bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evidence of thiazolidinedione‐induced improvement of pancreatic β‐cell function in patients with type 2 diabetes mellitus
Authors: Ovalle F. , Bell D. S. H.
Published: March 2003

Background: There is growing evidence in animal and in vitro studies showing that thiazolidinediones (TZDs) improve pancreatic beta cell (β‐cell) function. The aim of this study was to evaluate the effect of thiazolidinediones on the β‐cell function of patients with Type 2 diabetes mellitus (T2DM) in clinical practice.

Patients and Methods: This is an observational, nested case‐control study. We identified 28 patients (TZD group), with T2DM, who had had a meal‐stimulated C‐peptide level documented before the addition of troglitazone to a failing double‐therapy regimen with metformin (MET) and sulphonylurea (SU). As a control group (CTRL), we identified 26 patients, with T2DM, who also had had a meal‐stimulated C‐peptide documented before adding MET to a failing SU monotherapy regimen. We then proceeded to prospectively remeasure their meal‐stimulated C‐peptide levels and compared the changes over time between the two groups.

Results: Both groups were well matched for age, body mass index (BMI), and HgbA1c before and after treatment. The C‐peptide in the TZD group increased significantly during therapy (from 3.2 ± 0.5 to 4.2 ± 0.5, p = 0.01), whereas it remained unchanged in the CTRL group (from 4.8 ± 0.6 to 5.0 ± 0.5, p = 0.74). The C‐peptide/glucose ratio also increased significantly in the TZD group (from 1.9 ± 0.3 to 3.1 ± 0.3, p = 0.0003) whereas it remained unchanged in the CTRL group (from 3.4 ± 0.7 to 3.4 ± 0.3, p = 0.97). Furthermore, the C‐peptide/glucose ratio of the TZD group, which was significantly lower at baseline compared with the CTRL group (1.9 ± 0.3 vs. 3.4 ± 0.7, p = 0.04), caught up to its level during treatment (3.1 ± 0.3 vs. 3.4 ± 0.3, p = 0.48).

Conclusion: Thiazolidinediones seem to induce recovery of pancreatic beta cell function, independently of the correction of glucose toxicity.
Does insulin lispro preserve the physiological defences to hypoglycaemia during intensive insulin therapy with a conventional basal bolus regimen?
Authors: Heller S. R. , Amiel S. A. , Evans M. L. , Kong M.‐F. , Macdonald I. A. , Peacey S. R.
Published: March 2003

Aim: Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human‐soluble insulin but reduces rates of hypoglycaemia. We tested the hypothesis that the use of rapid‐acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy.

Methods: Ten patients with type 1 diabetes (four female, mean age 33 ± 3 years, diabetes duration 12 ± 2 years) participated in an open, randomized cross‐over study, with 2 months run‐in and 4‐month treatment periods using either lispro or human‐soluble insulin before meals and human NPH insulin (NPH) at night. The total of reported hypoglycaemic episodes (lispro vs. soluble, 123 vs. 128) and HbA1c (6.1 ± 0.2 vs. 6.6 ± 0.2%) were similar during both treatments. At the end of each period, we measured symptomatic, counterregulatory and cognitive responses, and glycaemic thresholds during hypoglycaemia, induced with a hyperinsulinaemic clamp (blood glucose of 5, 4.5, 3.5 and 2.5 mmol/l).

Results: We found similar overall responses of adrenaline, cortisol, growth hormone and total symptom score. Glycaemic thresholds for rises in adrenaline (3.1 ± 0.2 vs. 3.1 ± 0.2 mmol/l, p = 0.76), cortisol (2.2 ± 0.1 vs. 2.2 ± 0.1 mmol/l, p = 0.16), growth hormone (3.3 ± 0.15 vs. 2.9 ± 0.2 mmol/l, p = 0.13), symptoms (3.2 ± 0.2 vs. 3.3 ± 0.1 mmol/l, p = 0.051) and impaired cognitive function (3.0 ± 0.2 vs. 3.0 ±0.2 mmol/l, p = 0.20) were also similar.

Conclusion: Four months of intensive treatment, with insulin lispro used pre‐prandially and isophane at night, produced relatively preserved but equivalent physiological responses to hypoglycaemia as those on soluble insulin. Longer periods of treatment or alternative regimens may be necessary to demonstrate beneficial effects on hypoglycaemic physiological responses.
Serum homocysteine concentration is related to diabetes mellitus, but not to coronary heart disease, in Saudi Arabians
Authors: Al‐Nozah M. , Al‐Daghri N. , Bartlett W. A. , Al‐Attas O. , Al‐Maatouq M. , Martin S. C. , Kumar S. , Jones A. F.
Published: March 2003

Introduction: Plasma homocysteine (HCYS) concentration is believed to be an independent risk factor for atherosclerosis.

Methods: HCYS was measured in a cohort of 584 Saudi Arabians participating in a national screening study of coronary heart disease (CHD) risk factors. A total of 173 subjects (114 men and 59 women) had clinical CHD, of whom 82 (47.4%) had type 2 diabetes mellitus (56 men and 26 women). A further 127 subjects (60 men and 67 women) also had type 2 diabetes mellitus but no CHD. A total of 284 individuals (120 men and 164 women) were recruited as healthy controls, and had no previous history of CHD or diabetes. Serum HCYS was measured by high‐performance liquid chromatography (HPLC) with electrochemical detection.

Results: Univariate analysis showed HCYS concentrations were significantly lower in those with diabetes mellitus (DM) than in controls, for both men [8.7 (4.2–18.6) vs. 10.5 (4.5–20.5) mmol/l, median (5th−95th percentiles, p = 0.009] and women [6.3 (3.3–24.0) vs. 8.1 (4.0–17.9) mmol/l, p = 0.049]. Stepwise multivariate regression analysis indicated a relationship between HCYS concentration and age, sex and the presence of DM, but not with CHD.

Conclusions: In the Saudi Arabian population, serum HCYS is not a risk factor for CHD, but is lower in patients with DM.
Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia
Authors: Whitelaw D. C. , Smith J. M. , Nattrass M.
Published: March 2003

Aim: To examine whether lowering of plasma triglyceride concentrations using the fibrate peroxisome proliferator‐activated receptor (PPAR)α agonist gemfibrozil would influence insulin sensitivity to various aspects of intermediary metabolism among subjects with type 2 diabetes mellitus.

Methods: A randomized placebo‐controlled double‐blind study in 12 subjects with type 2 diabetes were treated for 12 weeks after a 12‐week dietary run‐in. Insulin sensitivity was assessed using a low‐dose incremental intravenous insulin infusion.

Results: Gemfibrozil significantly reduced fasting serum triglyceride concentrations (p < 0.001) but had no effect on measures of diabetic control. Neither gemfibrozil nor placebo treatment altered insulin sensitivity of glucose or glycerol metabolism during low‐dose insulin infusion, but significant falls in both non‐esterified fatty acid (NEFA) (p = 0.003) and ketone concentrations (p = 0.002) were observed after treatment with gemfibrozil.

Conclusions: Gemfibrozil does not affect insulin sensitivity to glucose or fat metabolism in type 2 diabetes but enhances the lowering of plasma NEFA concentrations by insulin, probably by reducing hepatic fatty acid synthesis.
Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes
Authors: Pan J. , Lin M. , Kesala R. L. , Van J. , Charles M. A.
Published: March 2003

Objective: We tested the hypotheses that niacin is effective for the separate treatments of abnormalities of LDL particle size, HDL2 percentage and Lp(a) without potential negative effects on glycated haemoglobin.

Research Design and Methods: The atherogenic lipid profile lipids, such as triglycerides, small, dense LDL cholesterol (LDLc) particle mass, LDL particle size, total HDLc and HDL2 percentage as well as Lp(a), were measured in 42 diabetic patients with abnormalities of LDL particle size, HDL2 percentage and/or Lp(a) levels before and after niacin treatment. LDL particle size and HDL2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was measured by enzyme‐linked immunoabsorbance assay (ELISA).

Results: After niacin treatment, LDL peak particle diameter increased from 252 ± 7 Å to 263 ± 7 (p < 0.0001), small, dense LDLc particle mass decreased from 27 ± 11 mg/dL to 15 ± 4 (p < 0.0001), total HDLc increased from 39 ± 7 mg/dL to 51 ± 11 (p < 0.0001), HDL2 as the percentage of total HDLc mass increased from 29 ± 8% to 45 ± 10 (p < 0.0001) and Lp(a) decreased from 43 ± 17 mg/dL to 25 ± 10 (p < 0.0001). Mean haemoglobin A1c level was improved during treatment from 7.6 ± 1.8% to 6.5 ± 1.0 (p < 0.0001) using increased oral agent and insulin treatment doses in more than 90% of the patients. A total of 21% of the patients were unable to tolerate niacin owing to reversible side‐effects, and 14% were unable to adhere to the niacin dosing regimen of three times daily.

Conclusions: These data indicate that in diabetic patients, niacin (i) is effective for treating diabetic dyslipidaemias associated with both the atherogenic lipid profile and Lp(a); (ii) must be used with modern and aggressive oral hypoglycaemic agents or insulin treatment; and (iii) is an important drug to treat diabetes dyslipidaemias because of its broad spectrum of effectiveness.
Changes in risk factors for cardiovascular disease with body fat loss in obese women
Authors: Krebs J. D. , Evans S. , Cooney L. , Mishra G. D. , Fruhbeck G. , Finer N. , Jebb S. A.
Published: March 2003

Background: Current guidelines for obesity management emphasize the improvements in health risks associated with weight losses of 5–10% initial weight. However, most of the data is derived from periods of acute weight loss and may not represent the true effect in the longer term or in obese but otherwise healthy individuals. This study examines the temporal changes in risk factors for cardiovascular disease with weight change over 52 weeks.

Methods: In total, 57 overweight women (age 43.7 ± 9.1 years, mean BMI of 31.7 kg/m2, range 27.2–38.5 kg/m2) with no other significant medical history, entered a milk‐based, low‐energy weight loss programme for 12 weeks and were then monitored without further intervention until 52 weeks. Weight, fat mass, fasting plasma insulin, lipids and blood pressure were measured at 0, 12, 24 and 52 weeks.

Results: The mean weight change in sequential periods was −11.6% (p < 0.0001), +1.1% (p = 0.02) and +5.2% (p < 0.0001). The change from baseline to 1 year being −6.0% (p < 0.0001) an 11% (p < 0.0001) reduction in initial body fat mass. Initial weight loss (0–12 weeks) was positively correlated with greater longer term weight loss (0–52 weeks, r = 0.75, p < 0.0001) and not with weight regain (12–52 weeks, r = 0.14, p = 0.28). Despite significant improvements in insulin sensitivity, lipid profile and blood pressure (BP) with acute weight loss, in the group overall, only benefits in BP were maintained after 52 weeks. However, improvements in insulin sensitivity were sustained in those who maintained more than 5% weight loss, and those with higher baseline metabolic risk had greater benefits with weight loss. Change in waist circumference was better than BMI or fat mass in predicting improvements in metabolic risk in these obese women.

Conclusions: This study suggests, in otherwise apparently healthy obese women, the rationale of targeting individuals most likely to benefit from weight management. Most importantly it highlights the need to focus on achieving initial weight losses of greater than 10% to maintain longer term losses of at least 5% and the associated health benefits.
Treating peripheral arterial disease in patients with diabetes
Authors: Hittel Norbert , Donnelly Richard
Published: March 2003

Diabetes is associated with considerably higher risks of developing peripheral arterial disease (PAD) which, when it occurs, is more severe and progresses more rapidly than in nondiabetics. Early detection of PAD in the diabetic patient is therefore important, but may be complicated by the presence of neuropathy and calcification of the arteries such that ischaemic symptoms are not felt by the patient and ankle pressures are not reduced. Toe pressures are an alternative diagnostic tool in these patients. Good glycaemic control, while an essential part of diabetes management, does not appear to bring more than modest benefits in preventing the peripheral vascular complications of diabetes. Therefore, attention to other risk factors is needed. Treatment with the phosphodiesterase III inhibitor, cilostazol, has been shown to improve walking distances significantly in diabetes patients with intermittent claudication and also appears to improve plasma lipid profiles. Further, cilostazol has an antiplatelet action, which may prove to be of benefit in diabetes because hyperglycaemia is associated with increased platelet aggregability. Revascularization in diabetes patients with critical leg ischaemia is complex and associated with poorer outcomes than in non‐diabetes patients. While surgical revascularization has better patency rates, in patients at high risk of surgical complications, percutaneous transluminal angioplasty may be a better option.
Fine structure and development of the cuticle of Intoshia variabili (Orthonectida)
Authors: Slyusarev George S.
Published: March 2003

The body of free‐swiming mature Intoshia variabili (Orthonectida) is covered by a thin cuticle, 0.3 μm thick. The cuticle is formed at the time when the orthonectid embryos develop in the plasmodium. The process of cuticle formation begins just after the first cilia begin to appear at the surface of the ciliated cells. At first, small extensions of the cell membrane appear at the surface of the cell, more or less parallel to the cell surface. As they develop futher, they stand up, and amorphic material begins to appear between them. The extensions then become microvilli and obtain their final shape, with a small subdistal swelling and a narrower distal part. They are situated very regularly on the surface of the cell. After the microvilli have obtained their final form, material between them begins to get its final structure typical of the adult form. During the period when the mature orthonectid begins to leave the plasmodium and emerge from the host, the regular microvilli begin to disappear, and only small irregular extensions are present under the cuticle on the surface of the cell. During the process of cuticle formation a large amount of smooth endoplasmic reticulum develops in the cells, but once the cuticle is formed it gradually disappears.
An SEM study of the jaws of Haplognathia rosea and Rastrognathia macrostoma (Gnathostomulida), with a preliminary comparison with the rotiferan trophi
Authors: Sørensen Martin V.
Published: March 2003

The preparation of gnathostomulid jaws for scanning electron microscopy is demonstrated, and descriptions of the jaws from Haplognathia rosea and Rastrognathia macrostoma are given. These jaws represent two different gnathostomulid jaw types, namely the ‘compact type’ and the ‘basket type’. The described structures are compared with sclerites in the rotifer trophi, and some homologies are suggested. The observations support a close relationship between Gnathostomulida and Rotifera.
Orbital rete and red muscle vein anatomy indicate a high degree of endothermy in the brain and eye of the salmon shark
Authors: Tubbesing Victor A. , Block Barbara A.
Published: March 2003

The salmon shark has been ranked as the most endothermic lamnid shark based upon geographical range, extent of slow twitch muscle, supra‐hepatic rete size, and limited temperature measurements, yet its anatomy has remained largely undescribed, and measurements of brain or eye temperatures have not been reported. In this study, four specimens are examined to determine if the morphological requirements for warming the brain and eyes are present. A well‐developed arterial orbital rete lies within a venous sinus on both sides of the cranium. Cool, oxygenated blood from the gills can pass through the vessels of this exchanger before reaching the brain or eyes. Since venous blood in the sinus flows opposite the arterial blood, counter‐current heat exchange can occur. A vein originating in the red swimming muscle likely contributes to the warmth of the venous sinus by supplying blood directly from the warmest region of the shark. Before collecting in the orbital sinus, this red muscle vein bathes the brain in warm blood. These morphological data suggest the salmon shark has a significant capacity to warm the brain and eyes.
Outer retinal fine structure of the garfish Belone belone (L.) (Belonidae, Teleostei) during light and dark adaptation – photoreceptors, cone patterns and densities
Authors: Reckel Frank , Melzer Roland R. , Smola Ulrich
Published: March 2003

In the present EM study, we investigate the retina of Belone belone, a visually‐orientated marine predator living close to the water surface. In the duplex retina, four morphologically different cone types are observed: unequal and equal double cones, long single cones and triple cones. In the light‐adapted state, five different cone patterns occur: row, twisted row, square, pentagonal and hexagonal patterns. High double cone densities are found ventro‐nasally, ventro‐temporally and dorso‐temporally. Throughout the retina the double cone/single cone ratio is 2 : 1, in the ventral part, however, a 1 : 1 ratio occurs. In the vitreous body we found a curtain‐like intraocular septum dividing the retina into two morphologically different regions. In most areas of the dark‐adapted retina the cone patterns are absent at the ellipsoid level, with long single cones standing more vitreally in the light path than double cones. The mosaics are retained, however, in the outer nuclear layer. Typical dark adaptation, i.e. the retinomotor movements of the retinal pigment epithelium and photoreceptors in response to the dark adaptation (light change) is not present in the peripheral ventral and parts of the central ventral area. In both regions we found a twisted row pattern of cones having a vitreal position. The findings are discussed with respect to the photic habitat and feeding habits of this species.
Epidermal receptor development and sensory pathways in vitally stained amphioxus (Branchiostoma floridae)
Authors: Holland Nicholas D. , Yu Jr‐Kai
Published: March 2003

Chloromethyl (CM) DiI was applied to the exterior of living embryos, larvae, and metamorphic juveniles of amphioxus. This fluorescent dye is taken up preferentially (but not highly selectively) by epidermal receptors and often stains sensory axons to their full extent. Type I primary receptors in the epidermis first become morphologically detectable along the rostrocaudal axis of the 2.5 day larva when their epidermal perikarya extend unbranched axons to the nerve cord. These axons run posteriorly or anteriorly within the nerve cord, depending on whether their perikarya are located, respectively, rostral or caudal to the most posterior pharyngeal slit. In later larvae, axons of type I receptors are organized into a dorsal and a subdorsal sensory tract on either side of the nerve cord. In the epidermis of metamorphic juveniles, CM‐DiI also stains type II receptors (which are axonless, secondary receptors) and ventral pit cells (which may not be receptors). It is probable, but not yet conclusively demonstrated, that peripheral neurites from Retzius bipolar cells (primary intramedullary sensory neurones) synapse with type II secondary epidermal receptors or ramify freely among the other epidermal cells. The discussion considers homologies among epidermal sensory receptors in chordates.
The lateral line canal sensory organs of the Epaulette Shark (Hemiscyllium ocellatum)
Authors: Jørgensen Jørgen Mørup , Pickles James O.
Published: March 2003

Examination of the lateral line canals in the Epaulette Shark reveals a much more differentiated sensory system than previously reported from any elasmobranch. Two main types of lateral line canals are found. In one type rounded patches of sensory epithelia are separated by elevations of the canal floor. The other type is a straight canal without restrictions and with an almost continuous sensory epithelium. In addition, we found epithelia (type A) with very long apical microvilli on the supporting cells. These microvilli reach beyond the stereovilli of the hair cells. Another type (B) of sensory epithelium has short microvilli on the supporting cells. In this latter type of epithelium the stereovilli of the hair cells are comparatively tall and reach out beyond the supporting cell microvilli.

 New hair cells are found widely in both types of sensory epithelia. These always occur as single cells, unlike those described in teleost lateral line canal sensory epithelia where new hair cells seem to form in pairs. Dying hair cells are also widespread, indicating a continuous turnover of hair cells.
An investigation of erectile dysfunction in Gwent, Wales
Authors: Green J.S.A. , Holden S.T.R. , Ingram P. , Bose P. , St George D.P. , Bowsher W.G.
Published: March 2003

Objective To quantify incidence of erectile dysfunction (ED) and the associated risk factors in men attending community clinics in a large population in Wales, UK.

Subjects and methods Of 4060 men who were invited to attend 11 community clinics, primarily to check for prostate disease, 2025 (aged 55–70 years) attended. Of these, 2002 men answered a questionnaire about personal details, medical, family and sexual history, and detailed alcohol and smoking habits. All had their serum prostate‐specific antigen (PSA) analysed and those referred for investigation of prostatic disease underwent serum testosterone analysis.

Results Complete ED was reported by 265 men (13.2%), and was closely related to age (r = 0.19, P < 0.001) and medication (r = 0.2, P < 0.001). ED occurred in 6.9% of men aged 55–60 years, 12.5% aged 61–65 and 22.2% of those aged 66–70. Patients taking diabetic medication had the highest relative risk for ED and 11.3% of men with ED were taking nitrates. The numbers of years of smoking had the third closest correlation with impotence (r = 0.16, P < 0.001). A low serum testosterone level was a poor predictor of ED and increasing serum PSA levels did not influence the distribution of ED.

Conclusion About 13% of these men aged 55–70 years had complete ED; if this value is extrapolated to the whole of the UK, this equates to almost half a million men being unable to achieve any erections. The estimate would be much greater if those with milder forms of ED are included.
Efficacy and safety of tolterodine in patients with detrusor instability: a dose‐ranging study
Authors: Rentzhog  , Stanton  , Cardozo  , Nelson  , Fall  , Abrams
Published: March 2003

Objective

 To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence).

Patients and methods

 A double‐blind, placebo‐controlled, multicentre study was carried out; after a 1‐week run‐in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks’ treatment.

Results

 A per‐protocol analysis of efficacy in 64 patients showed dose‐related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of≤2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings.

Conclusion

 The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1–2 mg twice daily.
Piroxicam fast‐dissolving dosage form vs diclofenac sodium
Authors: SupervÍa  , Pedro‐Botet  , NoguÉs  , Echarte  , Mínguez  , Iglesias  , Gelabert
Published: March 2003

Objective

 To assess the possible therapeutic effect of 40 mg sublingual piroxicam (fast‐dissolving dosage form, FDDF) compared with intramuscular 75 mg diclofenac, as a reference drug, on acute renal colic in a randomized, double‐blind controlled clinical trial.

Patients and methods

 Eighty patients were assigned to one of two treatment groups; one received an intramuscular injection with 0.2 mL distilled water and two sublingual tablets of 20 mg piroxicam FDDF, and the other received an intramuscular injection with 75 mg diclofenac sodium and two sublingual tablets of placebo. Pain intensity was evaluated by the patient using a visual analogue scale and by the observers. Vital signs at baseline and 30 min after the administration of the study drugs were also recorded.

Results

 The overall efficacy of the treatment was 81%; nine patients in the piroxicam and six in the diclofenac group (no significant difference) required rescue treatment. Compared with baseline levels, the pain relief was significant (P<0.001) at 30 min in both groups. Twenty‐two patients in the piroxicam and 25 in the diclofenac group attained complete pain relief at 30 min, as evaluated by the observer (no significant difference). Both treatments were similarly effective in decreasing vital signs, mainly systolic blood pressure, heart and respiratory rates. However, when the percentage change was compared between the groups, piroxicam significantly decreased the respiratory rate (P<0.03).

Conclusion

 Piroxicam FDDF is as effective as parenteral diclofenac in emergency renal colic treatment. Furthermore, its ease of self‐administration increases patient compliance and potential use in general practice.
Modified ureterosigmoidostomy (Mainz II) — technique and early results
Authors: Woodhouse  , Christofides
Published: March 2003

Objective

 To assess the surgical method and results at 3 months of ureterosigmoidostomy modified by reconfiguration of the rectum to make a low‐pressure reservoir.

Patients and methods

 Over the last 8 years, patients undergoing lower urinary tract reconstruction have been followed using a written protocol; the data from patients undergoing a modified ureterosigmoidostomy were retrieved for a retrospective analysis. Two groups of patients were defined: in group A, 15 patients underwent cystectomy and diversion by modified ureterosigmoidostomy and in group B, four patients already had a conventional ureterosigmoidostomy which was incontinent, and the rectum was reconfigured to improve control. The incidence of complications and causes of incontinence were assessed.

Results

 The rectum was reconfigured by longitudinal incision and transverse closure in a ‘U’ fashion (Mainz II) in 17 patients, and augmented with ileum in two. There were no surgical complications. In group A all patients were continent at 3 months and in group B only two of four were continent; one patient in group A subsequently became incontinent. All incontinence was caused by chronic retention and overflow. There were no cases of pyelonephritis during follow‐up to 29 months and no ureteric reflux was detected.

Conclusions

 Modified ureterosigmoidostomy is a safe method of urinary diversion after cystectomy. A longer follow‐up is needed to judge its place compared with other forms of diversion. It has a limited place in the management of incontinence in those with a long‐standing conventional ureterosigmoidostomy.
The role of power Doppler ultrasonography in the diagnosis of acute pyelonephritis
Authors: Sakarya  , Arslan  , Erkoç  , Bozkurt  , Atilla
Published: March 2003

Objective

 To assess the ability of power Doppler ultrasonography (PDU) to detect acute pyelonephritis and to compare the findings from PDU with those from enhanced computed tomography (CT).

Patients and methods

 Eleven patients (mean age 18.5 years, range 5–37) admitted to hospital with a clinical diagnosis of pyelonephritis were assessed with PDU and enhanced CT, the latter providing the reference method.

Results

 The imaging studies showed normal findings in three patients; a single focus of pyelonephritis was detected by CT in six, whereas a matching defect was detected on PDU in five, with PDU failing to detect an infective focus in one. Multifocal diffuse pyelonephritis was diagnosed correctly by enhanced CT and PDU in two patients.

Conclusion

 Power Doppler ultrasonography had an overall sensitivity of 88% and complete specificity in the evaluation of patients with acute pyelonephritis.
Transurethral resection of the prostate in the
Authors: Chakravarti  , Macdermott
Published: March 2003

Objective

 To assess the safety of transurethral prostatectomy (TURP) in patients on long‐term full anticoagulation.

Patients and methods

 Twelve TURPs were performed on 11 patients with urinary retention or severe symptoms from prostatic obstruction who also required anticoagulation for a history of life‐threatening thrombo‐embolic disease (seven) or prosthetic heart valves (four). Patients stopped taking warfarin 3 days before surgery; on admission a day later, full intravenous heparinization was commenced. Heparin was stopped 4 h before TURP and re‐commenced with an initial bolus in the recovery room, and warfarin re‐started that evening.

Results

 The mean weight of prostate resected was 23 g and the mean peri‐operative decrease in haemoglobin was 1.6 g/dL. Only one patient required a transfusion of 3 units, but the activated partial thromboplastin time (APTT) had risen to >4. The mean pre‐ and post‐operative APTT were 1.7 and 2.64, respectively, and the mean total length of hospital stay 6.7 days. Three patients were re‐admitted for secondary haemorrhage at 8, 9 and 28 days after TURP, but all resolved with catheterization for 24 h only. There were no other major complications or thrombo‐embolic phenomena.

Conclusion

 TURP can be conducted safely in this high‐risk group of patients with a regimen that allows a brief but controlled interruption to their full anticoagulation. This protects from the risks of thrombo‐embolic incidents with no major increase in haemorrhage or hospital stay.
The results of holmium laser resection of the prostate
Authors: Mackey  , Chilton  , Gilling  , Fraundorfer  , Cresswell
Published: March 2003

Objective

 To assess the results of holmium–laser resection of the prostate (HOLRP) in the treatment of benign prostatic hyperplasia.

Patients and methods

 Between 1994 and 1997, 967 patients underwent HOLRP in Tauranga, New Zealand, and in Derby, United Kingdom. The patients were followed at 1, 3 and 6 months after treatment using measurements of symptom score and urinary flow rate.

Results

 There was a large and sustained improvement in symptom scores and urinary flow rates, with no mortality and low morbidity.

Conclusion

 We recommend this technique as an alternative to transurethral resection in the surgical treatment of bladder outlet obstruction due to benign prostatic hypertrophy.
The value of prostate specific antigen (PSA) density and free: total PSA ratio in selecting patients with a normal digital rectal examination and intermediate total PSA levels for further investigation
Authors: Klingler  , Woo  , Rosario  , Cutinha  , Anderson  , Ward  , Chapple
Published: March 2003

Objectives

 To examine the use of prostate‐specific antigen (PSA) density (PSAD) and free to total PSA ratio (f/tPSA) in enhancing the specificity of PSA in the diagnosis of prostate cancer in patients with a total PSA (tPSA) of 4–10 ng/mL and with a normal digital rectal examination (DRE).

Patients and methods

 The study comprised 77 consecutive men in whom the fPSA and tPSA levels were obtained before DRE and transrectal ultrasonography‐guided sextant prostate biopsy. Prostate cancer was found in 39 patients and the histology was benign in 38. Receiver operator characteristic curves, obtained from all 77 patients, were used to determine the optimal thresholds for PSAD and f/tPSA in detecting cancer. A subset of 28 patients, including seven with prostate cancer, was identified who had a normal DRE and a tPSA of 4–10 ng/mL; PSAD and f/tPSA values were applied at the optimal thresholds to assess their use in identifying those patients with cancer.

Results

 When applied to the selected group of 28 patients, the PSAD (threshold 0.15) failed to identify any with prostate cancer. The f/tPSA (threshold 0.12) yielded a sensitivity of 65% and a specificity of 38%, identifying only three of seven patients with cancer. By increasing the threshold to 0.25, six patients were correctly identified, giving a sensitivity of 86%, with a lower specificity of 14%.

Conclusions

 These findings suggest that the neither PSAD nor f/tPSA either significantly reduce the negative biopsy rate or identify patients at greater risk of prostate cancer, particularly when the tPSA is equivocal at 4–10 ng/mL.
Urodynamic variables cannot be used to classify the severity of detrusor instability
Authors: Wagg  , Bayliss  , Ingham  , Arnold  , Malone‐Lee
Published: March 2003

Objective

 To explore the relationship between subjective severity of symptoms of detrusor instability (DI) on presentation, outcome after treatment for DI and initial diagnostic urodynamic variables, with the aim of identifying a urodynamic variable which might, by predicting a favourable outcome from treatment, classify the severity of DI.

Patients and methods

 Women with a urodynamically proven diagnosis of DI were recruited prospectively for the study. Data on disease symptoms and variables from their diagnostic cystometrogram were collected. All women were then treated and their outcome at 6 weeks after treatment compared with the initial urodynamic variables. Data on severity of symptoms were compared with initial urodynamic variables to explore any differences in these variables attributable to symptom severity.

Results

 Of 300 women studied (mean age 54 years, sd 16), 290 were treated with oxybutynin and bladder retraining. At 6 weeks, 82 women had their treatment outcome classified as worse/no change; 218 women had improved. When good or poor outcome was compared with the urodynamic results, there was no significant difference between the groups. Likewise, the severity of symptoms did not relate to the values of urodynamic variables.

Conclusions

 There was no statistically significant relationship between reported severity of symptoms and urodynamic variables, and no relationship between the urodynamic variables used and response to treatment. Therefore, using these values it is not possible to predict a favourable outcome from treatment or to use them to classify disease severity.
A morphometric and ultrastructural study of the changes in the lamina propria in adolescents with varicocele
Authors: Santoro  , Romeo  , Impellizzeri  , Arco  , Rizzo  , Gentile
Published: March 2003

Objective

To verify if changes in the lamina propria and its components, reported in adults with varicocele, are already present in adolescents with idiopathic varicocele, using a morphometric and ultrastructural study.

Materials and methods

Twenty testicular biopsies from adolescents (mean age 15.6 years) were obtained during surgery for left idiopathic varicocele; five testicular biopsies from adolescents (mean age 16 years) undergoing surgery for hydrocele or inguinal hernia were used as controls. Biopsy specimens were processed for light and transmission electron microscopy; the sections were evaluated morphometrically using computerized image analysis.

Results

Morphometric and ultrastructural examination of the testes with varicocele showed an increased thickness in the lamina propria, caused principally by an increase in the extracellular matrix components, and deep invaginations towards the germinal epithelium.

Conclusion

There is detectable damage of the lamina propria in adolescents affected by left idiopathic varicocele, although not as well developed or as severe as in adults.
β‐sitosterol for the treatment of benign prostatic hyperplasia:
Authors: Wilt  , Macdonald  , Ishani
Published: March 2003

Objectives

To conduct a systematic review of the evidence for the efficacy of β‐sitosterolin men with symptomatic benign prostatic hyperplasia (BPH).

Methods

Studies were identified through Medline™ (1966–98), EMBASE™ , Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with study authors and pharmaceutical companies. Randomized trials were included if: men had symptomatic BPH; plant extract preparations contained β‐sitosterols; a control group received placebo or a pharmacological therapy; and treatment duration was ≥30 days. Study characteristics, demographic information, enrolment criteria and outcomes were extracted.

Results

Four trials comprising a total of 519 men met the inclusion criteria. All were double‐blind and lasted 4–26 weeks. Three studies used nonglucosidic β‐sitosterols and one used a preparation that contained only β‐sitosterol‐β‐d‐glucoside. Compared with placebo, β‐sitosterolimproved urinary symptom scores and flow measures. For the two studies reporting the International Prostate Symptom Score (IPSS), the weighted mean difference (WMD) against placebo was −4.9 IPSS points (95% confidence interval, CI,−6.3 to−3.5). The WMD for peak urinary flow rate was 3.91 mL/s (95% CI 0.91 to 6.90, four studies) and for residual volume the WMD was −28.62 mL (95% CI−41.42 to−15.83, four studies). β‐sitosteroldid not reduce prostate size. The trial using pure β‐sitosterol‐β‐d‐glucoside (WA184) showed no improvement in urinary flow measures. Withdrawal rates for men assigned to β‐sitosterol and placebo were 7.8% and 8.0% (not significant), respectively.

Conclusion

β‐sitosterolimproves urological symptoms and flow measures. However, the existing studies are limited by short treatment duration and lack of standardized β‐sitosterol preparations. Their long‐term effectiveness, safety and ability to prevent the complications of BPH are unknown.
Free prostate‐specific antigen ‘in the field’: a useful adjunct to standard clinical practice
Authors: Collins  , Alexandrou  , Wynn‐Davies  , Mobley  , O’Reilly
Published: March 2003

Objectives

To determine the clinical utility of the ratio of free to total prostate‐specific antigen (f/tPSA), which may improve the discrimination of PSA testing in the assessment of patients with prostatic disease, in a busy clinical practice.

Patients and methods

A series of 198 men undergoing transrectal ultrasonography (TRUS)‐guided biopsy, because of a high total PSA level or an abnormal digital rectal examination or both, had blood samples taken for the assessment of both free and total PSA before any form of prostatic manipulation. The histological findings were compared with tPSA, fPSA and f/tPSA, evaluating three different thresholds of f/tPSA.

Results

PSA levels, PSA density and fPSA density differed significantly between those with benign histology and neoplasia. The f/tPSA only differed significantly in men with a PSA level of 10.1–15 ng/mL. The f/tPSA threshold of 0.25 was the most useful clinically, with a negative predictive value for prostate cancer of 91%. Using this threshold would reduce the negative biopsy rate by 30%.

Conclusion

The f/tPSA is of clinical value in reducing the negative biopsy rate and in the management of patients with a high PSA level and previous negative biopsies.
Carbachol‐induced sustained tonic contraction of rat detrusor muscle
Authors: Oh  , Ahn  , Kim  , Kim  , Lee  , Kim  , Choi
Published: March 2003

Objective

To investigate the underlying contractile mechanism of the sustained tonic contraction (SuTC) induced by repetitive carbachol application in rat detrusor muscles.

Materials and methods

Longitudinal muscle strips with no mucosa were obtained from the anterior wall of the urinary bladder in 12‐week‐old Sprague–Dawley rats. Carbachol (5 μmol/L) was applied repetitively to induce SuTC. The carbachol‐induced SuTC was assessed in the presence of various Ca2+‐channel blockers and drugs affecting intracellular Ca2+ concentration.

Results

The first application of carbachol elicited a large phasic contraction followed by a tonic contraction (TC); the carbachol‐induced contraction was completely reversed by washing out the solution. However, the initial phasic contraction was not reproduced after a second or further application of carbachol. There was consistently only a SuTC with no phasic contraction. The amplitude of the SuTC was 85% of the TC induced by the first carbachol application. The application of atropine (1 μmol/L) to the bath completely blocked SuTC. The carbachol‐induced SuTC was insensitive to nicardipine (5 μmol/L) and extracellular polyvalent cations (1 mmol/L, La3+ , Co2+ , Cd2+ , Ni2+ ). Moreover, a similar SuTC was induced even after the complete elimination of extracellular Ca2+ by adding 2 mmol/L EGTA to the Ca2+‐free Tyrode solution. To exclude intracellular Ca2+ sources related to the sarcoplasmic reticulum (SR), the effects of SR Ca2+ pump inhibitors, cyclopiazonic acid (CPA, 10 μmol/L) and thapsigargin (0.5 μmol/L) were tested. The carbachol‐induced SuTC was insensitive to pretreatment with CPA and/or thapsigargin. To deplete the ryanodine‐sensitive Ca2+ pool, muscle strips were repetitively stimulated with caffeine (10 mmol/L) in the presence of 10 μmol/L ryanodine, which did not affect the carbachol‐induced SuTC.

Conclusions

Although the characteristics of the carbachol‐induced SuTC have not been defined, these results show that a significant proportion of the carbachol‐induced contraction in rats is contributed by the SuTC, which is present even in the complete absence of external Ca2+ . The SuTC was not affected by limiting the contributions of internal Ca2+ sources. This suggests that the SuTC in rat bladders is unrelated to known Ca2+ mobilization mechanisms.
The incidence of phimosis in boys
Authors: Shankar  , Rickwood
Published: March 2003

Objective

To establish the incidence of pathological phimosis in boys.

Patients and methods

A 2‐year review of circumcisions was performed for phimosis among a known population of boys, with the histological findings of the circumcision specimens assessed.

Results

Sixty‐two boys (all but one aged 5–14 years) had typical pathological (cicatrizing) phimosis and among the 51 circumcision specimens examined histologically, 43 (84%) showed appearances of balanitis xerotica obliterans. During the same period, 30 boys were circumcised for developmental unretractability of the foreskin (‘physiological phimosis’).

Conclusions

The incidence of pathological phimosis in boys was 0.4 cases/1000 boys per year, or 0.6% of boys affected by their 15th birthday, a value lower than previous estimates and exceeded more than eight‐fold by the proportion of English boys currently circumcised for ‘phimosis’.
Antenatally detected pelvi‐ureteric junction obstruction: concerns about conservative management
Authors: Subramaniam  , Kouriefs  , Dickson
Published: March 2003

Objective

To review the conservative management of antenatally detected pelvi‐ureteric junction (PUJ) obstruction in children.

Patients and methods

The study included 121 children (142 kidneys) with antenatally diagnosed PUJ obstruction managed over an 8‐year period, including 21 who were affected bilaterally; the main focus of the study was on the 100 children affected unilaterally. The intent was to manage these patients conservatively, with immediate surgery (early pyeloplasty) only if renal function was initially compromised (renographic function < 40%). The indications for surgery subsequently (delayed pyeloplasty) included either a deterioration in renal function, the onset of symptoms or increasing hydronephrosis.

Results

The anteroposterior diameter and renal function were weakly and negatively correlated. The kidneys in the delayed pyeloplasty group had a greater initial mean anteroposterior diameter than had those in the early or the conservative groups (P<0.05). The improvement in renal function was the lower in the delayed pyeloplasty group than in the early pyeloplasty group; the improvement was inversely related to the anteroposterior diameter.

Conclusions

The conservative management of some antenatally detected PUJ obstructions probably results in greater loss of function, which is not recovered after surgery.
The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: new risk factors for angiopathic erectile dysfunction?
Authors: Khan  , Thompson  , Emsley  , Mumtaz  , Mikhailidis  , Angelini  , Morgan  , Jeremy
Published: March 2003

Objectives

 To explore whether homocysteine (HCy), an independent risk factor for atherosclerosis (the angiopathic effect of which occurs through the generation of superoxide anions and hydrogen peroxide, augmented by copper, the superoxide anions reacting with nitric oxide, NO, to produce peroxynitrite, a highly angiopathic free radical) and copper contribute to erectile dysfunction (ED) through similar mechanisms, by assessing their interactive effects on the relaxation of corpus cavernosum using organ‐bath techniques.

Materials and methods

 Cavernosal smooth muscle strips were obtained from adult New Zealand White rabbits and mounted in organ baths. After precontraction with phenylephrine (100 μmol/L), relaxation responses to carbachol or sodium nitroprusside (SNP) were assessed in the presence or absence of HCy and copper. The effects of HCy and copper in the presence of superoxide dismutase or catalase were also investigated.

Results

 HCy alone inhibited carbachol‐stimulated (NO‐dependent) but not SNP‐stimulated relaxations (NO‐independent). This effect of HCy was significantly augmented by copper, which alone had no effect. The combined effect of HCy and copper was significantly (P<0.05) reversed by superoxide dismutase or catalase.

Conclusions

 HCy inhibited NO‐mediated cavernosal smooth muscle relaxation, an effect that was potentiated by copper and reversed by superoxide dismutase or catalase. It is therefore proposed that the effect of HCy on cavernosal smooth muscle relaxation is mediated by an interaction between NO and superoxide anions. Moreover, HCy may constitute a new risk factor for angiopathic ED.
Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer?
Authors: Sriplakich  , Jahnson  , Karlsson
Published: March 2003

Objective

To determine whether epidermal growth factor receptor (EGFR) immunostaining of tumour cells is associated with cancer‐specific death after cystectomy for locally advanced bladder cancer.

Patients and methods

The hospital records of all patients treated with cystectomy for urothelial cancer of the urinary bladder between 1967 and 1992 were reviewed retrospectively. The paraffin‐embedded specimens obtained before treatment from 173 patients were processed for immunohistochemical staining, using the monoclonal antibody NCL‐EGFR (Novocastra, UK). EGFR immunostaining was considered positive if membrane staining was found in at ≥20% of tumour cells in one or more fields at ≥200 (area 0.59 mm2 ).

Results

Most patients (149) received preoperative irradiation and one had neoadjuvant chemotherapy. The mean observation time was 81.3 months; 63 patients (36%) had tumour recurrence within 1–80 months (mean 18.3). Positive EGFR immunostaining was found in 100 patients (58%). The proportion of T2–4 tumours was higher in those EGFR‐positive than in those EGFR‐negative. Proportional‐hazards analysis revealed that clinical stage was significantly associated with cancer‐specific death, but EGFR expression was not.

Conclusion

Although positive immunostaining for EGFR was more frequent in higher stages of locally advanced bladder cancer, this variable was not an independent predictor of outcome after cystectomy.