bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological assessment of epithelial function in damaged rat colon
Authors: Kumagai  , Tomioka  , Hayashi
Published: March 2003

Objective

To assess colonic damage quantitatively by electrophysiological parameters such as membrane potential difference, short circuit current and transepithelial resistance, and by colonic membrane permeability (permeation clearance) of FITC‐labelled dextran 4000.

Materials and methods

For experimental colitis models of rats, trinitrobenzene sulphonic acid‐, acetic acid‐, and dextran sulphate sodium‐induced models were employed. The Ussing‐type chamber was used for determination of the electrophysiological parameters and permeation clearance of FITC‐labelled dextran 4000.

Results

Reductions of all the above electrophysiological parameters were observed in trinitrobenzene sulphonic acid‐ and acetic acid‐induced models. No good correlation between the reduction in the parameters and the intestinal damage score was found in any of the models. This shows that damage scores do not necessarily reflect precise changes in physiological epithelial function. In contrast, the electrophysiological parameters were well correlated with membrane permeability. The reduction in transepithelial resistance, i.e. reduction in barrier function, was supported by an increase in permeation clearance of FITC‐labelled dextran 4000 and the plasma appearance of endotoxin in the trinitrobenzene sulphonic acid‐induced model. Through the recovery of transepithelial resistance and permeation clearance of FITC‐labelled dextran 4000 to control values in the acetic acid‐induced model, automatic recovery of the model to normal occurred.

Conclusion

Examination of the electrophysiological parameters and permeation clearance of FITC‐labelled dextran 4000 can provide a useful method of assessment of epithelial damage.
Perineal wound morbidity following proctectomy for inflammatory bowel disease (IBD)
Authors: Adam  , Shorthouse
Published: March 2003

Objective

Delayed perineal wound healing following ‘conventional’ excision of the rectum for IBD is common—up to 58% in patients with ulcerative colitis (UC) and 72% in those with Crohn’s disease (CD) 6 months following proctectomy. The risk of perineal wound morbidity is increased if anorectal sepsis is present at the time of proctectomy. The aim of this study was to establish the incidence of perineal wound sepsis in a consecutive series of patients treated by close rectal and intersphincteric anal canal dissection to preserve the pelvic floor and suction drainage to minimize the residual pelvic dead space.

Patients and methods

Anorectal sepsis if present was drained preoperatively. Omental transposition was used selectively to occlude residual cavities after fistula tracks had been laid open. Between 1989 and 1996, 46 patients (median age 56 years) underwent rectal excision, 27 for UC and 19 for CD. In seven patients the faecal stream was diverted at least 2 months prior to proctectomy. In all but five patients primary closure of the perineum was carried out (89.1%).

Results

Uncomplicated wound healing occurred in 37/46 (80.4%) patients. All patients in whom the perineum was left open healed within 6 months without subsequent chronic sinus formation. At a median follow up of 3.4 years (2.1–7.4 years), no patient with UC had further perineal wound problems and only 2/19 (10.5%) of CD patients had a persistent chronic perineal sinus. Preoperative faecal diversion had no influence on the incidence of subsequent perineal wound morbidity.

Conclusion

Uncomplicated perineal wound healing after rectal excision for IBD appears more likely to occur after preoperative control of anorectal sepsis, minimizing dead space in the pelvis by perimuscular rectal excision, use of suction drainage, intersphincteric dissection of the anal canal and selective use of omental transposition.
Clinical and physiological heterogeneity in slow transit constipation: a review of 122 patients
Authors: Knowles  , Scott  , Williams  , Lunniss
Published: March 2003

Objective

The outcome of surgery in patients with slow transit constipation (STC) is unpredictable. This may reflect clinical and physiological heterogeneity within this group of patients. This study attempts to identify subgroups of patients with STC according to clinical history, and compares the pathophysiological findings between the two largest: including patients with chronic idiopathic STC, and those with symptoms acquired after pelvic surgery or childbirth (post‐pelvic intervention STC).

Patients and methods

Review of clinical and gastrointestinal pathophysiological findings of 122 consecutive patients with slow colonic transit.

Results

Six subgroups of patients were defined according to the time and nature of onset of symptoms. Pathophysiological comparison of the two main groups: chronic idiopathic STC (n=65 (53%)) and post‐pelvic intervention STC (n=22 (18%)), yielded three main conclusions: (i) the pattern of colonic transit is similar in both groups, i.e. predominantly (approximately 70%) generalized; (ii) the prevalence of a rectal evacuatory disorder is significantly higher in patients with post‐pelvic intervention STC (77% vs 32%, P=0.004); and (iii) small bowel motility disturbances occur in both groups (overall 48%), and are therefore not limited to patients with chronic idiopathic STC.

Conclusion

There are pathophysiological similarities and differences between the main two subgroups of STC. Such findings may help our understanding of the pathogenesis and have implications in the future management of these patients.
Inter‐observer variability in the reporting of dynamic evacuation proctography
Authors: Stojkovic S. G. , Ireland I. W. , Holmfield J. H. , Sagar P. M. , Finan P. J.
Published: March 2003

Objective

To determine the degree of inter‐observer variability between two reporters of dynamic evacuation proctography (DEP).

Patients and methods

The videotapes of 136 patients who had undergone the investigation of DEP in a 1‐year period were retrospectively and independently reported by two of the authors. The authors recorded the presence or absence of an anterior rectocoele (as well as size—small, medium or large), an intussusception, a rectal prolapse and any degree of non‐relaxing puborectalis syndrome (NRPS).

Results

The results were analysed using the κ statistic. I.W.I. reported 18% of the proctograms as normal. S.G.S. reported 26% of the proctograms as normal. κ scores for agreement on the presence or absence of rectal prolapses, NRPS, intussusception and anterior rectocoeles between the two reporters were 0.79, 0.70, 0.54 and 0.82, respectively.

Conclusion

Usefulness of an investigation is dependent upon its reproducibility and hence on the degree of inter‐observer variability in its reporting. Our study shows that DEP is a useful investigation for delineating the mechanics of the pelvic floor and that consistency of reporting in our Department is good.
Comparison of the Moskowitz criteria and the pouchitis disease activity index (PDAI) for diagnosis of ileoanal pouch inflammation
Authors: Evgenikos N. , Bartolo D. C. C. , Hamer‐Hodges D. W. , Ghosh S.
Published: March 2003

Objective

To prospectively compare two indices for diagnosis of pouchitis: Moskowitz criteria and pouchitis disease activity index (PDAI).

Patients and methods

Fifty‐six consecutive patients with an ileoanal pouch for ulcerative colitis were recruited. A clinical questionnaire was composed and the Öresland functional score calculated. Pouchoscopy and biopsy were performed after cleansing of the pouch.

Results

Seven patients had pouchitis according to both Moskowitz and PDAI (‘positive’ group). Five patients had PDAI ≥ 7, but did not fulfil the Moskowitz criteria (‘negative’ group). The pouchoscopy and Öresland functional scores were similar between the two groups. The biopsy neutrophilia and ulceration were more prominent in the ‘positive’ group (χ2=5.18, P < 0.05), whereas urgency (χ2=8.4, P < 0.001), evacuation difficulties (χ2=5.18, P < 0.05) and history of bleeding per pouch (χ2=4.18, P < 0.05) were more pronounced in the ‘negative’ group.

Conclusion

Moskowitz criteria may be broadly in agreement with the PDAI; these, however, cannot be regarded as interchangeable.
Island flap perineoplasty decreases the incidence of wound breakdown following overlapping anterior sphincter repair*
Authors: Draganic B. , Eyers A. A. , Solomon M. J.
Published: March 2003

Objective

Overlapping anterior sphincter repair is the accepted treatment for faecal incontinence resulting from sphincter disruption, however, wound breakdown has been reported to occur in up to 30% of patients. The aim of this study was to assess whether the type of wound closure affected the incidence of wound breakdown, and in particular whether island flap perineoplasty decreased this incidence.

Methods

An historical control study was performed evaluating wound outcomes in patients undergoing different methods of wound closure after sphincter repair. Data were obtained from a prospectively collected database.

Results

85 patients who underwent overlapping sphincter repair were studied. Five patients had their wounds left open to heal by granulation. Of the remaining 80 patients, wound dehiscence occurred in 33 patients (41%). When wound breakdown did occur, the mean time to healing was 9.1 weeks. Wound dehiscence was found to occur significantly less frequently in patients having an island flap perineoplasty than in those having other forms of wound closure (15 vs 54%; P=0.0015). The presence of a complex injury such as cloacal defect or recto‐vaginal fistula was also found to increase the incidence of wound breakdown, however, performing additional operations at the time of sphincter repair such as levator‐plasty, gynaecological procedures or defunctioning colostomy did not affect the incidence of wound disruption.

Conclusions

Wound disruption following overlapping anterior sphincter repair occurs in a significant proportion of patients and results in prolonged healing. Island flap perineoplasty significantly decreases the incidence of wound disruption in comparison to other forms of wound closure.
In vitro and preclinical studies of targeted alpha therapy (TAT) for colorectal cancer
Authors: Rizvi S. M. A. , Allen B. J. , Tian Z. , Goozee G. , Sarkar S.
Published: March 2003

Introduction

Effective targeted cancer therapy requires high selectivity and cytotoxicity of the labelled product. We report the preparation and testing of anticolorectal cancer monoclonal antibody c30.6 radioimmunoconjugates (RIC) labelled with alpha‐emitting Bismuth‐213 and positron emitting Terbium‐152 using two chelators, viz. Cyclic dianhydride of diethylenetriaminepentacetic acid (DTPA) and CHX‐A′′ (a DTPA derivative).

Methods

Selectivity and stability of the RIC were tested in vitro (flow cytometry) and in vivo (biodistribution, organ/tumour uptake and retention). Cytotoxicity assays were carried out using tritiated thymidine uptake (inhibition of DNA synthesis) and MTS assay.

Results

High labelling efficiency (ranging between 89 and 91%) and stability over 2–5 half‐lives of the isotopes were seen. Kidney retention was not seen in contrast to high uptake and retention of both conjugates in tumours. Flow cytometry studies showed high specificity of the antibody before and after labelling and this unchanged targeting behaviour was reflected in cytotoxicity assays. These assays showed that only alpha‐labelled antibody could selectively kill the cancer cells for activities as low as 2–3 μCi. The study also revealed that free isotopes or isotopes bound to nonspecific antibodies did not kill cancer cells.

Conclusion

The stability of the RICs and outstanding cytotoxicity of the alpha emitter, together with no kidney retention and high tumour uptake and retention of the radiolabel, offers a new approach for the potential control of colorectal cancer.
Success and failure after repair of rectovaginal fistula in Crohn’s disease: analysis of prognostic factors
Authors: Penninckx F. , Moneghini D. , D'Hoore A. , Wyndaele J. , Coremans G. , Rutgeerts P.
Published: March 2003

Objective

To compare the healing rate after several types of surgical repair of rectovaginal fistula (RVF) in Crohn’s disease, and to identify factors predicting a successful outcome.

Patients and methods

A Medline review of the literature since 1980 and analysis of our results in 32 consecutive patients was done.

Results

All types of repair (rectal, vaginal, anocutaneous advancement flap, or perineoproctotomy with fistula closure) seem to be equally effective. Healing after a first repair is observed in 58 (46–71)%. Healing can still be obtained at subsequent attempts in 62 (40–71)% of the patients. The reported overall healing rate is 75 (56–93)%. The need for proctectomy after an attempt to repair was 6 (0–27)% in these series. Using a tailored surgical approach, we observed primary healing in 57%, healing after one or more supplementary procedures in 71%, for a total ‘definitive’ closure rate of 75%. Anal continence was never compromised and all temporary stomas (12 patients) could be closed. Univariate analysis identified number of Crohn’s sites, presence of extra‐intestinal disease and previous Crohn’s proctitis to be related with problematic healing after a surgical repair. A positive relation was found between extra‐intestinal disease and the number of repairs needed to ultimately obtain healing, whereas the relation with previous right hemicolectomy was negative. Multivariate analysis revealed the number of Crohn’s sites as the only factor predicting problematic healing. A defunctioning stoma was not related to the healing rate and had its intrinsic morbidity with supplementary hospitalization (9.6 days). After a median follow‐up of 40.4 (range 8–87) months, we observed 4 late recurrences in 25 patients with healed RVF (16%).

Conclusion

Closure of a RVF in Crohn’s disease should not be considered an easy undertaking, especially in patients with several Crohn’s sites. In this very heterogeneous group of patients the technique is adapted to the nature and the extent of accompanying anorectal disease. Construction of a temporary stoma is not mandatory and can be limited to complex cases. Healing can be obtained in 75% of all patients, although a late recurrence might occur.
Assessment and classification of never operated and recurrent cryptoglandular fistulas‐in‐ano using hydrogen peroxide enhanced transanal ultrasound
Authors: Sloots C. E. J. , Felt‐Bersma R. J. F. , Poen A. C. , Cuesta M. A.
Published: March 2003

Objective

Classification and visualization of fistula‐in ano is used to determine surgical treatment according to the type of fistula, predict the recurrence rate and incontinence risk and compare the results of treatment published in literature. Hydrogen peroxide enhanced transanal ultrasound (HPUS) with the peroxide introduced through the external opening of the fistula gives a clear and accurate visualization of the track in relation to the sphincters. The aim of this study was to review never operated and recurrent cryptoglandular fistulas‐in‐ano visualized with the aid of HPUS in order to establish the anatomical differences.

Patients and methods

Eighty‐one patients with never operated (48) or recurrent (33) cryptoglandular fistulas‐in‐ano were assessed by clinical examination and HPUS.

Results

Never operated fistulas were single track, trans‐ or inter‐sphincteric fistulas in 80%. In 15%, the tracks were sinus with no connection to the pectinate line. Two patients (5%) had a transsphincteric fistula with a ramification. No supra‐ or extra‐sphincteric fistulas were found in the never operated fistula group. In the recurrent fistula patients, 57% had a single trans or intersphincteric track, 15% of the patients had a single track supra or extrasphincteric fistula and 27% had a ramified fistula.

Conclusions

All never operated cryptoglandulair fistulas‐in‐ano were inter‐ or trans‐sphincteric. An extra track was found in 5%. Recurrent fistulas‐in‐ano were supra or extrasphincteric in 15% and ramified in 27%. Therefore, never operated fistula‐in‐ano does not require any special investigation before surgical treatment. However, before treating recurrent fistulas, visualization by HPUS is recommended to detect supra or extrasphincteric fistulas or ramification.
Mesorectal excision for rectal cancer: functional outcome after low anterior resection and colorectal anastomosis without a reservoir
Authors: Nesbakken A. , Nygaard K. , Lunde O. C.
Published: March 2003

Objective

The anal sphincters, neorectal capacity and motility may be affected by injury to the autonomic nerves during rectal resection. Anorectal function also depends on the method used for restoration of intestinal continuity, and colonic reservoir reconstruction has been recommended in ultralow anastomosis. This study was undertaken to evaluate the results after nerve preserving mesorectal excision and colorectal anastomosis without a reservoir.

Patients and methods

Thirty‐five consecutive patients who underwent low anterior resection with primary healing of the anastomosis, were included. Anal manometry with stationary pull through technique, rectal volumetry and symptom scoring (written questionnaires with visual analogue scales) were performed prior to and 12 months after surgery. Anal sphincter function was evaluated in all patients, but five patients with a colonic reservoir were excluded from the other evaluations. Thirty patients entered the main study; 14 patients having a total mesorectal excision (TME) and a low anastomosis (LA) (4–6 cm) and 16 patients a partial mesorectal excision (PME) and a high anastomosis (HA) (7–11 cm from the anal verge).

Results

Anal resting and squeeze pressure and rectal sensibility (threshold volume) were unchanged after the operation. The rectal volume eliciting urge to defecate was reduced from median 95 ml to 70 ml (P < 0.01), and the maximum tolerable rectal volume was reduced from 200 to 135 ml (P < 0.01) after the operation. The maximum tolerable volume was significantly lower in patients with LA than in patients with HA (P < 0.01). Overall functional results were good. The patients reported problems with complete bowel emptying (median VAS‐score reduction from 90 to 60, P < 0.01), and minor incontinence problems (median VAS‐score reduction from 100 to 90, P= 0.03). The reduction of VAS‐scores was more pronounced in LA than HA patients (without reaching statistical significance).

Conclusions

Anal sphincter function was preserved after mesorectal excision. Neorectal capacity was reduced, most pronounced in patients with LA. The overall functional results were satisfactory and slightly better in patients with HA than in those with LA.
Femoral nerve injury as a complication of pelvic surgery
Authors: Schofield P. F.
Published: March 2003

Femoral nerve injury is a rare complication of pelvic surgery but may lead to medicolegal actions. The common cause is the use of a long‐bladed self‐retaining pelvic retractor. The injury is not well recognised in coloproctology practice and this brief article is to draw attention to this complication.
Lowering of circulating insulin and leptin is closely associated following weight reduction after vertical banded gastroplasty in obese women
Authors: Guldstrand M. , Backman L. , Adamson U. , Lins P. E. , Ahrén B.
Published: March 2003

Aim: To explore whether the lowering of insulin relates to changes in leptin following weight reduction after vertical banded gastroplasty (VBG) in seven grossly obese women (BMI 45.9 ± 1.5 kg/m2).

Results: At 6–24 months after VBG, BMI was reduced to 31.3 ± 0.9 kg/m2 (p < 0.018), leptin from 43 ± 9 to 12 ± 2 ng/ml (p < 0.018) and insulin from 172 ± 19 to 71 ± 2 pmol/l (p=0.018). The reduction in leptin correlated to the reduction in insulin (r = 0.94, p = 0.002) but not to that of BMI (r = 0.05, NS).

Conclusion: Reduction in insulin seems more important for reduction in leptin than lowering of BMI, suggesting a close association between leptin and insulin in obese subjects.
Insulin resistance: the fundamental trigger of type 2 diabetes
Authors: Groop L. C.
Published: March 2003

Summary. Type 2 diabetes is a heterogeneous condition that is not attributable to a single pathophysiological mechanism. In general, both insulin resistance and impaired insulin secretion are required for the disease to become manifest. Thus, as long as the pancreatic β cells can compensate for the degree of insulin resistance, glucose tolerance remains normal. Clustering of type 2 diabetes in certain families and ethnic populations points to a strong genetic background for the disease. However, environmental factors such as obesity and a sedentary lifestyle are usually required to unmask the genes.
The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome
Authors: Rett K.
Published: March 2003

Summary. It has been known for years that cardiovascular disease frequently precedes the development of type 2 diabetes, and that atherosclerosis might not be a complication of type 2 diabetes, but rather the consequence of common genetic and environmental factors (the ‘common soil’ hypothesis). The insulin resistance syndrome (IRS) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, hyperinsulinaemia, android fat distribution, progressive glucose intolerance, dyslipidaemia (increased triglycerides, decreased HDL, increased small dense LDL), increased prothrombotic and antifibrinolytic factors, and hypertension. Many of these abnormalities are risk factors for type 2 diabetes, and most of them explain the predilection for atherosclerosis to occur in conjunction with IRS. Insulin resistance is a key feature of IRS, and has been suggested to be the common pathophysiological basis of atherosclerosis and type 2 diabetes. The term ‘insulin resistance’ denotes resistance to insulin‐mediated glucose uptake into skeletal muscle, which can be measured by the glucose clamp technique. There are, however, other less understood sites of abnormal insulin action that may also be relevant in IRS. These include liver, adipose, and kidney tissue, and systems such as muscle perfusion, antilipolysis, lipoprotein lipase activity, and cation transport. The development of clinical cardiovascular end‐points in a patient with insulin resistance is complex, as it includes the degree of the defect, its associated abnormalities, its consequences, and the ability to compensate for the underlying defect. It is therefore more appropriate to consider the different facets and risk factors of IRS in aggregate, rather than seeking ‘independent’ effects. Accordingly, treatment of insulin resistance per se has not yet been shown to reduce the incidence of cardiovascular complications. At the cellular level, excess insulin is involved in various elements of atherogenesis. It interacts with cytokines and growth factors in a cross talk among vascular wall cells and a variety of mediators that play a role in the establishment of atheroma. Excess insulin also plays an important role in concert with lipoproteins when they exhibit an abnormal pattern and become modified by oxidation and glycation. It is therefore currently hoped that the introduction of a new class of insulin‐sensitizing agents, the thiazolidinediones, may attenuate these processes. The thiazolidinediones act through ligand activation of a nuclear transcription factor, the peroxisomal proliferator‐activated receptor‐γ (PPARγ). Although this receptor was initially linked to lipid and glucose metabolism, recent data suggest that PPARγ is also involved in the differentiation of mononuclear phagocytes, their inflammatory reactions, and macrophage conversion to foam cells. Thus, PPARγ ligands may also be important regulators of monocyte/macrophage gene expression during atherogenesis.
Short‐term hypothyroidism has no effect on serum leptin concentrations
Authors: Simó R. , Hernández C. , Zafon C. , Galofré P. , Castellanos J. M. , Mesa J.
Published: March 2003

The aim of the study is to determine the effect of short‐term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin‐suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 ± s.e.m. 2.14 vs. 17.6 ± s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short‐term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.
Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic fatty rat
Authors: Smith S. A. , Lister C. A. , Toseland C. D. N. , Buckingham R. E.
Published: March 2003

Summary

Aim  To investigate the potential of rosiglitazone, a highly potent agonist at the nuclear peroxisome proliferator activated receptor‐γ (PPAR‐γ), to prevent the development of diabetes in the Zucker diabetic fatty (ZDF) rat or to ameliorate the condition at a later stage of the disease.

Methods  Rosiglitazone (10 μmol/kg body weight daily) was given via the diet to ZDF rats from aged 6 weeks, before the onset of hyperglycaemia (Prevention group), or from aged 21 weeks after hyperglycaemia and proteinuria were established (Intervention group). Untreated ZDF rats and age‐matched Zucker lean rats (ZL) served as controls and the experiment was terminated when the animals were aged 28 weeks.

Results  Whilst the combined ZDF control and Intervention groups were already hyperglycaemic (14.6 ± 1.6 vs. ZL 5.7 ± 0.1 mmol/l, mean ± s.e.m.; p < 0.05), glycosuric and polydipsic at aged 11 weeks, and thereafter had a declining plasma insulin concentration, rosiglitazone Prevention treatment maintained normoglycaemia even at aged 27 weeks (3.7 ± 0.3 mmol/l vs. ZL 3.0 ± 0.3 mmol/l; NS). Intervention treatment at aged 21 weeks, however, failed to ameliorate the diabetes. These functional data were supported by determinations of pancreatic insulin content (μg/mg tissue as follows: ZL, 43.1 ± 3.9; ZDF control (28 weeks) + ZDF Intervention control (21 weeks), 6.0 ± 0.8; Prevention, 63.6 ± 15.8; Intervention, 6.2 ± 0.9) and by morphological, immunohistochemical and electron microscopical examination of pancreata at the end of the study. Thus, islets from rosiglitazone Prevention rats were similar to ZL rats, whereas ZDF controls and Intervention rats exhibited islets depleted of insulin, with a disorganized architecture and an ultrastructure indicative of work hypertrophy. ZDF control rats and Intervention rats, though not rosiglitazone Prevention rats, also exhibited marked proteinuria, indicative of renal glomerular damage.

Conclusions  Our results demonstrate that in ZDF rats, rosiglitazone prevents the progression from insulin resistance to overt diabetes. These data provide a rationale for investigating whether treatment with rosiglitazone of patients with early signs of perturbed glucose metabolism (e.g. impaired fasting glucose (IGT)) may prevent the progression to type 2 diabetes and its associated complications.
Insulin release and suppression by tacrolimus, rapamycin and cyclosporin A are through regulation of the ATP‐sensitive potassium channel
Authors: Fuhrer D. K. , Kobayashi M. , Jiang H.
Published: March 2003

Summary

Aim  By focusing on the pancreatic β cell response to tacrolimus, cyclosporin A (CsA) and rapamycin we hoped to identify immunophilin, calcineurin and/or novel mechanism involvement and advance the understanding of immunosuppressant regulated insulin control.

Methods  A glucose responsive β cell model was established in which the glucose response was blocked by immunosuppressant treatment and this model was used to further characterise this effect. Quantification of insulin release to immunosuppressants and specific inhibitors was used to identify the mechanism involved.

Results  It was found that upon the addition of tacrolimus, rapamycin, or CsA, rapid and significant exocytosis of cellular insulin was seen. A dose response study of this effect revealed optimal concentration windows of 50– 80 nm for tacrolimus, 100–300 nm for rapamycin, and 7–12 mm for CsA in RIN‐5F cells. Optimal insulin release for HIT‐T15 cells was similar. Additional experiments demonstrate that immunosuppressant pretreatment blocked the subsequent immunosuppressant induced insulin release but not that of a thapsigargin control, suggesting that suppression and release are non‐toxic, specific and in the same pathway. Further experiments showed that this insulin release was a calcium dependent process, which was blocked by inhibitors of l‐type calcium channels. Continued studies showed that the specific ATP‐sensitive potassium channel agonist diazoxide (150 mm) also blocked immunosuppressant‐induced insulin release.

Conclusions  A model that fits this data is a novel calcineurin‐independent immunophilin mediated partial closing of the ATP‐sensitive potassium channel, which would lead to an initial insulin release but would reduce subsequent responses through this pathway.
Effect of acarbose on weight maintenance after dietary weight loss in obese subjects*
Authors: Hauner H. , Petzinna D. , Sommerauer B. , Toplak H.
Published: March 2003

SUMMARY

Aims   Acarbose is a well established antidiabetic drug and is known to exert a modest weight‐lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects.

Design   Randomised, double‐blind, placebo‐controlled trial of the effect of acarbose on weight change over a 6‐month follow‐up period.

Patients and Methods   One hundred and ten obese subjects with a BMI ≥ 32 and ≤ 38 kg/m2 were included in the study and underwent a 10–16‐week very‐low‐calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 ± 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per‐protocol population (n = 75).

Results   After an initial mean weight loss of 10.0 ± 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow‐up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable).

Conclusion   In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.
The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo‐controlled trial
Authors: Hanefeld M. , Sachse G.
Published: March 2003

Aim: To assess the long‐term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.

Methods: This was a multicentre, randomized, placebo‐controlled study with a 4‐week placebo plus diet lead‐in period and a 48‐week, double‐blind treatment period. Overweight or obese adults [body mass index (BMI) ≥ 28 kg/m2] with HbA1c of 6.5–11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low‐calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug‐naïve).

Results: After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (−5.4% vs. −3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of ≥ 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo‐treated patients in HbA1c (−0.9% vs. –0.4%; p < 0.001), fasting glucose (−1.6 vs.–0.7 mmol/l; p = 0.004) and post‐prandial glucose (−1.8 vs. –0.5 mmol/l; p = 0.003). In addition, orlistat‐treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat.

Conclusions: Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.
Rosiglitazone (PPARγ‐agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes–atherosclerosis mouse model
Authors: Levi Z. , Shaish A. , Yacov N. , Levkovitz H. , Trestman S. , Gerber Y. , Cohen H. , Dvir A. , Rhachmani R. , Ravid M. , Harats D.
Published: March 2003

Background: The administration of peroxisome proliferator‐activated receptor γ (PPARγ) agonists to low‐density lipoprotein (LDL)‐receptor‐deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)‐deficient mice rendered diabetic by low‐dose streptozotocin (STZ).

Methods: Male, apoE‐deficient mice (n = 48) were randomly divided into four groups. To induce diabetes, two groups received low‐dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non‐diabetic groups.

Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non‐diabetic apoE‐deficient mice: 340 ± 54 vs. 201 ± 27 μmol2 (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol2 (p = 0.001) in non‐diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone‐treated mice, both diabetic and non‐diabetic, had higher lipid levels.

Conclusions: Rosiglitazone‐treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti‐atherogenic effect of rosiglitazone on the arterial wall.
The pedal muscle of the land snail Megalobulimus oblongus (Gastropoda, Pulmonata): an ultrastructure approach
Authors: Faccioni‐Heuser M. Cristina , Zancan Denise M. , Lopes Christiane Q. , Achaval Matilde
Published: March 2003

M. Cristina Faccioni‐Heuser, Denise M. Zancan, Christiane Q. Lopes and Matilde Achaval. 1999. The pedal muscle of the land snail Megalobulimus oblongus (Gastropoda, Pulmonata): an ultrastructure approach. — Acta Zoologica (Stockholm) 80: 325–337

The ultrastructure of the pedal muscle of the Megalobulimus oblongus is described. This muscle consists of transverse, longitudinal and oblique bundles ensheathed in collagenous tissue. Each muscle cell is also ensheathed by collagen. The smooth muscle cells contain thin and thick filaments; the thin filaments are attached to dense bodies. These cells contain a simple system of sarcoplasmic reticulum, subsarcolemmal caveolae and mitochondria with dense granules in the matrix, and glycogen. Three types of muscle cells were identified. Type A cells exhibited densely packed myofilaments, abundant glycogen rosettes, numerous mitochondria and sarcoplasmic reticulum profiles. Type B cells exhibited scanty glycogen and mitochondria, few cisternae of sarcoplasmic reticulum and large intermyofibrillar spaces. Type C cells exhibited intermediate characteristics between type A and type B cells. Neither nexus nor desmosomes were observed between the muscle cell membranes. The muscle contains well developed connective tissue and blood vessels. These structures and the distribution of muscle cells are probably involved in the muscular‐hydrostat system. The muscle is richly innervated, having neuromuscular junctions with clear and electron‐dense synaptic vesicles. The clear vesicles probably contain acetylcholine because the axons to which they are connected arise from acetylcholinesterase positive neurones of the pedal ganglion. The other vesicles may secrete monoamines such as serotonin and/or neuropeptides such as substance P.
The significance of feeding for reproduction in a male Metastriata tick, Haemaphysalis longicornis (Acari: Ixodidae)
Authors: Matsuo Tomohide , Mo°ri Takayuki
Published: March 2003

In Haemaphysalis longicornis, secretions of the male accessory genital glands were regenerated by re‐feeding for 3 or 4 days, although the secretions were almost completely released during the first copulation. It was also shown that spermatogenesis continued during re‐feeding, since prospermia (elongated spermatids) were deposited in the seminal vesicle. A potent male seeks a receptive female on the host for copulation. The movement of males to different attachment sites occurred between the third and fourth day of re‐feeding, and completely re‐fed males (for 4 days) were able to copulate successfully. Spermatogenic cells, ranging from spermatogonia at the anterior end to prospermia at the posterior end, were found in fed males. Degeneration of spermatocytes at the great growth phase and developing spermatids prior to final development of prospermia were seen in virgin males without re‐feeding after the first meal. Fully elongated spermatids (prospermia) appeared morphologically normal up to 10 days after the first feeding. Degeneration of spermatocytes and developing spermatids occurred from the second day and was almost complete by the fourth day. The degenerating cells shrank, became electron‐dense, and finally died. A reduction in secretions of the four lobes of the accessory glands occurred during the 10 days after feeding.
The mesopneumonia and the post‐hepatic septum of the Teiioidea (Reptilia: Squamata)
Authors: Klein Wilfried , Böhme Wolfgang , Perry Steven F.
Published: March 2003

Klein, W., Böhme, W. and Perry, S. F. 2000. The mesopneumonia and the post‐hepatic septum of the Teiioidea (Reptilia: Squamata). —Acta Zoologica(Stockholm)81: 109–119

This study investigates the structure of the pleuroperitoneal cavity of Teiioidea. Seven of nine genera of Teiidae and eight of 35 genera of Gymnophthalmidae were dissected and the results are presented in a highly schematic two‐dimensional representation. The main anatomical differences between the two families are (1) the presence of a hepatic ligament which fuses with the pericardiaco‐peritoneal septum in the Gymnophthalmidae but not in the Teiidae; (2) the presence of a ventral mesopneumonium on the right side in the Gymnophthalmidae, while this structure is secondarily lacking in the Teiidae; (3) that the post‐hepatic septum of Teiidae consists of a bipartite hepatic ligament and the ventral mesentery, while in gymnophthalmids the hepatic ligament remains undivided.NeusticurusandEchinosauracompletely lack a post‐hepatic septum. The results are consistent with the hypothesis that the Gymnophthalmidae are primitive within the Teiioidea and that the Tupinambinae are the most highly derived teiids. We propose that the post‐hepatic septum may restrict passive visceral movement during breathing, thereby increasing the efficiency of respiratory effort; a modification that could benefit the fitness of active, predatory teiids.
Locomotory design of ‘cyclostome’ fishes: Spatial arrangement and architecture of myosepta and lamellae
Authors: Vogel Felix , Gemballa Sven
Published: March 2003

Vogel, F. and Gemballa, S. 2000. Locomotory design of ‘cyclostome’ fishes: Spatial arrangement and architecture of myosepta and lamellae. —Acta Zoologica (Stockholm) 81: 267–283

In recent years, it has been established that the main features of the locomotory apparatus of gnathostome fishes (myoseptal and muscular system) have remained relatively unchanged throughout evolution. The petromyzontiforms (lampreys) and myxiniforms (hagfishes) display a similar way of undulatory locomotion as gnathostomes. We investigated whether the anatomical features of the myoseptal system that facilitate undulatory locomotion in gnathostomes are also present in lampreys and hagfishes. We present a description of the myoseptal system, including for the first time the spatial arrangement and fibre architecture in ‘cyclostomes’, using a clearing technique, microdissections, polarized light microscopy, and SEM. We revealed that the myoseptal system of the Myxiniformes, Petromyzontiformes and Gnathostomata are each constructed in different ways. Petromyzontiform myosepta lack the conical structures but bear tendon‐like structures in the flanking parts. Their central parts lack tendon‐like structures but possess a system of crossing collagen fibres. Myxiniform myosepta bear comparable conical structures as gnathostomes but a highly asymmetric spatial arrangement. The fibre architecture of myosepta is not comparable to any of the two remaining taxa. The collagen fibre architectures of the multiple horizontal sheets of lamellae in ‘cyclostomes’ and the gnathostome horizontal septum are comparable. Our results 1) support the monophyly of Myopterygii (Petromyzontiformes + gnathostomes and a sistergroup relationshop of Myopterygii and Myxiniformes; 2) demonstrate that considerable changes must have taken place in the locomotory apparatus early in vertebrate evolution.
Locomotory and feeding effectors of the tornaria larva of Balanoglossus biminiensis
Authors: Lacalli T. C. , Gilmour T. H. J.
Published: March 2003

Lacalli, T. C. and Gilmour, T. H. J. 2001. Locomotory and feeding effectors of the tornaria larva of Balanoglossus biminiensis. —Acta Zoologica (Stockholm) 82: 117–126

The tornaria ciliary bands and oesophagus were examined ultrastructurally to identify the neural components that control larval behaviour. The circumoral ciliary band is known to be innervated in part by fibres from the apical plate and adoral nerve centres. Within the band itself, however, the only neurones we could find were multipolar cells, an unusual cell type with apical processes that traverse the surface of the band. Similar cells occur in the circumoral bands of echinoderm larvae. The tornaria telotroch has a much larger nerve, but no neurones were found either in the band or nearby, so the source of the fibres in the telotroch nerve remains unknown. In addition to having different innervation, the two bands also respond differently to cholinergic agonists, which elicit telotroch arrests but have no visible effect on the circumoral band. The oesophagus has a well‐developed musculature and an extensive nerve plexus. During feeding, the oesophagus repeatedly contracts, forcing excess water out along two lateral channels prior to swallowing. These channels are also sites of gill slit formation, so there is evidently a continuity between the water bypass mechanism of the larva and that of the postmetamorphic juvenile.
Functional morphology of the male genitalia and copulation in lower Hymenoptera, with special emphasis on the Tenthredinoidea s. str. (Insecta, Hymenoptera, ‘Symphyta’)
Authors: Schulmeister Susanne
Published: March 2003

A general description of the male reproductive organs of lower Hymenoptera is given. The terminology of the male genitalia is revised. The male external genitalia of Tenthredo campestris are treated in detail as a specific example of the morphology. The interaction of the male and female parts during copulation is described for Aglaostigma lichtwardti. The possible function of sclerites and muscles of the male copulatory organ of Tenthredinoidea s. str. is discussed. Additional observations on morphology and function made in non‐tenthredinoid lower Hymenoptera are included. The assumption that the gonomaculae act as suction cups is confirmed for the first time. The evolution of obligate and facultative strophandry is discussed. The stem species of all Hymenoptera was probably orthandrous and facultatively strophandrous.
Minireview: On the homology of the protocoel in Cephalochordata and ‘lower’ Deuterostomia
Authors: Stach Thomas
Published: March 2003

Hypotheses regarding the homology of the protocoel in planktonic deuterostome larvae and mesodermal structures in ontogenetic stages of cephalochordates are evaluated. The prevalent ‘classical’ hypothesis describes the protocoel as being homologous with the diverticula of Hatschek, which, on the left side, develop into the preoral pit, subsequently into Hatschek’s pit and groove (in part). This hypothesis is based mainly on the position of Hatschek’s diverticula anterior to the rest of the mesoderm during their enterocoelic origin. It is shown here that during development the mesodermal segment that develops into Hatschek’s nephridium is the most anterior one prior to formation of Hatschek’s diverticula, and this segment assumes an anteriormost position after differentiation of Hatschek’s diverticula. Additional similarities between this segment and protocoels are: (i) presence of endomesodermal cells with podocytic extensions, (ii) excretory function, (iii) relatively early ontogenetic origin, (iv) probable lack of association with nervous structures, (v) probable ectodermal origin of a portion of the canal, and (vi) position relative to the mouth opening. Therefore, homology between the protocoel and the segment that becomes Hatschek’s nephridium is proposed. It is concluded that a glandular structure homologous to the diverticula of Hatschek and anterior to the protocoel/Hatschek’s nephridium is a synapomorphy of notochordates or chordates.
Ultrastructure of the mature spermatozoon of the musky rat‐kangaroo, Hypsiprymnodon moschatus (Potoroidae: Marsupialia)
Authors: Lloyd S. , Carrick F. , Hall L.
Published: March 2003

It is currently accepted that Hypsiprymnodon moschatus is a basal macropod, retaining several primitive features from the ancestral phalangeroid that gave rise both to modern possums and macropods. Sperm ultrastructure is frequently found to provide informative characters for phylogenetic analysis as these features are not strongly selected for and are thus unlikely to be confounded by effects such as convergence. Caudal epididymal biopsies were taken from two male H. moschatus and prepared for transmission and scanning electron microscopy in order to study mature spermatozoan ultrastructure. Within the diprotodont group, several features were found to be unique to H. moschatus. These were an unusual acrosome covering nearly 100% of the dorsal nuclear surface, a midpiece fibre network which is loose, indistinct and extends to the anterior‐most aspect of the midpiece, a nucleus that is very streamlined, while the principal piece is comparatively short, and a mitochondrial helix and annulus which are similar to those of dasyurids. Also reported is the presence of a fibrous network in the connecting piece, not previously reported for any marsupial.