bluuebunny/crossref_metadata_2025 huggingface dataset:
Holmium laser prostatectomy
Authors: Tan A.H.H. , Gilling P.J.
Published: September 2003

There are three very different topics presented in this section. The authors from Tauranga, New Zealand, who write about holmium laser prostatectomy, have the largest series in the world and were the instigators of this type of treatment for BPH. They address the pros and cons of treating prostatic enlargement in this way and update the reader on the results.

Urinary markers for urothelial cancer have been introduced in some numbers in recent years. That so many have been developed leaves one with the feeling that none is completely reliable. The importance to urologists of a urinary marker of any malignancy is clear, and the authors from Ankara review this interesting topic.

The management of erectile dysfunction is gradually becoming less invasive and less complicated for patients, but is still very important to urologists worldwide. Many new types of treatment have been recently introduced, and there appear to be more on the way. The authors from New York review the newer agents used for the treatment of sexual dysfunction.
Mentored retroperitoneal laparoscopic renal surgery in children: a safe approach to learning
Authors: Farhat W. , Khoury A. , Bagli D. , McLorie G. , El‐Ghoneimi A.
Published: September 2003

Minimally invasive surgery is not exclusive to the treatment of adult conditions. It has also been used in paediatric urology, and the authors from Toronto and Paris describe a mentorship‐training model for laparoscopic retroperitoneal surgery. They confirmed that a mentored approach is the way to develop this procedure. They also found that ablative procedures are learned relatively early, but that reconstructive procedures require a high degree of skill in laparoscopic techniques, requiring formal training focusing mainly on suturing techniques.

OBJECTIVE

To review the feasibility of introducing advanced retroperitoneal renal laparoscopic surgery (RRLS) to a paediatric urology division, using the mentorship‐training model. Although the scope of practice in paediatric urology is currently adapting endoscopic surgery into daily practice, most paediatric urologists in North America have had no formal training in laparoscopic surgery.

METHODS

The study included four paediatric urologists with 3–25 years of practice; none had had any formal laparoscopic training or ever undertaken advanced RRLS. An experienced laparoscopic surgeon (the mentor) assisted the learning surgeons over a year. The initial phases of learning incorporated detailed lectures, visualization through videotapes and ‘hands‐on’ demonstration by the expert in the technique of the standardized steps for each type of surgery. Over 10 months, ablative and reconstructive RRLS was undertaken jointly by the surgeons and the mentor. After this training the surgeons operated independently. To prevent lengthy operations, conversion to open surgery was planned if there was no significant progression after 2 h of laparoscopic surgery.

RESULTS

Over the 10 months of mentorship, 36 RRLS procedures were undertaken in 31 patients (28 ablative and eight reconstructive). In all cases the mentored surgeons accomplished both retroperitoneal access and the creation of a working space within the cavity. The group was able to initiate ablative RRLS but the mentor undertook all the reconstructive procedures. After the mentorship period, over 10 months, 12 ablative procedures were undertaken independently, and five other attempts at RRLS failed.

CONCLUSION

Although the mentored approach can successfully and safely initiate advanced RRLS in a paediatric urology division, assessing the laparoscopic practice pattern after mentorship in the same group of trainees is warranted. Ablative RRLS is easier to learn for the experienced surgeon, but reconstructive procedures, e.g. pyeloplasty, require a high degree of skill in laparoscopic technique, which may only be acquired through formal training focusing primarily on suturing techniques.
Urinary morbidity after 125I brachytherapy of the prostate
Authors: Mallick S. , Azzouzi R. , Cormier L. , Peiffert D. , Mangin PH.
Published: September 2003

OBJECTIVE

To assess urinary morbidity within the first 6 months after transperineal prostate brachytherapy (TPBT) with 125I for localized prostate adenocarcinoma.

PATIENTS AND METHODS

Between September 2000 and July 2001, 50 consecutive patients with favourable early‐stage prostate cancer were treated with TPBT. Clinical and objective investigations, including uroflowmetry and postvoid residual urine measurements, were evaluated for short‐term urinary morbidity; predictive factors were also sought.

RESULTS

Thirty‐eight (76%) patients developed urinary disorders, but severe urinary complications were exceptional. The International Prostate Symptom Score (IPSS) changed significantly during the first and third month after implantation and then improved during the sixth month. Concomitantly, the maximum and the average urinary flow rate deteriorated significantly. The variations in postvoid residual were less significant. An initial IPSS of> 8 and previous α‐blocker treatment were identified as significant predictive factors of urinary morbidity, as were the TPBT dose received by 90% of the target volume and by 30% of the urethra, and the volume of prostate receiving 144 Gy.

CONCLUSION

Urinary morbidity after TPBT is frequent but rarely exceptionally severe; patients must therefore be given full information. Patients with a higher initial IPSS or having had previous α‐blocker treatment, with their associated dosimetric factors, are at greater risk of these urinary morbidity.
The role of self‐help groups in educating and supporting patients with prostate cancer and interstitial cystitis
Authors: Breau R.H. , Norman R.W.
Published: September 2003

OBJECTIVES

To identify and compare the needs of patients with prostate cancer or interstitial cystitis (IC), and to evaluate the role of self‐help groups (SHGs) in meeting those needs, as SHGs are thought to be an important source of information and social support for such patients.

METHODS

The authors attended SHG meetings for prostate cancer and IC from September 2000 to May 2001. Issues related to SHGs were addressed by combining their experiences with those published previously.

RESULTS

Patients with prostate cancer appear to use SHGs primarily as a medium for advocacy and information sharing about the disease, whereas patients with IC seem to use SHGs for social support and coping skills. Patients perceive SHGs as being useful, but many do not attend these meetings. Urologists’ attitudes toward SHGs are identified as a potential factor contributing to the under‐use of SHGs by both groups of patients.

CONCLUSIONS

The inherent differences in disease and patient characteristics result in both groups of patients using SHGs for different reasons. The differences in therapeutic objectives are reflected in the format and content of SHG meetings. Issues related to not participating in SHGs and areas of future research are discussed.
Prostatic epithelial and luminal area in the transition zone acini: morphometric analysis in normal and hyperplastic human prostate
Authors: Babinski M.A. , Chagas M.A. , Costa W.S. , Sampaio F.J.
Published: September 2003

OBJECTIVE

To analyse quantitatively the acini and changes in the acinar epithelium and lumen in the transitional zone of normal and hyperplastic human prostates.

PATIENTS AND METHODS

Tissue samples of the transitional zone were taken from prostates with benign prostatic hyperplasia (BPH) obtained from 20 patients with clinical symptoms of bladder outlet obstruction who underwent open prostatectomy. The control tissue comprised 20 transitional zones of prostates obtained during autopsy of adults aged < 30 years (killed in accidents). The following variables were measured; the number of acini, total acinar area, area of the lumen, epithelial area, and the median (range) epithelial height, using computerized histomorphometric techniques.

RESULTS

The total area of the acini and the luminal area was statistically significantly greater in BPH. In normal and hyperplastic prostates, respectively, the total mean (sd) area (mm2) of the acini was 0.041 (0.007) and 0.056 (0.016), of the lumen was 0.016 (0.003) and 0.036 (0.013), and of the epithelium was 0.025 (0.004) and 0.019 (0.003) (all P < 0.001). There was no statistically significant difference in the number of acini between controls and BPH. The area and the height of the acinar epithelium was statistically significantly greater in BPH; for epithelial height (µm) in normal and BPH tissue, respectively the minimum height was 9.92 (1.67) and 6.45 (1.14), the maximum 54.38 (4.09) and 41.52 (4.51) and the median 27.89 (2.48) and 19.96 (2.20) (all P < 0.001).

CONCLUSIONS

There was no significant difference in the number of acini between control and BPH tissue, but the area and the height of the acinar epithelium was significantly lower in BPH.
Disturbed pituitary‐testicular axis inhibits testicular descent in the prenatal rat
Authors: Shono T. , Suita S.
Published: September 2003

OBJECTIVE

To investigate whether prenatal stress affects the pituitary‐testicular axis in relation to testicular descent in rat fetuses, as maternal stress can alter the plasma testosterone concentration and inhibit testicular descent in male rat fetuses.

MATERIALS AND METHODS

Pregnant rats were divided into two groups and kept in reverse light‐dark cycles, with lights‐off at 08.00 hours and on at 20.00 hours. In group 1, 15 pregnant females were placed three times daily for 60 min each session in plastic rat‐holders (13 × 6 × 8 cm) illuminated by two 150‐W flood lights during the dark phase, from day 14 to 18 of gestation. In group 2, 10 pregnant females were not handled and thus were used as controls. At 19 days of gestation, five pregnant rats had a Caesarean section in each group, and both testes and the pituitary gland were removed from male fetuses at 10.00–11.00 hours. The tissue homogenates were analysed for testicular testosterone and pituitary luteinizing hormone (LH) by a radioimmunoassay. Thereafter, at 21 and 30 days of age, testicular descent was assessed in the remaining male offspring. Student'st‐ and the chi‐square test were used to assess the results.

RESULTS

The mean (sd) concentration of fetal testicular testosterone was significantly lower in group 1, at 312.9 (26.2) pg/mg, than in group 2, at 532.5 (18.2) pg/mg (P < 0.05); that of pituitary LH was also significantly lower in group 1, at 130.6 (22.7) and 295.6 (35.2) pg/mg, respectively (P < 0.05). The completion rate of testicular descent was 14% in group 1 (36 male rats) and 64% in group 2 (28 male rats) at 21 days old, and thereafter they were 81% and 100%, respectively, at 30 days old (P < 0.05).

CONCLUSION

Maternal stress might inhibit the pituitary‐testicular axis, thereby resulting in abnormal testicular descent in male fetuses.
Urethrocutaneous fistula repair after hypospadias surgery
Authors: Cimador M. , Castagnetti M. , De Grazia E.
Published: September 2003

OBJECTIVE

To evaluate and compare the success rates of simple and layered repairs of urethrocutaneous fistulae after hypospadias repair.

PATIENTS AND METHODS

The charts of 72 children who developed fistulae after hypospadias repair were reviewed; 39 had a simple closure of the fistula, whereas 32 had a ‘pants over vest’ repair, in all cases after excluding an impairment of urine outflow.

RESULTS

The success rate at the first attempt was 74% for simple closure and 94% for the layered repair; at the second attempt it was 80% and 100%, the difference being statistically significant for both repairs.

CONCLUSIONS

Although probably far from an optimal technique for repairing urethrocutaneous fistulae, the pants‐over‐vest repair allows a good success rate for penile shaft fistulae.
Open mini‐access ureterolithotomy: the treatment of choice for the refractory ureteric stone?
Authors: Sharma D.M. , Maharaj D. , Naraynsingh V.
Published: September 2003

OBJECTIVE

To report the experience in one centre of the efficacy and safety of open mini‐access ureterolithotomy (MAU) and to discuss relevant current indications.

PATIENTS AND METHODS

MAU was undertaken in 112 patients (mean age 38 years, range 26–57) between 1991 and 2001; the details and outcomes are reviewed. The mean (range) stone size was 12 (8–22) mm, with 30 stones in the upper, 69 in the mid‐ and 13 in the lower ureter. In 15 cases the stones were impacted and there were signs of infection in the proximal ureter.

RESULTS

MAU was successful in 111 patients; the one failure was caused by proximal stone migration early in the series. The mean (range) operative duration was 28 (10–44) min and the hospital stay 42 (24–72) h; 33 patients were in hospital for 24 h, 72 for 48 h and seven for 72 h. The blood loss was minimal, at 50 (30–150) mL. The drain was removed after 5 (5–7) days. Patients reported using opioid or nonsteroidal anti‐inflammatory analgesia for a mean of 4 (1–7) days after surgery. The mean time to resumption of work was 16 (8–35) days.

CONCLUSIONS

MAU is a safe and reliable minimally invasive procedure; its role is mainly confined to salvage for failed first‐line stone treatments but in selected cases, where a poor outcome can be predicted from other methods, it is an excellent first‐line treatment.
Neurotrophic effects of vascular endothelial growth factor and neurotrophins on cultured major pelvic ganglia
Authors: Lin G. , Chen K.C. , Hsieh P.S. , Yeh C.H. , Lue T.F. , Lin C.S.
Published: September 2003

In a study by researchers from San Francisco and Taiwan, a ganglial culture system is used to screen various growth factors. The aim was to assess these growth factors as possible therapeutic agents for pelvic floors nerve injuries. They found that vascular endothelial growth factor causes a marked neurotrophic effect.

Other researchers from Ann Arbor describe a method of immobilising extracellular matrix proteins to potential growth surfaces, and found that this enhances the attachment of cultured cells. They felt that this might lead to the development of other methods of tissue engineering.

The authors from Japan describe a study wherein they investigated whether prenatal stress affected the pituitary‐testicular axis and thus testicular descent in rat fetuses; they report that this may indeed be the mechanism.

OBJECTIVE

To investigate the feasibility of using a ganglial culture system to screen various growth factors as potential therapeutic agents for pelvic nerve injuries.

MATERIALS AND METHODS

The major pelvic ganglia (MPG) were isolated from male rats and attached to culture dishes with the aid of MatrigelTM (Becton Dickinson, Mountain View, CA, USA). Alternatively, the dorso‐caudal region (DCR) of MPG, from which the cavernous nerves originate, was dissected and then attached to a Matrigel‐coated coverslip. The MPG or DCR was cultured in serum‐free medium supplemented with phosphate‐buffered saline (PBS, control), 50 ng/mL of vascular endothelial growth factor (VEGF), 20 ng/mL of a neurotrophin (BDNF, NT3, or NT4), or combinations of these growth factors. After 2 days of incubation, the ganglial tissues with their outgrowing nerve fibres were stained for the expression of NADPH‐diaphorase, tyrosine hydroxylase (TH) and acetylcholinesterase (AChE). The length and staining intensity of nerve fibres were analysed.

RESULTS

The outgrowing fibres were significantly longer in MPG treated with any of the four tested growth factors than in PBS‐treated MPG. The combination of VEGF and NT3 induced the best fibre growth. Improvements to the culturing conditions allowed a histological examination of the outgrowing fibres for the expression of nitric oxide synthase (NOS), TH and AChE. VEGF and BDNF were equally capable of inducing NOS‐ and TH‐expressing fibres. BDNF was much weaker than VEGF for inducing AChE‐expressing fibres.

CONCLUSIONS

This improved culturing system is potentially useful for screening nerve‐regenerating factors; VEGF had neurotrophic effects comparable with BDNF, NT3, or NT4.
Effectiveness of intravesical resiniferatoxin in treating detrusor hyper‐reflexia and external sphincter dyssynergia in patients with chronic spinal cord lesions
Authors: Kuo H.‐C.
Published: September 2003

OBJECTIVE

To investigate the therapeutic effect of resiniferatoxin in patients with chronic spinal cord lesions, as detrusor hyper‐reflexia and external sphincter dyssynergia (DESD) are common phenomenon in such patients.

PATIENTS AND METHODS

Twenty patients with chronic spinal cord lesions and DESD refractory to anticholinergic treatment were enrolled in a prospective study. They were treated with 30 mL of 10 µmol/L resiniferatoxin for 30 min. Four types of response were recorded during instillation: type 1, a sustained high‐pressure detrusor contraction followed by complete acontractility; type 2, a high‐pressure contraction followed by progressively lower contractions; type 3, intermittent high‐pressure detrusor contractions throughout the instillation; type 4, intermittent low‐pressure detrusor contractions. The changes in clinical symptoms and urodynamics at baseline, during resiniferatoxin instillation and 1 month after treatment were compared.

RESULTS

All patients had DESD and 10 had autonomic dysreflexia; 18 had urinary incontinence and 13 had difficult urination. Continence and/or difficult urination improved in 12 patients, including all five with type 1, four with type 2, two with type 3 and only one with a type 4 response. Four patients became dry during the day and eight had less urgency and fewer incontinence episodes, and a significantly increased voided volume. Of the 13 patients who complained of difficult urination, eight had an improvement either by spontaneous voiding (five) or the Crede manoeuvre to voiding (three). The mean (sd) maximum cystometric capacity increased significantly after treatment, from 102.1 (31.5) to 236.6 (88.6) mL (P < 0.001), but the detrusor pressure showed no significant change, at 55.9 (23.2) to 47.5 (28.1) cmH2O. The external urethral sphincter showed intermittent activity during reflexic detrusor contractions at baseline.

CONCLUSION

Resiniferatoxin at 10 µmol/L has a clinical effect on two‐thirds of patients with a spinal cord lesion and detrusor hyper‐reflexia, but not on the DESD. The initial response to resiniferatoxin instillation might predict a favourable therapeutic outcome.
Is the conservative management of chronic retention in men ever justified?
Authors: Bates T.S. , Sugiono M. , James E.D. , Stott M.A. , Pocock R.D.
Published: September 2003

OBJECTIVE

To assess the outcome of men presenting with lower urinary tract symptoms (LUTS) associated with large postvoid residual urine volumes (PVR).

PATIENTS AND METHODS

The study included men presenting with LUTS and a PVR of > 250 mL who, because of significant comorbidity, a low symptom score or patient request, were managed conservatively and prospectively, and were followed with symptom assessment, serum creatinine levels, flow rates and renal ultrasonography. Patients were actively managed if there was a history of previous outflow tract surgery, prostate cancer, urethral strictures, neuropathy, elevated creatinine or hydronephrosis. In all, 93 men (mean age 70 years, range 40–84) with a median (range) PVR of 363 mL (250–700) were included in the study and followed for 5 (3–10) years. At presentation, the median maximum flow rate was 10.2 (3–30) mL/s and the voided volume 316 (89–714) mL.

RESULTS

The measured PVR remained stable in 47 (51%), reduced in 27 (29%) and increased in 19 (20%) patients; 31 patients (33%) went on to transurethral resection of the prostate after a median of 30 (10–120) months, because of serum creatinine elevation (two), acute retention (seven), increasing PVR (eight) and worsening symptoms (14). Of 31 patients 25 were available for evaluation after surgery; their median PVR was 159 (0–1000) mL, flow rate 18.4 (4–37) mL/s and voided volume 321 (90–653) mL. Symptoms were improved in all but five men. There was no difference in initial flow rate, voided volume or PVR between those who developed complications or went on to surgery and those who did not. Urinary tract infections (UTIs) occurred in five patients and two developed bladder stones.

CONCLUSIONS

Complications such as renal failure, acute retention and UTIs are uncommon in men with large, chronic PVRs. Conservative management for this group of patients is reasonable but outpatient review is prudent. There were no factors that could be used to predict those patients who eventually required surgery.
Quality of care for patients with Type 2 diabetes mellitus—a long‐term comparison of two quality improvement programmes in the Netherlands
Authors: Renders C. M. , Valk G. D. , De Sonnaville J. J. J. , Twisk J. , Kriegsman D. M. W. , Heine R. J. , Van Eijk J. Th. M. , Van Der Wal G.
Published: September 2003

Aim  To compare two intervention programmes, aimed at improving the quality of care provided for patients with Type 2 diabetes in the longer term.

Methods  A retrospective comparison of data derived from two non‐randomized trials with 3.5 years of follow‐up. In the first intervention group 401 patients were included, 413 in the second intervention group and 105 in the reference group. The first programme focused on improving the skills and knowledge of general practitioners (GPs) with regard to Type 2 diabetes, and supported them in making organizational changes in their practice (GP care only). Centralized shared diabetes care was implemented in the second programme in which the GPs received therapy advice according to a protocol for each individual patient. The patients were also encouraged in self‐management, and received structured diabetes education (Diabetes Service). The main patient outcomes were HbA1c, blood pressure and serum lipid levels. Multilevel analysis was applied to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices.

Results  The HbA1c levels of patients of GPs who were supported by the Diabetes Service improved significantly more than the HbA1c levels of patients receiving GP care only {−0.28%[95% confidence interval (CI) −0.45; −0.11]}. In contrast, the systolic blood pressure of patients receiving GP care only decreased more than that of patients of GPs supported by the Diabetes Service [4.14 mmHg (95% CI 1.77, 6.51)].

Conclusion  A Diabetes Service, providing GPs with individual therapy advice and patient education, resulted in better glycaemic control over 3.5 years than an intervention aimed at improving the skills of GPs in combination with organizational changes in the general practice.
Screening for diabetic retinopathy: a cause for concern in people who drive
Authors: Razvi S. , Myers L. , Patton K. , McCulloch A. J.
Published: September 2003

Aims  To report a case of a road traffic accident in a lady driving home from a diabetes clinic after pupillary dilatation. We also present the findings of a questionnaire survey of health professionals to elicit their practice in dealing with such patients.

Methods  We present the case report of a lady having a road traffic accident on her way back from a retinal screening appointment after having had pupillary dilatation. A subsequent postal questionnaire survey was undertaken to find out current practice in screening patients who drive on the day of their retinal screening.

Results  A lady was involved in a road traffic accident whilst returning home after retinal screening. Her motor insurance company refused to cover subsequent claims for damage because her pupils had been dilated. She was also prosecuted by the police for driving without valid motor insurance. We conducted a postal survey of 500 health care workers including ophthalmologists, optometrists, diabetologists and general practitioners regarding the use of dilating drops in people with diabetes who intend to drive. Analysis of 320 valid responses confirmed that there is no consistent practice with regard to either the use of dilating drops in drivers or in ensuring that arrangements are made for subsequent adequate visual inspection in those whom dilatory drops are not instilled.

Conclusions  Guidelines, for use by health care professionals and people with diabetes, are clearly required regarding the use of pupillary dilating drops in drivers.
Insulin and lysophosphatidylcholine synergistically stimulate NO‐dependent cGMP production in human endothelial cells
Authors: Konopatskaya O. , Whatmore J. L. , Tooke J. E. , Shore A. C.
Published: September 2003

Aims  Nitric oxide (NO) is an important regulator of cardiovascular homeostasis. Lysophosphatidylcholine (lyso‐PC), a major constituent of oxidized low density lipoproteins (oxLDL), has been reported to impair nitric oxide‐dependent vasodilatation. This study investigated the possible mechanism of the lyso‐PC effect on insulin‐stimulated NO‐dependent of cyclic guanosine 3′,5′‐monophosphate (cGMP) generation in human endothelial cells.

Methods  The intracellular concentration of cGMP in cultured human umbilical vein endothelial cells (HUVECs) was used to estimate NO production. The levels of endothelial nitric oxide synthase (eNOS) protein expression were assessed by Western blotting analyses.

Results  Both insulin, at physiological concentration, and lyso‐PC stimulated rapid and prolonged intracellular of cGMP production, and together induced a marked synergistic response (for short‐term stimulation: 1185 ± 285.9% over control level (100%) compared with insulin and lyso‐PC alone (384.8 ± 67.4% and 357 ± 205%, respectively; P < 0.001), for long‐term stimulation: 3495 ± 1377%, compared with insulin and lyso‐PC alone (663 ± 131% and 487 ± 250%, P = 0.002)). Stimulated levels of cGMP accumulation were completely abrogated by NOS inhibitor, indicating NO involvement in the effects of insulin and lyso‐PC. Stimulated NO synthesis was not associated with altered eNOS protein expression. Cell subfractionation studies demonstrate that insulin and lyso‐PC each alone induced translocation of eNOS from the membrane to the cytosolic compartment and together caused a synergistic translocation.

Conclusions  The presented data suggest that insulin and lyso‐PC synergistically upregulate endothelial NO production via eNOS translocation from the membrane fraction to the cytosol. This study raises the possibility that an interplay between various factors accompanying diabetes can lead to endothelial NO overproduction or desensitization of NO‐dependent responses. Appropriate rather than necessarily high levels of nitric oxide is the determinant of vascular health.
The ultrasound assessment of adipose tissue deposition in fetuses of ‘well controlled’ insulin‐dependent diabetic pregnancies
Authors: Greco P. , Vimercati A. , Hyett J. , Rossi A. C. , Scioscia M. , Giorgino F. , Loverro G. , Selvaggi L.
Published: September 2003

Objective  To assess differences in adipose deposition in fetuses from normal pregnancies and women with diabetes.

Research design and methods  The study group consisted of 15 well controlled insulin‐dependent women with diabetes and 16 controls with a normal glucose. Ultrasound measurements were taken of subcuticular tissue thickness at the abdominal and suprascapular level at 31 and 37 weeks gestation. Triceps and subscapular skinfold thickness were also measured at birth.

Results  Gestational age at delivery and birthweights were not significantly different. At 31 weeks, fasting glucose levels were 5.0 ± 1 mmol/l for diabetic vs. 3.3 ± 0.3 mmol/l for controls (P < 0.01), post‐prandial 5.6 ± 0.4 vs. 5.1 ± 0.3 mmol/l (P < 0.01). At 37 weeks, they were 4.6 ± 0.2 mmol/l vs. 3.8 ± 1.1 mmol/l (P < 0.01) and 6.0 ± 0.6 mmol/l vs. 5.3 ± 0.3 mmol/l (P < 0.01). Abdominal and suprascapular subcuticular thickness were 4.4 ± 0.1 mm vs. 3.7 ± 0.1 mm (P < 0.05) and 4.3 ± 0.2 mm vs. 3.5 ± 0.2 mm (P < 0.05) at 31; 5.6 ± 0.2 mm vs. 4.8 ± 0.1 mm (P < 0.05) and 5.4 ± 0.2 mm vs. 4.4 ± 0.1 mm (P < 0.05) at 37 weeks. At birth, triceps and suprascapular skinfolds were 4.7 ± 0.1 mm vs. 4.1 ± 0.1 mm (P < 0.05) and 4.7 ± 0.2 mm vs. 3.8 ± 0.1 mm (P < 0.01).

Conclusion  Adipose tissue disposition is increased in fetuses of women with well‐controlled diabetes. This may be a reflection of higher maternal glucose levels in these women and may explain why even well‐controlled diabetic pregnancies are at risk of macrosomia.
Serum leptin is elevated in Saudi Arabian patients with metabolic syndrome and coronary artery disease
Authors: Al‐Daghri N. , Al‐Rubean K. , Bartlett W. A. , Al‐Attas O. , Jones A. F. , Kumar S.
Published: September 2003

Aims  To compare plasma leptin in Saudi subjects with Type 2 diabetes and coronary heart disease (CHD) with non‐diabetic control subjects and to examine the relationship of plasma leptin to other CHD risk factors.

Research design and method  Serum leptin concentrations were measured in 144 Saudi men. Subjects studied included 59 with Type 2 diabetes mellitus [BMI 27.5 (3.7) kg/m2 mean (sd)], 34 with coronary heart disease [BMI 29.6 (1.8) kg/m2], and 51 non‐diabetic controls [BMI 28.0 (3.5) kg/m2]. There was no significant difference in BMI between the groups. Fasting serum leptin, lipids, insulin, apolipoproteins and glucose were measured. BMI, blood pressure; smoking habit and age were also recorded. Insulin resistance was assessed using the HOMA model.

Results  Leptin concentrations were significantly higher in diabetic and CHD patients than in controls (P = 0.024 and 0.016, respectively). Multiple regression analysis showed that body weight (P < 0.0006), serum triglyceride concentration (P = 0.046) and systolic blood pressure (P = 0.013) were all significantly related to the logarithm of the serum leptin concentration (R2 = 0.549) in CHD patients. A subgroup analysis, comparing those patients who had the metabolic syndrome, as defined by WHO, with controls, showed higher serum leptin in those with metabolic syndrome (P = 0.05).

Conclusions  Serum leptin is increased in Saudi subjects with diabetes mellitus, metabolic syndrome and CHD. Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance. Further studies are needed to evaluate this relationship prospectively.
Serum resistin level in essential hypertension patients with different glucose tolerance
Authors: Zhang J.‐L. , Qin Y.‐W. , Zheng X. , Qiu J.‐L. , Zou D.‐J.
Published: September 2003

Aims  To investigate resistin concentrations in patients with essential hypertension and different glucose tolerance and the relationship between serum resistin level and blood glucose.

Methods  Sixty‐five patients with essential hypertension [13 with Type 2 diabetes mellitus (DM), 26 with impaired glucose tolerance (IGT), and 26 with normal glucose tolerance (NGT); 30 males, 35 females] were studied. Fasting serum resistin concentrations were measured by enzyme immunoassay (EIA). Oral glucose tolerance tests and insulin release tests were used to calculate glucose area under the curve (AUCG), the ratio of insulin to glucose (ΔI30/ΔG30), and insulin sensitivity index (ISI) according to Cederholm's formula.

Results  Fasting serum resistin concentrations (µg/l) in DM (34.9 ± 10.2) patients were significantly higher than those in IGT (25.1 ± 10.4) (P < 0.05) and in NGT (21.5 ± 7.9) (P < 0.05) patients. Pearson correlation showed that fasting serum resistin concentration was correlated with AUCG (r = 0.445, P < 0.001), ISI (r = −0.322, P < 0.01) and ΔI30/ΔG30 (r = −0.366, P < 0.01), but not body mass index and waist‐hip ratio. After adjustment for gender, age and body mass index (BMI), partial correlation analysis showed that the fasting serum resistin concentrations were still correlated with AUCG (r = 0.327, P < 0.01) and ΔI30/ΔG30 (r = −0.348, P < 0.01), but ISI.

Conclusion  Resistin may be involved in the development of diabetes in humans.
A qualitative investigation of the views and health beliefs of patients with Type 2 diabetes following the introduction of a diabetes shared care service
Authors: Smith S. M. , O'Leary M. , Bury G. , Shannon W. , Tynan A. , Staines A. , Thompson C.
Published: September 2003

Aims  A qualitative research approach was adopted in order to explore the views and health beliefs of patients with Type 2 diabetes who had experienced a new structured diabetes shared care service.

Methods  Patients from 15 general practices were randomly selected and invited to attend three focus groups. Two independent researchers adopted the ‘Framework’ technique to analyse the transcribed data and identify key themes expressed by patients.

Results  Themes relating to diabetes included frustration, victimization and powerlessness in relation to living with diabetes, controlling blood sugar, medication and economic barriers to care. Differences in emphases between patients and healthcare providers emerged. Patients were generally positive about shared care and largely identified it with the nurses involved.

Conclusion  This research highlights the importance of an in‐depth exploration of patients’ views during changes in diabetes care delivery to identify service delivery failures and gaps in patient knowledge such as lack of awareness of the extent of macrovascular risk.
5-HT1F Receptor Agonists in Acute Migraine Treatment: A Hypothesis
Authors: Ramadan NM , Skljarevski V , Phebus LA , Johnson KW
Published: September 2003

Serotonin-1F receptor (5-HT1F) agonists may relieve acute migraine without vasoconstriction. We conducted a review of preclinical and clinical data that assessed the potential link between migraine and 5-HT1F activation. (i) A high correlation exists between the potency of various 5-HT1 receptor agonists in the guinea pig dural plasma protein extravasation assay and their 5-HT1F receptor binding affinity. (ii) 5-HT1F receptors are on the trigeminal system, and may participate in blocking migraine pain transmission through the trigeminal ganglion and nucleus caudalis. (iii) 5-HT1F receptors are located on glutamate-containing neurones and their activation might inhibit glutamate release; glutamate excess may play a role in migraine. (iv) Selective 5-HT1F receptor agonists (LY334370; LY344864) are effective in preclinical migraine models and are non-vasoconstrictive. (v) LY334370 is effective in acute migraine, and does not cause any symptoms/signs of coronary vasoconstriction. Preclinical experiments and clinical observations argue for a role of selective 5-HT1F agonists in migraine.
An Analysis of Clinical Characteristics in Genetically Linked Migraine-Affected Pedigrees
Authors: Lea RA , Hilton DA , MacMillian JC , Griffiths LR
Published: September 2003

Migraine is a common complex disorder characterized by severe recurrent headache and usually accompanied by nausea and vomiting. Previous studies in our laboratory have utilized three large multigenerational Australian pedigrees affected with migraine to indicate that the disease is genetically heterogeneous, with linkage results implicating genomic susceptibility regions on both chromosomes 19p and Xq. The present study explores the possibility of a correlation between genetic and clinical heterogeneity in these affected pedigrees. Specifically, the clinical characteristics of migraine including subtype, age of onset, frequency, duration, and disease symptoms were compared between the migraine pedigrees, and gender differences were also assessed. Our exploratory analyses revealed no significant differences in any of the clinical characteristics tested between the chromosome 19-linked family and the two X-linked families. Also, we did not detect any differences in male vs. female clinical features for these pedigrees. In conclusion, migraine is considered to be a clinically and genetically heterogeneous disorder; however, our study provided no conclusive evidence that variation in genomic susceptibility region is related to heterogeneity at the clinical level in these migraine-affected pedigrees.
Abnormal Habituation of ‘nociceptive’ Blink Reflex in Migraine-Evidence for Increased Excitability of Trigeminal Nociception
Authors: Katsarava Z , Giffin N , Diener H-C , Kaube H
Published: September 2003

We studied the habituation of the ‘nociceptive’ blink reflex (nBR) in 15 healthy subjects and 17 migraine patients interictally as well as during unilateral migraine headache within six hours of onset and after treatment. In healthy volunteers the mean regression coefficient (MRC) was – 3.9 following right sided and – 4.9 left sided stimulation. This equals an amplitude loss of 19.5% (5 X −3.9) and 24.5% (5 X −4.9), respectively, across five consecutive sweeps. An augmentation of nBR responses was found in migraine patients interictally: MRC = 3.3 following stimulation of the headache side (HA) and MRC = 4.0 of the non-headache side (non-HA). The differences were statistically significant (ANOVA: d.f. = 1, F = 25.8, P < 0.001). During the migraine attack MRCs were negative both before (−5.0, HA and – 4.0, non-HA) and after treatment (−2.6, HA and −1.9 non-HA) and significantly differed from those outside the migraine attack (ANOVA: d.f. = 2, F = 12.4, P < 0.001). The demonstrated lack of habituation of the nBR responses indicates an abnormal trigeminal nociceptive processing in migraine patients outside the migraine attack.
Topiramate in the Treatment of Chronic Migraine
Authors: Silvestrini M , Bartolini M , Coccia M , Baruffaldi R , Taffi R , Provinciali L
Published: September 2003

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean ± SD: 20.9 ± 3.2 and 20.8 ± 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache ± SD: 8.1 ± 8.1 vs. 20.6 ± 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.
Recovery of brain docosahexaenoate leads to recovery of spatial task performance
Authors: Moriguchi Toru , Salem Norman
Published: September 2003

Infants fed vegetable oil‐based formulas may have poorer visual function, lower cognitive scores and acquire learning tasks more slowly in comparison with those breast fed or those fed formulas supplemented with docosahexaenoate. The aim of the present study was to determine the reversibility of losses in brain function associated with the loss of brain DHA. Rats were fed very low or adequate levels of n‐3 fatty acids through three generations. The n‐3 fatty acid deficient animals of the F3 generation were then given an n‐3 adequate diet containing alpha‐linolenic and docosahexaenoic acids (DHA) at birth, weaning (3 weeks) or young adulthood (7 weeks). The spatial task performance of these animals returned to the n‐3 adequate diet was then compared using the Morris water at two different ages, at 9 or 13 weeks. Our results indicate that animals repleted since birth or at weaning were able to achieve nearly the same level of brain DHA and spatial task performance as animals maintained for three generations on an n‐3 adequate diet. In the case of young adult animals, the degree of DHA and behavioral performance recovery depended upon the duration of dietary repletion with substantial recovery in animals after 6 weeks but little recovery of function after two weeks. The significance of these findings is that they indicate that at least some of the adverse effects of DHA deficiency during neurodevelopment may be reversible with an n‐3 fatty acid supplemented diet.
On high‐ and low‐affinity agonist sites in GABAA receptors
Authors: Baur Roland , Sigel Erwin
Published: September 2003

GABAA receptors are activated via low‐affinity binding sites for the agonists GABA or muscimol. Evidence has been provided that the amino acid residueα1F64 located at the β2(+)/α1(–) subunit interface forms part of this binding site. In radioactive ligand binding studies the agonist [3H]muscimol has been found to interact with the receptor via a high‐affinity binding site. This site has been interpreted as a conformational variant of the low‐affinity site. Alternatively, the high‐affinity binding site has been located to the α1(+)/β2(–) interface and the homologous residue to α1F64, β2Y62 has been proposed to constitute an important part of this site. Here we investigated the effect of the point mutation α1F64L and the homologous mutation β2Y62L on agonist and antagonist binding and functional properties in α1β2γ2 GABAA receptors. While the mutation in the α1 subunit had drastic consequences on all studied properties, including desensitization, the mutation in the β2 subunit had little consequence. Our observations are relevant for the relative location of high‐ and low‐affinity agonist sites in GABAA receptors.
Changes in cortical acetyl‐CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG‐saporin
Authors: Tomaszewicz Maria , Roßner Steffen , Schliebs Reinhard , Ćwikowska Justyna , Szutowicz Andrzej
Published: September 2003

The aim of the present study was to reveal whether reduced cortical cholinergic input affects the acetyl‐CoA metabolism in cholinoceptive cortical target regions which may play a causative role for the deficits in cerebral glucose metabolism observed in Alzheimer's disease. The effect of cortical cholinergic denervation produced by a single intracerebroventricular application of the cholinergic immunotoxin 192IgG‐saporin, on activities of pyruvate dehydrogenase and adenosine triphosphate (ATP)‐citrate lyase as well as on the level of synaptoplasmic and mitochondrial acetyl‐CoA and acetylcholine release in cortical target regions was studied. Cholinergic lesion produced 83%, 72% and 32% decreases in the activities of choline acetyltransferase, acetylcholinesterase and ATP‐citrate lyase in nerve terminals isolated from rat brain cortex, respectively, but no change in pyruvate dehydrogenase activity. Spontaneous and Ca2+‐evoked acetylcholine release from synaptosomes was inhibited by 76% and 73%, respectively, following immunolesion. The lesion‐induced 39% decrease of acetyl‐CoA level in synaptosomal mitochondria was accompanied by 74% increase in synaptoplasmic fraction. Levels of acetyl‐CoA and CoASH assayed in fraction of whole brain mitochondria from lesioned cortex were 61% and 48%, respectively, higher as compared to controls. The data suggest a preferential localization of ATP‐citrate lyase in cholinergic nerve terminals, where it may contribute to the transport of acetyl‐CoA from the mitochondrial to the cytoplasmic compartment. They provide evidence on differential distribution of acetyl‐CoA in subcellular compartments of cholinergic and non‐cholinergic nerve terminals. There are also indications that cholinergic activity affects acetyl‐CoA level and its intracellular distribution in glial and other non‐cholinergic cortical cells.
P2X7 nucleotide receptor activation enhances IFNγ‐induced type II nitric oxide synthase activity in BV‐2 microglial cells
Authors: Gendron Fernand‐Pierre , Chalimoniuk Malgorzata , Strosznajder Joanna , Shen Siming , González Fernando A. , Weisman Gary A. , Sun Grace Y.
Published: September 2003

Under normal and pathological conditions, brain cells release nucleotides that regulate a wide range of cellular responses due to activation of P2 nucleotide receptors. In this study, the effect of extracellular nucleotides on IFNγ‐induced NO release in murine BV‐2 microglial cells was investigated. BV‐2 cells expressed mRNA for metabotropic P2Y and ionotropic P2X receptors. Among the P2 receptor agonists tested, ATP, ADP, 2′,3′‐O‐(4‐benzoylbenzoyl)‐ATP (BzATP), and 2‐methylthio‐ATP (2‐MeSATP), but not UTP, enhanced IFNγ‐induced iNOS expression and NO production, suggesting that the uridine nucleotide receptors P2Y2 and P2Y6 are not involved in this response. U0126, an antagonist for MEK1/2, a kinase that phosphorylates the extracellular signal‐regulated kinases ERK1/2, decreased IFNγ‐induced NO production. BzATP, a potent P2X7 receptor agonist, was more effective than ATP, ADP, or 2‐MeSATP at enhancing IFNγ‐induced ERK1/2 phosphorylation. Consistent with activation of the P2X7 receptor, periodate‐oxidized ATP, a P2X7 receptor antagonist, and suramin, a non‐specific P2 receptor antagonist, inhibited the effect of ATP or BzATP on IFNγ‐induced NO production, whereas pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS), an antagonist of several P2X receptor subtypes, was ineffective. These results suggest that activation of P2X7 receptors may contribute to inflammatory responses in microglial cells seen in neurodegenerative diseases.
Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi
Authors: Brown Lesley R. , Harris David A.
Published: September 2003

The cellular isoform of prion protein (PrPC) is a plasma membrane glycoprotein whose conformational conversion into PrPSc is the central molecular event in the propagation of infectious prions. However, the physiological function of PrPC has remained uncertain. The finding that PrPC binds copper ions with low micromolar affinity, coupled with several other observations, has led to the proposal that the protein plays a role in copper homeostasis. Using biochemical techniques, we had shown previously that copper ions rapidly and reversibly stimulate endocytosis of PrPC from the cell surface. In this report, we employ immunofluorescence microscopy to further investigate the specificity and kinetics of metal effects on PrPC trafficking and to identify the intracellular compartments to which internalized PrPC is delivered in response to copper and zinc. We find that both of these metals stimulate redistribution of surface PrPC to a subset of transferrin‐containing early endosomes as well as to Golgi compartments. These results are consistent with models in which PrPC plays a role in the cellular uptake or efflux of transition metals.
Pro‐apoptotic protein kinase Cδ is associated with intranuclear inclusions in a transgenic model of Huntington's disease
Authors: Zemskov Evgeny A. , Jana Nihar R. , Kurosawa Masaru , Miyazaki Haruko , Sakamoto Naoaki , Nekooki Munenori , Nukina Nobuyuki
Published: September 2003

In order to investigate any effect of truncated mutant huntingtin (tNhtt) aggregation on protein kinase C (PKC) signaling in Huntington's disease (HD), we studied a possible association of PKC isoforms with the aggregates using cellular and transgenic models of HD. In this report we describe an association of mutant tNhtt with at least three PKC isoforms (α, δ, ζ), as revealed by co‐immunoprecipitation assays and immunocytochemistry in a cellular model of HD (Neuro2a cells expressing tNhtt‐150Q‐EGFP), as well as a specific association of PKCδ with intranuclear aggregates in a transgenic model (R6/2 mice). Immunoblot analysis of isolated nuclear fractions shows an elevation of nuclear PKCδ in transgenic brain tissue. The observed elevation has a strong similarity with the apoptotic translocation of PKCδ detected in experiments with the mouse neuroblastoma Neuro2a cells. Using a Neuro2a cell line expressing tNhtt with the nuclear localization signal, we demonstrate the association of PKCδ with intranuclear aggregates and present evidence that accumulation of PKCδ in cell nuclei does not depend on mutant htt nuclear translocation. Our results suggest that the association of PKCδ with intranuclear htt‐aggregates may affect its apoptotic function in a transgenic model of HD.