Urolithiasis in Jordanian children. A report of 52 cases

Fifty-two children with urinary calculi seen between 1975 and 1986 were reviewed. Males dominated the series. The age distribution ranged from 10 months to 14 years (mean 7.2 years); 71% presented after school age. Most patients had upper tract stones. The main presenting symptoms were abdominal pain, infection and haematuria. The causative factors or co-factors were infection, malformations and urodynamic abnormalities. Metabolic disorders were rare. Calcium oxalate and uric acid stones were found most often. Surgical management was required in 88% of patients and only 3.8% had a recurrence. Presenting symptoms are variable and so a high index of suspicion is required for diagnosis.     

Antibody Responses to Group A Streptococcal Infections in the Hamster

The immune response after streptococcal infections of the skin and of the joints was studied in an experimental animal model. Hamsters were challenged intradermally or intra-articularly with different streptococcal serotypes, and antibodies for streptolysin O (ASO), deoxyribonuclease B (anti-deoxyribonuclease B), and group A carbohydrate (anti-group A CHO) were determined. After a single injection at either site, 7 of 48 animals (14%) developed group A-CHO antibodies; however, none of the animals developed detectable levels of ASO or anti-deoxyribonuclease B. After repeated infections of the skin or joint, anti-deoxyribonuclease B antibodies were detectable in 13% (4 of 30) and 30% (5 of 17) of the animals, respectively. Elevations of ASO occurred after repeated joint infections in 4 of 16 animals (25%), whereas none of 30 hamsters repeatedly infected intradermally developed antibodies against streptolysin O. For all three antibodies tested, elevated levels were more frequently noted after repeated joint infections than after repeated skin infections with the same streptococcal serotype. These data, similar to ones previously noted in human impetigo, indicate that ASO responses are feeble after streptococcal skin infections and that the site of infection per se, rather than the infecting strain, appears to be responsible for this poor response.     

Type II antithrombin deficiency caused by a large in‐frame insertion: structural,functional and pathological relevance

Summary. Background: The metastable native conformation of serpins is required for their protease inhibition mechanism, but also renders them vulnerable to missense mutations that promote protein misfolding with pathological consequences. Objective: To characterize the first antithrombin deficiency caused by a large in‐frame insertion. Patients/Methods: Functional, biochemical and molecular analysis of the proband and relatives was performed. Recombinant antithrombin was expressed in HEK‐EBNA cells. Plasma and recombinant antithrombins were purified and sequenced by Edman degradation. The stability was evaluated by calorimetry. Reactive centre loop (RCL) exposure was determined by thrombin cleavage. Mutant antithrombin was crystallized as a dimer with latent plasma antithrombin. Results: The patient, with a spontaneous pulmonary embolism, belongs to a family with significant thrombotic history. We identified a complex heterozygous in‐frame insertion of 24 bp in SERPINC1, affecting strand 3 of β‐sheet A, a region highly conserved in serpins. Surprisingly, the insertion resulted in a type II antithrombin deficiency with heparin binding defect. The mutant antithrombin, with a molecular weight of 59 kDa, had a proteolytic cleavage at W49 but maintained the N‐terminal disulphide bonds, and was conformationally sensitive. The variant was non‐inhibitory. Analysis of the crystal structure of the hyperstable recombinant protein showed that the inserted sequence annealed into β‐sheet A as the fourth strand, and maintained a native RCL. Conclusions: This is the first case of a large in frame‐insertion that allows correct folding, glycosylation, and secretion of a serpin, resulting in a conformationally sensitive non‐inhibitory variant, which acquires a hyperstable conformation with a native RCL.     

Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage. A double-blind endoscopic study in human subjects

This randomized, double-blind, placebo-controlled study compared the cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, and cimetidine on ethanol-induced gastric mucosal damage. Forty-five healthy male subjects were accepted, following endoscopy to exclude those with upper gastrointestinal disease. Injury to the gastric mucosa was induced by spraying it with 80% ethanol solution. Misoprostol (200 micrograms) intragastrically or cimetidine (300 mg) orally or placebo was administrated before the ethanol challenge. The gastric mucosa was graded using a seven-point endoscopic scale by two endoscopists 15 and 30 min after ethanol instillation. Thirty minutes following the instillation of ethanol, the gastric mucosa of placebo-treated subjects showed marked damage, with an endoscopic score (mean +/- standard deviation) of 5.5 +/- 0.9. Cimetidine partially prevented gastric mucosal damage, with an endoscopic score of 4.5 +/- 1.7 as compared to placebo (p = 0.04). Misoprostol significantly prevented gastric mucosal injury with a mean endoscopic score of 1 +/- 1.7 when compared to placebo (p = 0.0001) and to cimetidine (p = 0.0002). This cytoprotective action of misoprostol may prove to be clinically very important and warrants further investigation.     

Acute surgical unit safely reduces unnecessary after-hours cholecystectomy

Introduction

The acute surgical model has been trialled in several institutions with mixed results. The aim of this study was to determine whether the acute surgical model provides better outcomes for patients with acute biliary presentation, compared with the traditional emergency surgery model of care.

Methods

A retrospective review was carried out of patients who were admitted for management of acute biliary presentation, before and after the establishment of an acute surgical unit (ASU). Outcomes measured were time to operation, operating time, after-hours operation (6pm – 8am), length of stay and surgical complications.

Results

A total of 342 patients presented with acute biliary symptoms and were managed operatively. The median time to operation was significantly reduced in the ASU group (32.4 vs 25.4 hours, p=0.047), as were the proportion of operations performed after hours (19.5% vs 2.5%, p<0.001) and the median length of stay (4 vs 3 days, p<0.001). The median operating time, rate of conversion to open cholecystectomy and wound infection rates remained similar.

Conclusions

Implementation of an ASU can lead to objective differences in outcomes for patients who present with acute cholecystitis. In our study, the ASU significantly reduced time to operation, the number of operations performed after hours and length of stay.     

Objective measurement of physiological signal-to-noise gain in the brainstem response to a synthetic vowel

ObjectiveThis work investigates auditory speech processing in normal listeners through measurement of brainstem responses to the synthetic vowel /a/.MethodsThe vowel is presented in quiet and in continuous white noise with different signal-to-noise ratios (SNR) of +5, 0, ?5, and ?10 dB.ResultsIn the presence of noise, transient response waves V and A are delayed when compared to those evoked in quiet, whereas the amplitude of wave V and the steepness of the slope between waves V and A are strongly reduced. The spectral component of the steady-state evoked response corresponding to the fundamental frequency (F0) of the vowel shows significantly greater amplitude and local SNR in the less severe noise conditions compared to the quiet condition. Such increases of the amplitude and SNR were not observed for the spectral component corresponding to the first formant of the vowel (F1).ConclusionsResults suggest that, at F0, both local noise suppression and signal enhancement contribute to the SNR gain. There is suppression of local noise near F1, but no signal enhancement.SignificanceThe physiological SNR gain was estimated to be approximately +12 dB at both F0 and F1, as stimulus SNR was reduced from +5 to ?10 dB.     

Lipid rafts keep NADPH oxidase in the inactive state in human renal proximal tubule cells

Recent studies have indicated the importance of cholesterol-rich membrane lipid rafts (LRs) in oxidative stress-induced signal transduction. Reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases, the major sources of reactive oxygen species, are implicated in cardiovascular diseases, including hypertension. We tested the hypothesis that NADPH oxidase subunits and activity are regulated by LRs in human renal proximal tubule cells. We report that a high proportion of p22(phox) and the small GTPase Rac1 are expressed in LRs in human renal proximal tubule cells. The D(1)-like receptor agonist, fenoldopam (1 micromol/L per 20 minutes) dispersed Nox subunits within LRs and non-LRs and decreased oxidase activity (30.7+/-3.3%). In contrast, cholesterol depletion (2% methyl-beta-cyclodextrin [beta CD]) translocated NADPH oxidase subunits out of LRs and increased oxidase activity (154.0+/-10.5% versus control, 103.1+/-3.4%), which was reversed by cholesterol repletion (118.9+/-9.9%). Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%). Furthermore, beta CD-induced reactive oxygen species production was reversed by knocking down either Nox2 (81.0+/-5.1% versus beta CD: 162.0+/-2.0%) or Nox4 (108.0+/-10.8% versus beta CD: 152.0+/-9.8%). We have demonstrated for the first time that disruption of LRs results in NADPH oxidase activation that is abolished by antioxidants and silencing of Nox2 or Nox4. Therefore, in human renal proximal tubule cells, LRs maintain NADPH oxidase in an inactive state.     

Injury to the femoral vessels--the Lebanese War experience

Over a 10-year-period extending from January 1976 to September 1986, 800 peripheral vascular injuries were surgically treated at the American University of Beirut Medical Centre. Of these, 150 were operated on because of injury to the femoral vessels. Bullets were the commonest wounding agents (60% of cases). Thirty-seven patients had a femoral artery injury, 27 a femoral vein injury and 86 combined femoral artery and vein damage. Twenty-three per cent of the patients had an associated fracture of the femur. Patients with fractures had an 11% amputation rate compared with 1% for those without fractures. Our data reveals the importance of venous reconstruction in the presence of an arterial injury instead of its ligation (P less than 0.05), particularly when there is an associated fracture of the femur. Thirty-seven per cent of patients were in shock on admission (systolic BP 90 mmHg). The amputation rate in these patients was 6.8% in contrast to 1% in the haemodynamically stable group (P less than 0.05). The overall amputation rate was 3.3%. Complications occurred in 36.6% of patients and the mortality was 4.0%.     

Cancer prevention education in United States medical schools: How far have we come?

Nearly 20 years ago, the American Association of Cancer Education conducted a pioneering survey on the status of cancer prevention and detection education at US medical schools. Eight recommendations to improve teaching followed. In the ensuing 20 years, modest progress has been made in realizing these objectives. Herein, we review progress to date and call for a national forum of anti-cancer organization to forge a new series of competencies for all US medical students.