Experimental intrauterine growth retardation alters renal development

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation (IUGR), resulting in small-for-gestational-age, asymmetric newborns. IUGR neonates experience higher morbidity and mortality rates, as well as a possible contribution towards late sequelae, such as hypertension, and cardiovascular disease in adulthood. To simulate vascular placental insufficiency, an experimental rabbit IUGR model was used. Intrauterine growth retardation was achieved by ligation of 25–30% uteroplacental vessels of half of the fetuses during the last third of gestation. Ischemic fetuses were significantly small, asymmetric, and had a disproportionately small body with a relatively large head. The kidneys from all groups were analyzed for relative estimated glomeruli number (REGN) using an unbiased blind design. The glomeruli number was significantly reduced in the asymmetric IUGR rabbit fetuses, probably due to decreased renal vascular supply. Our results support the concept that the reduced number of glomeruli may contribute to impaired renal function, thus predisposing to neonatal renal dysfunction and late sequelae, such as adult hypertension. This study emphasizes the clinical importance of early IUGR diagnosis and prevention. Received: 15 February 2000 / Revised: 26 June 2000 / Accepted: 29 June 2000     

Biomimetic models for monooxygenases

The microsomal mixed function oxidase system contains the cytochrome P-450 oxidative drug metabolizing family of enzymes. The catalytic cycle of cytochrome P-450 is believed to involve the formation of an active iron-oxygen species which is responsible for oxygen transfer to the substrate. This assumption is supported by the fact that a number of peroxidative agents can replace NADPH, the reductase, and oxygen as co-reactants in most oxidative reactions of microsomal cytochrome P-450. We have found that a mixture of either ferrous or ferric ions with hydrogen peroxide (Fenton and Ruff reagents) can serve as biomimetic models for cytochrome P-450 in hydroxylation, exposidation, sulfoxidation, and N-demethylation of various drugs. The existance of an iron-oxo active species in both Fenton and Ruff type reactions has been postulated and provides reaction cycles similar to those of cytochrome p-450. Other model systems for the hepatic hydroxylation and epoxidation using transition metal complexes with porphyrin are also discussed. The present paper reviews the various biomimetic models of the heme cytochrome P-450 and emphasizes their simulation of hepatic drug metabolism and their potential medical and industrial applications.     

Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli

As a large number of cancers are caused by nonsense mutations in key genes, read-through of these mutations to restore full-length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations. Our goal was to test the feasibility and effectiveness of APC nonsense mutation read-through as a potential chemo-preventive therapy in Familial Adenomatous Polyposis (FAP), an inherited CRC syndrome patients. Ten FAP patients harboring APC nonsense mutations were treated with the read-through inducing antibiotic erythromycin for 4 months. Endoscopic assessment of the adenomas was performed at baseline, after 4 and after 12 months. Adenoma burden was documented in terms of adenoma number, maximal polyp size and cumulative polyp size per procedure. Tissue samples were collected and subjected to molecular and genetic analyses. Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number. Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor-suppressing activity. Together, our findings show that induced read-through of APC nonsense mutations leads to promising clinical results and should be further investigated to establish its therapeutic potential in FAP and sporadic CRCs harboring nonsense APC mutations.     

CO(2) Laser Fascia to Dura Soldering for Pig Dural Defect Reconstruction.

Background and objectives: The purposes of this study were to demonstrate that laser soldering is safe and effective for tissue bonding in dural reconstruction and to compare this new reconstruction technique to an established one. Study design: A temperature-controlled fiberoptic CO(2) laser system or fibrin glue were used for in vitro dural defect reconstruction in two groups of pigs. The CO(2) laser technique was also used for dural reconstruction in live pigs. Results: The burst pressure of the reconstructed dura by the laser system was significantly higher than that of fibrin glue (mean pressure 258.5 +/- 117.3 cm H(2)O and 76.8 +/- 47.2 cm H(2)O, respectively). There were no postoperative complications and no signs of thermal damage to the dura, fascia, or underlying tissue on histological analysis following the in vivo CO(2) laser experiments. Conclusions: Temperature-controlled laser soldering is an effective technique for dural repair. It creates a strong tissue bonding with no thermal damage to the tissue. The burst pressure of the reconstructed dura done with laser soldering is significantly higher than that of fibrin glue.     

Functional outcome of collagenase injections compared with fasciectomy in treatment of Dupuytren’s contracture

Background

This study was designed to provide comparative information on the safety and efficacy of injection with collagenase clostridium histolyticum (CCH) and fasciectomy for patients with Dupuytren’s contracture (DC).

Methods

A single-center, retrospective, observational, longitudinal chart review was conducted of 25 patients treated with CCH injections and 21 patients undergoing fasciectomy. Patients were assessed at 1 week, monthly for 3 months and then yearly for a minimum of 2 years after treatment for changes in contracture and range of motion, time to return to work/normal activities, patient satisfaction, and Disabilities of Arm, Shoulder and Hand (DASH) score.

Results

Post-procedure follow-up averaged 32 months for the injection group compared with 39 months for fasciectomy group. For the CCH group, the mean postinjection contracture was 3.6° for the metacarpophalangeal and 17.5° for the proximal interphalangeal joints compared with 3.7° and 8.1° in the fasciectomy group, respectively. Patients treated with injections returned to normal activities after a mean of 1.9 days compared with 37.4 days for fasciectomy patients (p < 0.0001). DASH scores for 13 CCH and 15 fasciectomy patients were obtained. The mean DASH score was significantly lower in the injection group in the first 3 months (p < 0.01). At the 2-year follow-up visit, patients were satisfied with their outcomes following either treatment (92 % and 96 % of CCH and fasciectomy patients, respectively).

Conclusion

CCH injections are safe and effective and may be a viable alternative to fasciectomy for treating DC. It also allows earlier return to work and daily activities.     

Diagnostic yield of colonoscopy for constipation as the sole indication

Aim There is controversy over whether constipation as the only symptom should be an indication for routine diagnostic colonoscopy. The study was carried out to assess the prevalence of abnormal pathology on colonoscopy and to assess the risk factors for colonic neoplasia in patients with constipation but without ‘high risk symptoms’. Method A cross‐sectional, single‐centre study was conducted on individuals who underwent colonoscopy for constipation as the sole indication between 2005 and 2008. Standardized endoscopic and pathology reports were reviewed. Univariable and multivariable analyses were performed. Results A total of 786 patients (595 women, 75.7%; mean age, 57.4 ± 13.5 years) underwent diagnostic colonoscopy for constipation. Forty‐three (5.5%) had polyps, of whom 19 (2.4%) had hyperplastic polyps and 19 (2.4%) adenomas. No cancers were found. In patients with adenoma, the detection rate was 2.9% for patients below age 40 years and 1.7% for patients below age 50 years. Older age was associated with a polyp in both univariate and multivariate analysis. Gender, ethnicity and smoking were not associated with polyp or adenoma. Conclusion Colonoscopy for patients with constipation as the sole indication had a lower yield of neoplastic lesions than that for patients undergoing routine screening colonoscopy. Colonoscopy in constipation may only be warranted in patients who are over 50 years of age.     

Familial cardiomyopathy With special consideration of electrocardiographic and vectorcardiographic findings

Fourteen cases of familial cardiomyopathy occurring in three Jewish families and affecting both sexes in two generations, have been described. The earliest manifestation of the disease was an abnormal electrocardiogram, with subjective difficulties appearing much later. The importance of the cardiogram as a means of early diagnosis of the disease, especially in asymptomatic members of the family, has been confirmed. The dynamic nature of the cardiographic changes has been stressed and a tentative correlation between the changes in the electrical activity of the heart and the anatomical pathogenesis has been proposed. In the 2 fatal cases, autopsy revealed a similar picture of cardiac enlargement with thickening of the walls of the ventricles and interventricular septum and severe fibrosis histologically.

The mutant gene responsible for the disease is apparently transmitted as an autosomal dominant trait.