Senior's syndrome (hereditary renal retinal dysplasia) associated with cataracts.

Senior's syndrome includes nephronophthisis with retinitis pigmentosa. In our patient, there was a combination of bilateral retinitis pigmentosa, cataracts, nephronophthisis, osteomalacia, growth and mental retardation, arterial hypertension, and aortic insufficiency. This case was unusual because all the features of Senior's syndrome existed along with bilateral cataracts from childhood.     

Correlation of radiographic and endoscopic evaluation of gastrojejunal anastomosis after Roux-en-Y gastric bypass.

BACKGROUND: Anastomotic stenosis presents as one of the most common late complications in the postoperative period after bariatric surgery. It is often diagnosed by upper gastrointestinal series (UGIS) and/or upper endoscopy (UE). The aim of this study was to determine whether a correlation exists between the Gastrografin UGIS and UE findings in the determination of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass (RYGB). METHODS: Between July 2001 and October 2003, all medical records of patients who underwent RYGB at our institution were retrospectively reviewed. The medical records of patients who underwent UE because of symptoms suggestive of gastric outlet obstruction and those of patients who were initially evaluated by Gastrografin UGIS before UE were evaluated further. RESULTS: Of 535 morbidly obese patients who underwent RYGB, 52 (9.7%) had UE and were included in this study. The mean number of UEs performed per patient was 2.67. Of these 52 patients, 30 underwent Gastrografin UGIS before UE. The mean diameter of the anastomosis on the first UE was 5.97 mm and on Gastrografin UGIS was 6.83 mm. A good correlation was found between the Gastrografin UGIS and UE findings using Pearson's correlation coefficient (0.44, P = .02) and single linear regression analysis using the endoscopic diameter as the outcome and radiographic findings as the predictor (beta = 0.27, P = .025, 95% confidence interval 0.30-0.49). CONCLUSION: In our study, the Gastrografin UGIS findings correlated positively with the endoscopic gastrojejunal anastomosis findings in patients with anastomotic stricture who had undergone RYGB.     

Verhandlungen der Berliner dermatologischen Gesellschaft

Ohne Zusammenfassung     

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. METHODS: Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.     

Insulin inhibition of endothelial prostacyclin production

Graft thrombosis is a common cause of early graft failure in pancreatic transplantation, even in the absence of rejection. Altered endothelial cell (EC) production of thromboactive substances may play a primary role in this and other settings of thrombosis where intraluminal insulin concentrations are high. We therefore investigated the effect of insulin on EC production of prostacyclin (PGI2), a potent endogenous antagonist of platelet aggregation and vasodilator. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated for 15 min in Hanks'/Hepes buffer containing 0, 50, 250, or 500 microU/ml of human insulin or 0, 500, 1000, or 2000 microU/ml of porcine insulin. PGI2 production was assessed by exposing the monolayers to either 20 microM arachidonic acid (stimulated) or arachidonic acid vehicle (basal) for an additional 15 min. Test buffers were then assayed by RIA for 6-keto-PGF1 alpha, the stable metabolite of PGI2. The results of these experiments indicate that human insulin inhibits both basal and arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. Inhibition of stimulated production was significant at concentrations of 250-500 microU/ml. Porcine insulin also inhibited arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. However, HUVEC were less sensitive to porcine insulin than to human insulin and a concentration of 2000 microU/ml was required for significant inhibition. We therefore conclude that insulin, in locally high concentrations, inhibits endothelial PGI2 production in vitro. The ability of insulin to alter the production of thromboresistant substances from endothelium may facilitate thrombosis in circumstances where counterregulatory mechanisms are disturbed by injury or transplantation.     

Major fragment of soluble peptidoglycan released from growing Bordetella pertussis is tracheal cytotoxin.

Bordetella pertussis is known to release a factor which promotes the loss of ciliated respiratory epithelium and copurifies with a soluble peptidoglycan (PG) fragment termed tracheal cytotoxin (TCT). The objective of this study was to determine whether pertussis organisms turn over and release PG derivatives in addition to TCT. B. pertussis Tohama (phase III) was grown in liquid Stainer-Scholte medium containing [3H]diaminopimelic acid (DAP) to label PG specifically, washed to remove free label, and suspended in fresh medium without [3H]DAP. Molecular sieve chromatography of supernatants obtained from such cultures revealed a single included peak of 3H, the elution volume of which corresponded roughly to a disaccharide peptide monomer standard (ca. 10(3) daltons). This material (i) contained [3H]DAP in acid-hydrolyzable linkage, (ii) comigrated with 1,6-anhydro-N-acetylmuramic acid-containing disaccharide peptides on paper chromatography, (iii) was resistant to degradation by mild alkali, and (iv) was indistinguishable from authentic TCT by high-voltage paper electrophoresis and two reversed-phase high-performance liquid chromatography systems. Together, the data suggest that B. pertussis releases a markedly homogeneous set of PG fragments, consisting principally of TCT, and that TCT is possibly a nonreducing, anhydromuramic acid-containing fragment or a cyclic PG derivative.     

Pentamidine blocks the pathophysiologic effects of endotoxemia through inhibition of cytokine release.

Pentamidine isethionate, an antiprotozoal agent with therapeutic value against Pneumocystis carinii pneumonia, has been used for over 30 years without a precise understanding of its mechanism of pharmacologic action. We have previously reported that pentamidine has the capacity to inhibit the release of cytokines from macrophages through a post-translational processing event. The present studies were undertaken to assess the ability of pentamidine to modulate the detrimental effects of murine endotoxemia, a disease with a pathophysiology clearly linked to host-produced cytokines. Under conditions where normal B6C3F1 mice succumbed to the lethal effects of endotoxin, mice pretreated with pentamidine were significantly protected from both mortality and loss of thermoregulatory control. The EC50 for protection from mortality by pentamidine was approximately 11.4 mg/kg. These observations correlated with decreased serum levels of tumor necrosis factor (TNF) and interleukin 6. Inhibition of cytokines was not manifested as part of a generalized inhibition of protein synthesis as demonstrated by the lack of significant modulation of serum albumin in pentamidine-treated animals. In addition to decreased serum concentrations of cytokines, lungs isolated from mice treated with both pentamidine and endotoxin exhibited a decreased release of TNF compared to lungs isolated from mice treated with vehicle and endotoxin. The lower levels of TNF released from lung tissue in pentamidine-treated mice correlated with a lesser degree of alveolar deterioration than was observed in vehicle-treated mice. These data indicate that following endotoxin administration, pentamidine has a protective and antiinflammatory role both systemically and in the lung and suggest that inhibition of inflammatory cytokines may be one mechanism operable in the therapeutic activity of the drug against P carinii pneumonia.     

Promoting clinically effective practice: general practitioners' awareness of sources of research evidence

BACKGROUND: Practitioners are being encouraged to base their clinical practice on research evidence. In order to do this, they must be aware of and use the sources of evidence. METHODS: A questionnaire survey was undertaken to establish GPs' awareness of research evidence in their clinical practice and, in fundholding practices, its influence on purchasing plans. Questionnaires were sent to 360 lead fundholders in North Thames Region and 440 of a random sample of the remaining general practitioners in the region for comparison. RESULTS: Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the random sample. There was limited use of the electronic sources of clinical effectiveness. There was greater reported awareness of published sources of research evidence and fundholding GPs were significantly more likely to have referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to make more use of published clinical effectiveness sources than the electronic databases. Consequently, they need educational and technical support if they are to make full use of the available sources of research evidence available in other media.