bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycometabolic status and acute myocardial infarction: has the time come for glucose‐insulin‐(potassium) therapy?
Authors: Wong V. , Cheung N. W. , Boyages S. C.
Published: September 2003

Abstract

Glucose‐insulin‐potassium infusion as a metabolic therapy was first advocated for the management of acute myocardial infarction (AMI) in 1960s. Over the subsequent decades, enthusiasm for its use has been patchy, especially with the availability of other effective treatments such as reperfusion therapy for AMI. Several clinical studies in the mid‐1990s revived the interest in the glycometabolic aspects of patients with AMI. The somewhat conflicting results of these recent studies have generated debate over the significance of the glycometabolic state following acute coronary occlusion and the role of insulin‐based infusion therapy. Although most of the available evidence is in favour of an insulin‐based therapy, there are still many aspects of this therapy that require clarification. More evidence will be required from further clinical trials before it is adopted in routine clinical practice. (Intern Med J 2003; 33: 443−449)
Evaluation of a warfarin initiation protocol for older people
Authors: Wilkinson T. J. , Sainsbury R.
Published: September 2003

Abstract

A protocol for initiation of warfarin therapy, targeted specifically for older people and based on individual responses to initial warfarin doses, was evaluated in a case‐control study. People within the protocol group: (i) received higher initial doses of warfarin, (ii) reached an international normalized ratio (INR) of 2 more quickly, (iii) spent more time with INR of 2−3 in the first week and (iv) were less likely to be over‐anticoagulated. However, the proportion of people who reached an INR of 2 too quickly (in <4 days) was no greater. The protocol correctly predicted the maintenance dose range of warfarin in over 70% of cases. (Intern Med J 2003; 33: 465−467)
Collective danger and individual risk: cultural perspectives on the hazards of medical research
Authors: Parker D. B. , Barrett R. J.
Published: September 2003

Abstract

Changes in medical research ethics in the past two decades have made the communication of risk to potential participants a legal imperative. Using ethnographic data from two different cultures, we examine the hazards associated with medical research in relation to the respective societal contexts that imbue them with meaning. The Iban, a Dayak people indigenous to Borneo, perceive the hazards of participating in research in terms of danger to the collective. In Australia they are construed in terms of risk to individuals. Risk in medical research is one manifestation of a broader notion of ‘risk’ that is constitutive of the research enterprise itself and, we argue, fundamental to post‐industrial society. (Intern Med J 2003; 33: 463−464)
Heterogeneity of amiodarone‐induced thyrotoxicosis: evaluation of colour‐flow Doppler sonography in predicting therapeutic response
Authors: Wong R. , Cheung W. , Stockigt J. R. , Topliss D. J.
Published: September 2003

Abstract

Background:  Amiodarone‐induced thyrotoxicosis (AIT) presents a therapeutic challenge because of its resistance to standard antithyroid therapy. In iodine‐deplete environments, colour‐flow Doppler sonography (CFDS) has allowed distinction between two types of AIT: (i) Type I AIT, associated with increased vascularity (CFDS I−III) and response to thionamide antithyroid drug and (ii) type II AIT, with no/little thyroid vascularity (CFDS 0) and prednisolone responsiveness.

Aim:  To clarify if CFDS patterns correlated with treatment outcomes in a retrospective study of 24 patients with AIT in an iodine‐replete environment.

Methods:  Medical records of patients who presented to a teaching hospital between January 1998 to December 2000 were reviewed. Results of CFDS, ultrasound measurement of thyroid size and technetium scanning of the thyroid were correlated with treatment responses, especially prednisolone responsiveness.

Results:  Thirteen of 24 patients showed CFDS 0. Twelve of these 13 were evaluable for prednisolone responsiveness, of whom seven (58%) were prednisolone‐responsive. Of 11 patients with CFDS I−III, four (36%) responded to antithyroid medication alone and only one of seven (14%) was prednisolone‐responsive. Euthyroidism was achieved twice as rapidly in patients with CFDS 0 than those with CFDS I‐III. Because of medical treatment failure, seven patients, from both CFDS groups, required urgent near‐total thyroidectomy which was successful and uncomplicated in all cases.

Conclusions:  CFDS is useful in the management of AIT because CFDS 0 correlates better with prednisolone response (58%) than CFDS I−III (14%). However, unlike experience in iodine‐deficient regions, the results of the present study revealed that treatment responses to thionamide or prednisolone were heterogeneous within uniform CFDS patterns. Thus, prednisolone‐­responsiveness was not consistently predicted by CFDS 0, but the presence of flow appeared to correlate with non‐response to prednisolone. (Intern Med J 2003; 33: 420−426)
Decreased prostatic arachidonic acid in human prostatic carcinoma
Authors: Faas F.H. , Dang A.Q. , White J. , Schaefer R.F. , Johnson D.E.
Published: September 2003

OBJECTIVE

To measure prostatic and blood fatty acid composition in a large group of patients undergoing prostatectomy for benign or malignant prostate disease, as there is evidence linking arachidonic acid metabolism and prostate cancer through its role as an eicosanoid precursor, and earlier studies showed lower prostatic arachidonic acid content in a few patients.

PATIENTS AND METHODS

Prostatic phospholipid fatty acid composition was determined in prostate tissue from 173 patients undergoing prostate surgery, i.e. radical prostatectomy, cystoprostatectomy or transurethral resection (TURP). Blood fatty acid composition was determined in 99 of these patients and in 85 undergoing prostatic needle biopsy.

RESULTS

There was a significantly lower percentage of arachidonic acid in malignant than in benign portions of the prostate (15.2% vs 17%) in all patients assessed. The changes were greatest in those undergoing TURP for known prostate cancer (13.4% vs 17.2%), these patients having the greatest proportion of malignancy in the specimens. There were no consistent changes in blood fatty acid composition.

CONCLUSION

This is the first prospective study of arachidonic acids levels involving many consecutive patients undergoing prostate surgery for either benign or malignant disease. The lower prostatic arachidonic acid level is probably a result of the increased use of arachidonic acid for producing prostaglandins and/or leukotrienes. Further understanding of the cause and/or consequence of this finding might lead to a better understanding of prostate cancer.
Long‐term results of nephron‐sparing surgery for renal cell carcinoma in 114 patients: risk factors for progressive disease
Authors: Zigeuner R. , Quehenberger F. , Pummer K. , Petritsch P. , Hubmer G.
Published: September 2003

OBJECTIVES

To evaluate risk factors for metastatic disease after nephron‐sparing surgery (NSS) for renal cell carcinoma (RCC).

PATIENTS AND METHODS

NSS for RCC was used 117 times in 114 patients at our institution; 61 had a normal contralateral kidney and were selected for elective NSS, and in 56 cases (53 patients) the indication for NSS was imperative. Univariate and multiple regression analysis was used to evaluate the risk factors for metastatic disease.

RESULTS

After a mean follow‐up of 80 months, there was tumour progression in 17 of the 114 patients (15%). In the univariate analysis, the tumour diameter (P = 0.03) and imperative indication (P = 0.009), and in multiple regression analysis only imperative indication, were significant risk factors for metastatic disease (P = 0.016).

CONCLUSIONS

Elective NSS for RCC provides excellent long‐term results in selected patients, whereas those undergoing NSS imperatively are at a significantly higher risk of metastatic disease and require a close follow‐up.
Long‐term outcome of bladder papillary urothelial neoplasms of low malignant potential
Authors: Fujii Y. , Kawakami S. , Koga F. , Nemoto T. , Kihara K.
Published: September 2003

OBJECTIVE

To evaluate the long‐term outcome of bladder papillary urothelial neoplasms of low malignant potential (PUNLMP).

PATIENTS AND METHODS

Of 475 consecutive patients with newly diagnosed bladder tumours between 1976 and 1993, 330 (69%) had superficial (Ta and T1) tumours and 53 (11%) were diagnosed as having PUNLMP. Fifty patients (mean age at presentation 57.2 years, range 26–83; male‐to‐female ratio 6 : 1) who were followed for> 5 years or until they died, were included in the present study. All histological slides were reviewed, and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system.

RESULTS

The mean (median, range) follow‐up was 11.7 (10.8, 1.3–24.4) years. During the follow‐up, 30 patients (60%) had local recurrences. The 2, 5 and 10‐year recurrence‐free rates were 66%, 51% and 36%, respectively. No patients developed high‐grade or muscle‐invasive (≥ T2) carcinomas, or upper urinary tract tumours, or died from the disease. At the last follow‐up, 34 patients (68%) had been disease‐free for> 5 years.

CONCLUSIONS

Despite a high recurrence rate, PUNLMP carries a very low malignant potential. We agree with the use of the term ‘papillary urothelial neoplasms of low malignant potential’ instead of ‘superficial bladder carcinoma (cancer)’ for these tumours.
A comparison of aspiration and sclerotherapy with laparoscopic de‐roofing in the management of symptomatic simple renal cysts
Authors: Okeke A.A. , Mitchelmore A.E. , Keeley F.X. , Timoney A.G.
Published: September 2003

OBJECTIVES

To present the results of a minimally invasive treatment of symptomatic simple renal cysts, and to propose an algorithm for their management.

PATIENTS AND METHODS

Seventeen patients presenting with suspected symptomatic simple renal cysts were referred for trial aspiration; 16 presented with loin pain and one with a flank mass. If the cyst and symptoms recurred after a temporary response, they were managed by re‐aspiration with sclerotherapy using 95% ethanol, or by laparoscopic de‐roofing of the cyst.

RESULTS

Of the 17 patients referred, one failed to respond to aspiration and was excluded from further analysis. Three patients had sustained pain relief from simple aspiration alone, 13 required further treatment for symptom relapse, of whom six had aspiration and sclerotherapy, and seven had laparoscopic de‐roofing. After a mean follow‐up of 17 months, pain had recurred in all five patients originally presenting with pain and managed by sclerotherapy, and the patient who presented with a painless mass from a large cyst also developed pain after sclerotherapy. In contrast, the subsequent seven patients managed by laparoscopic treatment are pain‐free at a mean follow‐up of 17.7 months.

CONCLUSION

Evaluation including a diagnostic aspiration is essential to diagnose a symptomatic cyst. When treatment is indicated, laparoscopic de‐roofing appears to be more effective than sclerotherapy.
National and international variation in the registration of bladder cancer
Authors: Crow P. , Ritchie A.W.S.
Published: September 2003

OBJECTIVE

To determine whether variations exist in the methods by which different cancer registries record information on bladder cancers.

METHODS

The registration practices of the various cancer registries within the UK, Europe and the USA were investigated by consulting the available publications and by correspondence with registry staff. In addition, a telephone survey was carried out within the UK to determine whether the national guidelines on bladder cancer coding were being followed.

RESULTS

There is variation in the registration of bladder cancers both among regions within the UK and between the UK and other regions. The telephone survey showed that only four of the 11 UK regional registries were correctly following the national bladder cancer coding guidelines. Bladder cancer registration also varies between the cancer registries within mainland Europe. When comparing registration practices in the UK and the USA the major difference is that cases of bladder carcinoma in situ and pTa transitional cell carcinoma are included in the North American cancer statistics but not in the British cancer statistics.

CONCLUSION

Much needs to be done before it can be claimed that the registration of bladder cancers has been standardized either nationally or internationally. In particular, the differences in registration practices between the UK and the USA will tend to give a falsely low impression of British incidence and survival rates compared with the equivalent North American figures. This confounding factor must be considered if these incidence and survival values are to be compared.
The catheterized patient undergoing transurethral resection of the prostate: a survey of the current practice of British urologists
Authors: Wilson J.R. , Puri R. , Prescott S. , Urwin G.H.
Published: September 2003

OBJECTIVE

To determine, using a postal questionnaire survey of practising British consultant urologists, the duration and type of antibiotic deemed most effective in patients with an existing indwelling catheter before transurethral resection of the prostate (TURP), as the value of prophylactic antibiotics before TURP is well recognized, but no data are available.

METHODS

A questionnaire was posted to each of the 321 practising consultant urologists listed in the handbook of the British Association of Urological Surgeons (1998). A hypothetical situation in the opening statement proposed ‘a patient with an indwelling catheter is to undergo TURP’. The type, timing and duration of prophylactic antibiotic usage were elicited by circling the appropriate response from a choice of several possibilities.

RESULTS

In all, 250 questionnaires were returned; 98% of respondents recognized the importance of the prophylactic use of antibiotics in catheterized patients undergoing TURP, and routinely use them. Most urologists (53%) use more than one dose, with most of these preferring a second dose on catheter removal (60%).

CONCLUSION

The magnitude and diversity of response suggests uncertainty about the appropriate prophylaxis in such patients, and the need for further studies to clarify this situation.
Impalpable testis cancer
Authors: Hindley R.G. , Chandra A. , Saunders A. , O'Brien T.S.
Published: September 2003

OBJECTIVE

To assess the significance of ultrasonographically detected hypoechoic lesions of the testis when the clinical examination is normal, and to highlight the management difficulties thereafter.

PATIENTS AND METHODS

Over a 2‐year period four patients underwent radical orchidectomy where the sole indication for surgery was a hypoechoic lesion detected on ultrasonography (US). The indications for US were persistent scrotal discomfort in two men, contralateral orchitis, and the follow‐up of testicular microlithiasis. The lesions were 4–11 mm in size and one man had several. None of the lesions were palpable; the tumour markers were normal in all patients.

RESULTS

Three of the testes contained seminoma; in one there were two foci of seminoma and in all intratubular germ cell neoplasia was also identified. The remaining case was a Leydig‐cell tumour. All tumours were staged as pT1 after radical inguinal orchidectomy.

CONCLUSION

Impalpable lesions of the testis are likely to be malignant if they are hypoechoic on US and should be considered as seminoma until proved otherwise. The management thereafter is not straightforward, but must ensure an adequate histological diagnosis if the US appearances do not resolve.
Neuroanatomy of the male urethra and perineum
Authors: Yucel S. , Baskin L.S.
Published: September 2003

OBJECTIVE

To describe the topography of the perineal nerves from their pudendal origin to their course into the male genitalia, with specific attention on the course of the perineal nerve along the ventral penis, including branches into bulbospongiosus muscle and corpus spongiosum.

MATERIALS AND METHODS

The study comprised 18 normal human fetal penile specimens at 17.5–38 weeks of gestation (determined by fetal heel‐to‐toe length). Specimens were fixed in formalin, embedded in paraffin wax and serially sectioned at 6 µm. The penile specimens contained the whole penis from the glans to the crural bodies, beneath the pubic arch and the perineum up to the anal verge. Immunocytochemistry was assessed on selected sections with antibodies against the neuronal markers S‐100 and nitric oxide synthase (nNOS). Three‐dimensional computer reconstruction of serial sections allowed an in‐depth analysis of the neuroanatomy of the fetal penis, perineum and surrounding structures.

RESULTS

After the pudendal nerve leaves the pudendal canal it gives rise to the perineal nerve branches in the ischiorectal fossa. Perineal nerves travel alongside the ischiocavernous and bulbospongiosus muscles and before reaching the latter, nerve branches course into the bulbospongiosus muscle. During its pathway within this muscle, fine nerve fibres course into the corpus spongiosum by piercing through the junction of the muscle. At the penoscrotal area, the perineal nerves give branches to the scrotum, funnelling into the interscrotal septum. Perineal nerves continue their pathway over the ventral side of penis covering the ventral surface of corpus spongiosum. Branches of the dorsal nerve of the penis at the junction of corpus cavernosum and corpus spongiosum assemble into a network with the perineal nerves. All perineal nerves from their main trunk at the ischiorectal fossa until their interaction with dorsal nerve of penis at the base of penis were nNOS negative. After the interaction with the dorsal nerve of penis, they become nNOS positive.

CONCLUSION

Integrating neuroanatomical knowledge about the perineal nerves and their communication with the dorsal nerve of penis should facilitate a strategic approach to reconstructive procedures on the penis. Special care should be taken at the junction between the corpora cavernosa and spongiosa, where the dorsal nerve joins the perineal nerve, and at the proximal bulbospongiosus muscle, thereby protecting the fine nerves piercing into the cavernosa spongiosa.
Individual patient variation and inter‐rater reliability of lower calyceal infundibular width on routine intravenous pyelography
Authors: Pace K.T. , Weir M.J. , Harju M. , Tariq N. , D’A.Honey R.J.
Published: September 2003

Three papers in this section all relate, directly or indirectly, to minimally invasive procedures. When John Wickham coined this phrase several years ago, it was not possible to predict how widely used it would become, and how relevant to the future not only of urology, but of surgery in general. Obviously, minimally invasive techniques are not only used in the upper urinary tract, but also in most other parts of the urinary tract. There have been many advances in recent years, but we acknowledge John Wickham as a very important founding father.

OBJECTIVE

To standardise infundibular width (IFW) measurement, to determine patient variability, and to determine inter‐rater variability on intravenous pyelography (IVP).

PATIENTS AND METHODS

Fifty outpatient IVP films were randomly drawn from two hospitals between 1 July 1998 and 31 August 1999, and examined to measure the lower calyceal IFW on the 5, 10 and 20 min films with compression, and after voiding. Kidneys with previous renal surgery, hydronephrosis or renal anatomical anomalies were excluded; in all, 81 kidneys from 50 patients were examined. The IFW was measured at the narrowest point along the infundibulum. All 50 films were then reviewed by two urologists unaware of their origin, to determine the inter‐rater reliability of the infundibular measurements.

RESULTS

Analysis of variance (anova) with posthoc analysis showed a significant difference in IFW at each phase of the IVP (repeated measures anova, P < 0.001). The mean (95% confidence interval) IFW was greatest on the compression film, at 4.4 (2.6) mm, and least on the postvoid film, at 1.6 (2.1) mm. Overall inter‐rater reliability was 0.9780 (intraclass correlation coefficient), and the Pearson correlation between each rater for the IFW at each phase of the IVP was ≥ 0.886.

CONCLUSIONS

There is wide variability in lower calyceal IFW among the various IVP films in a given study. Thus any predictive value of the IFW must be standardized for the timing and IVP film type (compression, postvoid, etc.). The inter‐rater reliability of IFW is high, suggesting that if used correctly it may be more useful in predicting the outcome after shock wave lithotripsy.
Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?
Authors: Staehr P. , Hojlund K. , Hother‐Nielsen O. , Holst J. J. , Beck‐Nielsen H.
Published: September 2003

Aims  In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high‐dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low‐dose insulin infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action.

Methods  We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (– ON) prior overnight insulin infusion. Glucose turnover rates were quantified by adjusted primed‐constant 3‐3H‐glucose infusions, and insulin action was assessed in 4‐h euglycaemic, hyperinsulinaemic (40 mU m−2 min−1) clamp studies using labelled glucose infusates (Hot‐GINF).

Results  Basal plasma glucose levels (mean ± sd) were 5.5 ± 0.5 and 10.7 ± 2.9 mmol/l in the + ON and – ON studies, respectively, and were clamped at −5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and – ON studies, 83 ± 13 vs. 85 ± 14 mg m−2 min−1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than in the – ON study, 84 ± 8 vs. 91 ± 11 mg m−2 min−1 (P = 0.02). During insulin infusion in the clamp period, rates of GP, 23 ± 11 vs. 25 ± 10 mg m−2 min−1, as well as rates of Rd, 133 ± 32 vs. 139 ± 37 mg m−2 min−1, were similar in the + ON and – ON studies, respectively (NS).

Conclusions  Apart from basal rates of Rd, assessment of glucose turnover rates in euglycaemic clamp studies of Type 2 diabetic patients is not dependent on the method by which plasma glucose levels are lowered.
Are analogue insulins better than soluble in continuous subcutaneous insulin infusion? Results of a meta‐analysis
Authors: Colquitt J. , Royle P. , Waugh N.
Published: September 2003

Aims  The properties of rapid‐acting insulin analogues are thought to be particularly appropriate for use in continuous subcutaneous insulin infusion (CSII) or insulin pump therapy. We conducted a systematic review and meta‐analysis of trials comparing rapid‐acting insulin analogues with soluble insulin in CSII.

Methods  The following databases were searched (last search June 2002): MEDLINE 1985–2002; Embase 1980–2002; PubMed internet version, records added June 2001 to June 2002; Science Citation Index 1990–2002; BIOSIS 1999–2002; Web of Science Proceedings 1990–2002; and the Cochrane Library, including DARE and the HTA databases. Randomized controlled trials and crossover studies with at least 10 weeks on each treatment were included. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. A meta‐analysis was undertaken using a random effects model.

Results  A significant improvement of 0.26% (95% confidence interval −0.47, −0.06%) in glycated haemoglobin was demonstrated with lispro. Some studies reported fewer hypoglycaemic episodes with analogue insulin but this varied according to the definitions used. No differences in insulin dosage or weight were seen. Two studies reported patient preference, with analogues preferred in both. The extra cost per annum ranges from £72 (at 40 units per day) to £150 (at 84 units per day).

Conclusions  Insulin analogues result in a modest but significant reduction in HbA1c compared with soluble insulin when used in CSII, and are preferred by patients.
Characteristics of Type 1 diabetes of over 50 years duration (the Golden Years Cohort)
Authors: Bain S. C. , Gill G. V. , Dyer P. H. , Jones A. F. , Murphy M. , Jones K. E. , Smyth C. , Barnett A. H.
Published: September 2003

Background  Type 1 diabetes mellitus is associated with high levels of premature morbidity and mortality. Prolonged survival is possible, however, and some patients appear to be protected from the long‐term complications of this condition.

Methods  Diabetes UK awards medals to patients who have had Type 1 diabetes for 50 years or more. By examining medal‐holders, we have established the clinical and biochemical features of a group of 400 subjects (54% male) with Type 1 diabetes of long duration.

Results  Mean age of the subjects was 68.9 years and mean age‐at‐onset of diabetes 13.7 years. Features of long duration diabetes in this cohort include normal body mass (mean BMI 25.0 kg m−2), low insulin dose (mean 0.52 units kg−2) and greatly elevated HDL‐cholesterol (mean 1.84 mmol/l). Mean HbA1c was 7.6% (normal range 3.8–5.0%) and no patient had a normal HbA1c at the time of venesection. As a group, they have long‐lived parents and consume moderate amounts of alcohol. Medical contact has often been sporadic. A significant proportion (29%) were taking anti‐hypertensive medication. Screening for micro‐ and macroalbuminuria was positive in 35.7%.

Conclusions  Patients with long‐duration (> 50 years) Type 1 diabetes are relatively protected from clinical diabetic nephropathy and large vessel disease; our data are consistent with protection possibly being genetically determined in part via elevated HDL‐cholesterol levels. An abnormal urinary albumin/creatinine ratio is common in these patients, despite their low risk of significant renal deterioration; this may have implications for microalbuminuria screening programmes.
Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene
Authors: Owen Katharine R. , Donohoe Mollie , Ellard Sian , Hattersley Andrew T.
Published: September 2003

Background  Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome.

Case report  We report a 24‐year‐old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin‐fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow‐up period.

Conclusion  This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.
Migraine and Asthma in Childhood: Evidence for Specific Asymmetric Parent-Child Interactions in Migraine and Asthma Families
Authors: Siniatchkin M , Kirsch E , Arslan S , Stegemann S , Gerber W-D , Stephani U
Published: September 2003

In spite of the fact that migraine often manifests as a familial disorder, the role of the family in migraine has not been adequately explored. In this study parent-child interactions in 20 families with a child suffering from migraine were analysed and compared with 20 healthy families and 20 families with an asthma child. The families had to solve a puzzle within a limited time. Parent-child interactions within migraine and asthma families were asymmetric, revealing a disease-specific interpersonal context in the family. Communication with the affected child in migraine families was significantly more directive, with more specific instructions and less help, towards migraineurs than with the healthy siblings. Dominance of parents and submissive behaviour of children were the main features of interactions. In asthma families interactions were more conflicting and less cooperative. This study demonstrated a specific, asymmetric, pattern of family interactions predisposing children either to migraine or asthma.
5-HT1B/1D Serotonin Receptor Agonist Attenuates Nitroglycerin-Evoked Nitric Oxide Synthase Expression in Trigeminal Pathway
Authors: Suwattanasophon C , Phansuwan-Pujito P , Srikiatkhachorn A
Published: September 2003

This study was conducted to investigate the effect of 5-HT1B/1D receptor activation on nitroglycerin (NTG)-induced cerebral hyperaemia and neuronal nitric oxide synthase (nNOS) expression in trigeminovascular neurones. NTG (10 mg/kg) was infused intravenously to adult male Wistar rats with or without pretreatment with 5-HT1B/1D receptor agonist, sumatriptan (0.4 mg/kg, intravenously). Cortical blood flow and expression of nNOS enzyme in trigeminal ganglia, trigeminal nucleus caudalis and perivascular nerve fibre surrounding superior sagittal sinus were measured. The results showed that pretreatment with sumatriptan could significantly shorten the period of NTG-induced cerebral hyperaemia without compromising the magnitude of hyperaemic peak. Sumatriptan pretreatment also attenuated the NTG-evoked expression of nNOS in all studied areas. Based on these findings, we suggest that 5-HT1B/1D receptor has an important role in stabilizing the trigeminovascular system by attenuating the expression of nNOS enzyme, hence reducing nitric oxide production.
Exertional Headache – II. Clinical Features Vaga Study of Headache Epidemiology
Authors: Sjaastad O , Bakketeig LS
Published: September 2003

In connection with a large-scale study of headache epidemiology in the parish of Vågå, Norway ( n = 1838), a prevalence of exertional headache (EH) of 12.3% was recently reported ( n = 202). The principal aim of the present report is to have a closer look at various clinical features: particular attention has been given to the coexistence of EH and migraine. EH seemed to coexist with migraine in 46% of the cases. In spite of that finding, there was generally no plentitude of ‘migraine features’ in the EH attacks per se. The predominant ‘migraine feature’ in EH attacks was throbbing. EH attacks were generally more short-lasting and seemed to be more lenient than the corresponding migraine attacks. Nausea/vomiting, and unilaterality of pain were generally not inherent features of EH attacks. EH attacks in all probability are not abortive migraine attacks – rather, they seem to be ‘migraine-like’.
Patients' Decision-Making for Migraine and Chronic Daily Headache Management. A Qualitative Study
Authors: Peters M , Huijer Abu-Saad H , Vydelingum V , Dowson A , Murphy M
Published: September 2003

The objective of this study was to gain insight into the patients' decision-making for migraine and chronic daily headache management. Patients were recruited by theoretical sampling in Surrey (UK). Semi-structured and tape-recorded interviews ( n = 13) were conducted, transcribed verbatim, coded and analysed according to the grounded theory methodology. Thirteen patients (8 migraine and 5 chronic daily headache) described their management. All patients employed multiple behaviours to manage their headaches. From the patients' descriptions emerged their decision-making. Based on experience, perceptions and new information, the decision-making process involved four stages: headache severity, evaluation, decision making and behaviours. Although the participants were passive with regards to certain management strategies, overall they were actively involved in treating and preventing their headaches. Furthermore, they were active decision-makers in choosing appropriate management. Migraine and chronic daily headache patients are actively involved in managing their headaches. They are key decision-makers and should not be overlooked as a resource for effective management.
Magnetic Resonance Imaging of Patients with Cervicogenic Headache
Authors: Coskun O , Ucler S , Karakurum B , Atasoy HT , Yildirim T , Ozkan S , Inan LE
Published: September 2003

Cervicogenic headache (CH) is a syndrome which is postulated to originate from nociceptive structures in the neck or head. The anatomical neck or head structures that are responsible for the pain in CH have not been clearly identified, but the pain in these patients probably originates from the structures of the cervical spine. In this study, cervical MRI were studied in 22 patients with cervicogenic headache and 20 control patients who did not have any disease which may effect the bone and muscle structures of cervical region. MRI imaging of cervical vertebra showed a disc bulging in 10 (45.4%) out of 22 patients with CH and in 9 (45.0%) of 20 controls ( P > 0.05). The distribution of pathological lesions in patients and controls were not significantly different ( P > 0.05). As a result, MRI may not be an adequate method to detect pathological findings underlying the aetiology of CH such as nerve roots, intervertebral joints and periosteum.
Brain‐derived neurotrophic factor shows a protective effect and improves recovery of the ERG b‐wave response in light‐damage
Authors: Ikeda Kazuhito , Tanihara Hidenobu , Tatsuno Tohru , Noguchi Hiroshi , Nakayama Chikao
Published: September 2003

We investigated the neuroprotective effects of brain‐derived neurotrophic factor (BDNF) and its influence on the functional recovery of the retina following light‐induced retinal damage by electroretinogram (ERG). Rats were exposed to constant fluorescent light for 2, 5, 7, or 14 days, then returned to a cyclic light environment for 14 days. The result indicated that BDNF had few effects on the a‐wave amplitude, but there was a statistically significant difference in the b‐wave amplitudes between BDNF‐treated and control eyes from day 0–14 of the recovery period following 2 days of light exposure (p < 0.05). Our findings suggest that BDNF not only protects the retinal neuronal function but also enhances the recovery from retinal light damage.
Nitric oxide and Fenton/Haber–Weiss chemistry: nitric oxide is a potent antioxidant at physiological concentrations
Authors: Sharpe Martyn A. , Robb Sarah J. , Clark John B.
Published: September 2003

We have examined the action of nitric oxide (NO) on the ability of Fenton's reagent (ferrous iron and hydrogen peroxide), to oxidize a number of organic optical probes. We found that NO is able to arrest the oxidation of organic compounds at concentrations of NO found in brain, in vivo. We present evidence that Fenton's reagent proceeds via a ferryl intermediate ([Fe=O]2+), before the generation of hydroxyl radical ·(OH). NO reacts rapidly with this ferryl, blocking the production of ·OH. We propose that NO has an important role in protecting biological tissues, and the brain in particular, from Fenton chemistry.
Uncoupling protein 2 influences dopamine secretion in PC12h cells
Authors: Yamada Shigeru , Isojima Yasushi , Yamatodani Atsushi , Nagai Katsuya
Published: September 2003

Uncoupling protein 2 (UCP2) belongs to the UCP family, and is distributed in many organs including the brain. Although UCP2 is known to be related to many functions such as the regulation of insulin secretion or the scavenging of the radicals, the role of UCP2 in the central nervous system remains unclear. In this report, rat UCP2 (rUCP2) and its mutants were overexpressed in the PC12h cells to determine the physiological roles played by UCP2 in neural cells and to elucidate the mechanisms that regulate these functions. It was found that rUCP2 was activated by the stimulation of the cAMP‐protein kinase A (PKA) cascade. Moreover, the activation of rUCP2 suppressed intracellular ATP levels and inhibited the cAMP‐dependent increase of dopamine secretion. Thus, UCP2 appears to be regulated by the excitatory stimulus via the cAMP‐PKA cascade and serves to negatively control the synaptic output by reducing intracellular ATP levels.
Increased dopamine and its metabolites in SH‐SY5Y neuroblastoma cells that express tyrosinase
Authors: Hasegawa Takafumi , Matsuzaki Michiko , Takeda Atsushi , Kikuchi Akio , Furukawa Katsutoshi , Shibahara Shigeki , Itoyama Yasuto
Published: September 2003

Oxidized metabolites of dopamine, known as dopamine quinone derivatives, are thought to play a pivotal role in the degeneration of dopaminergic neurons. Although such quinone derivatives are usually produced via the autoxidation of catecholamines, tyrosinase, which is a key enzyme in melanin biosynthesis via the production of DOPA and subsequent molecules, may potentially accelerate the induction of catecholamine quinone derivatives by its oxidase activity. In the present study, we developed neuronal cell lines in which the expression of human tyrosinase was inducible. Overexpression of tyrosinase in cultured cell lines resulted in (i) increased intracellular dopamine content; (ii) induction of oxidase activity not only for DOPA but also for dopamine; (iii) formation of melanin pigments in cell soma; and (iv) increased intracellular reactive oxygen species. Interestingly, the expressed tyrosinase protein was initially distributed in the entire cytoplasm and then accumulated to form catecholamine‐positive granular structures by 3 days after the induction. The granular structures consisted of numerous rounded, dark bodies of melanin pigments and were largely coincident with the distribution of lysosomes. This cellular model that exhibits increased dopamine production will provide a useful tool for detailed analyses of the potentially noxious effects of oxidized catecholamine metabolites.
The new neurokinin 1‐sensitive receptor mediates the facilitation by endogenous tachykinins of the NMDA‐evoked release of acetylcholine after suppression of dopaminergic transmission in the matrix of the rat striatum
Authors: Kemel Marie‐Louise , Pérez Sylvie , Beaujouan Jean‐Claude , Jabourian Maritza , Soubrié Philippe , Glowinski Jacques
Published: September 2003

Using an in vitro microsuperfusion procedure, the NMDA‐evoked release of [3H]ACh was studied after suppression of dopamine (DA) transmission (α‐methyl‐p‐tyrosine) in striatal compartments of the rat. The effects of tachykinin neurokinin 1 (NK1) receptor antagonists and the ability of appropriate agonists to counteract the antagonist responses were investigated to determine whether tachykinin NK1 classic, septide‐sensitive and/or new NK1‐sensitive receptors mediate these regulations. The NK1 antagonists, SR140333, SSR240600, GR205171 but not GR82334 and RP67580 (0.1 and 1 µm) markedly reduced the NMDA (1 mm + d‐serine 10 µm)‐evoked release of [3H]ACh only in the matrix. These responses unchanged by coapplication with NMDA of NK2 or NK3 agonists, [Lys5,MeLeu9,Nle10]NKA(4–10) or senktide, respectively, were completely counteracted by the selective NK1 agonist, [Pro9]substance P but also by neurokinin A and neuropeptide K (1 nm each). According to the rank order of potency of agonists for counteracting the antagonist responses ([Pro9]substance P, 0.013 nm > neurokinin A, 0.15 nm ≫ substance P(6–11) 7.7 nm = septide 8.7 nm), the new NK1‐sensitive receptors mediate the facilitation by endogenous tachykinins of the NMDA‐evoked release of ACh in the matrix, after suppression of DA transmission. Solely the NK1 antagonists having a high affinity for these receptors could be used as indirect anti‐cholinergic agents.
Induction of an interferon‐γ Stat3 response in nerve cells by pre‐treatment with gp130 cytokines
Authors: Kaur Navjot , Kim In‐Jung , Higgins Dennis , Halvorsen Stanley W.
Published: September 2003

Many cytokines mediate their effects through Jak/STAT signaling pathways providing many opportunities for cross‐talk between different cytokines. We examined the interaction between two cytokine families, gp130‐related cytokines and interferon‐γ (IFN‐γ), which are coexpressed in the nervous system during acute trauma and pathological conditions. Typical nerve cells show an IFN‐γ response that is restricted to activating STAT1, with minor activation of STAT3. IFN‐γ elicited a pronounced STAT3 response in cells pre‐treated for 5–7 h with ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or interleukin‐6. CNTF or interleukin‐6 induced an IFN‐γ STAT3 response in a variety of cells including SH‐SY5Y human neuroblastoma, HMN‐1 murine motor neuron hybrid cells, rat sympathetic neurons and human hepatoma HepG2 cells. The enhancement was measured as an increase in tyrosine phosphorylated STAT3, in STAT3‐DNA binding and in STAT‐luciferase reporter gene activity. The enhanced STAT3 response was not due to an increase in overall STAT3 levels but was dependent upon ongoing protein synthesis. The induction by CNTF was inhibited by the protein kinase C inhibitor, BIM, and the MAPK‐kinase inhibitor, U0126. Further, H‐35 hepatoma cells expressing gp130 receptor chimeras lacking either the SHP‐2 docking site or the Box 3 STAT binding sites failed to enhance the IFN‐γ STAT3 response. These results provide evidence for an interaction between gp130 and IFN‐γ cytokines that can significantly alter the final cellular response to IFN‐γ.
Activation of muscarinic cholinergic receptors enhances the volume‐sensitive efflux of myo‐inositol from SH‐SY5Y neuroblastoma cells
Authors: Loveday Danny , Heacock Anne M. , Fisher Stephen K.
Published: September 2003

A mechanism used by cells to regulate their volume under hypo‐osmotic conditions is the release of organic osmolytes, one of which is myo‐inositol. The possibility that activation of phospholipase‐C‐linked receptors can regulate this process has been examined for SH‐SY5Y neuroblastoma cells. Incubation of cells with hypo‐osmolar buffers (160–250 mOsm) led to a biphasic release of inositol which persisted for up to 4 h and could be inhibited by inclusion of anion channel blockers – results which indicate the involvement of a volume‐sensitive organic anion channel. Inclusion of oxotremorine‐M, a muscarinic cholinergic agonist, resulted in a marked increase (80–100%) in inositol efflux under hypo‐osmotic, but not isotonic, conditions. This enhanced release, which was observed under all conditions of hypo‐osmolarity tested, could be prevented by inclusion of atropine. Incubation of the cells with either the calcium ionophore, ionomycin, or the phorbol ester, phorbol 12‐myristate 13‐acetate, partially mimicked the stimulatory effect of muscarinic receptor activation when added singly, and fully when added together. The ability of oxotremorine‐M to facilitate inositol release was inhibited by removal of extracellular calcium, depletion of intracellular calcium or down‐regulation of protein kinase C. These results indicate that activation of muscarinic cholinergic receptors can regulate osmolyte release in this cell line.
Presynaptic regulation of dopaminergic neurotransmission
Authors: Schmitz Yvonne , Benoit‐Marand Marianne , Gonon François , Sulzer David
Published: September 2003

The development of electrochemical recordings with small carbon‐fiber electrodes has significantly advanced the understanding of the regulation of catecholamine transmission in various brain areas. Recordings in vivo or in slice preparations monitor diffusion of catecholamine following stimulated synaptic release into the surrounding tissue. This synaptic ‘overflow’ is defined by the amount of release, by the activity of reuptake, and by the diffusion parameters in brain tissue. Such studies have elucidated the complex regulation of catecholamine release and uptake, and how psychostimulants and anti‐psychotic drugs interfere with it. Moreover, recordings with carbon‐fiber electrodes from cultured neurons have provided analysis of catecholamine release and its plasticity at the quantal level.
Hunting‐Related Changes in Game Encounter Rates from 1994 to 2001 in the Mbaracayu Reserve, Paraguay
Authors: Hill Kim , McMillan Garnett , Fariña Rosalia
Published: September 2003

Abstract: This longitudinal study examines the impact of native hunting on the populations of 10 important game species in the Mbaracayu Reserve, Paraguay. From July 1994 to July 2001, native Ache research assistants surveyed 7,535 km of diurnal random transects in the reserve. Analyses of data from these transects and harvest‐ rate data from 5,526 Ache hunter days suggest that the hunting return rate declined significantly for one species. Nonsignificant declines were observed for 6 of the other 9 species. Native harvest percentages of the stock population appear sustainable for 10 major prey species, but rates of harvest from nonindigenous poaching could not be determined. Crude encounter rates for all 10 species declined over time, but only 2 of these were statistically significant in a univariate model. Multivariate logistic regression controlling for habitat type and location in the reserve showed significant declines in encounter rates over time for 4 species, but the effect of interaction between time and hunting pressure failed to confirm that declines in encounter rates were steeper in more‐hunted versus less‐hunted areas of the reserve. This may mean that other factors unrelated to hunting pressure are responsible for some of the declines in game encounter rates.
Impacts of the Brown Tree Snake: Patterns of Decline and Species Persistence in Guam's Avifauna
Authors: Wiles Gary J. , Bart Jonathan , Beck Robert E. , Aguon Celestino F.
Published: September 2003

Abstract: Predation by brown tree snakes (   Boiga irregularis ) devastated the avifauna of Guam in the Mariana Islands during the last half of the twentieth century, causing the extirpation or serious reduction of most of the island's 25 resident bird species. Past studies have provided qualitative descriptions of the decline of native forest birds but have not considered all species or presented quantitative analyses. We analyzed two sets of survey data gathered in northern Guam between 1976 and 1998 and reviewed unpublished sources to provide a comprehensive account of the impact of brown tree snakes on the island's birds. Our results indicate that 22 species, including 17 of 18 native species, were severely affected by snakes. Twelve species were likely extirpated as breeding residents on the main island, 8 others experienced declines of ≥90% throughout the island or at least in the north, and 2 were kept at reduced population levels during all or much of the study. Declines of ≥90% occurred rapidly, averaging just 8.9 years along three roadside survey routes combined and 1.6 years at a 100‐ha forested study site. Declines in northern Guam were also relatively synchronous and occurred from about 1976 to 1986 for most species. The most important factor predisposing a species to coexistence with brown tree snakes was its ability to nest and roost at locations where snakes were uncommon. Large clutch size and large body size were also related to longer persistence times, although large body size appeared to delay, but not prevent, extirpation. Our results draw attention to the enormous detrimental impact that brown tree snakes are likely to have upon invading new areas. Increased containment efforts on Guam are needed to prevent further colonizations, but a variety of additional management efforts would also benefit the island's remaining bird populations.