations were observed, particularly in young and middle-aged women in Vaud, but there was again no indication of a recent sudden rise. At ages 40–49 years, rates were 118.5 in 1995 and 184.9 in 2005, the rates were 307 and 338.2 at ages 50–69 years, 339.9 and 338.4 at ages 70–79 years, and 358.2 and 366.1 at ages 80 and above. Corresponding rates for Neuchâtel were 126.5 in 1995 and 186.4 in 2005 at age 40–49 years, 392.8 and 319.7 at age 50–69 years, 251.0 and 423.7 at age 70–79 years, and 374.4 and 422.5 at ages 80 years and above.These data from the Vaud and Neuchâtel Cancer Registries confirm therefore that breast cancer incidence registration has been rising over the last decade, particularly in young and middle-aged women. This rise is largely or totally due to increased detection. In fact, an organised mammography screening programme has been in operation in Vaud since 1999 for women aged 50–70 years .The present data do not confirm the existence of a substantial rise in breast cancer incidence in younger women in recent years. The upward trends in Geneva may therefore be due to the play of chance, since they were based only on 50 cases registered in 2003-2004, or the detection of prevalent cases due to increased use of mammography in young women in recent years.