Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts

Certain end-products of lipid peroxidation bind to DNA forminga fluorescent chromophore. Incubation of both Salmonella typhimuriumTA104 and a rat lung fibroblast cell line, RFL-6, with varioustypes of mineral fibre resulted in a time- and dose-dependentincrease in DNA fluorescence. The increase in DNA fluorescencewas shown to be directly related to the amount of iron thatcould be mobilized from the fibre surface using in vitro studiesin the absence of cells or bacteria. Crocidolite and man-madevitreous fibre-21 (MMVF-21) mobilized significant quantitiesof iron and were significantly more active than chrysotile andrefractory ceramic fibre-1 (RCF-1). Fibre-induced malon-dialdehyde-DNAadduct formation, the fluorescent product, was increased byincubating cells with buthionine sulfoximine and amelioratedby co-treatment with N-acetylcysteine, indicating a protectiverole for glutathione. Similarly, vitamin E was also shown toinhibit DNA adduct formation. These results suggest that mineralfibre-induced lipid peroxidation produces genotoxic productswhich can diffuse into the nucleus and interact with cellularDNA. In conclusion, fibre-induced lipid peroxidation may bea possible mechanism in the genotoxic action of fibrous materials.     

Bleeding peptic ulcer: An evolving role for surgical intervention

Abstract Early surgical intervention was previously advocated in patients > 60 years with bleeding peptic ulcer presenting with haemodynamic instability or ongoing transfusion requirements. It is, however, well recognized that emergency surgical intervention with its inherent risks must be reserved for highly selected patients in whom endoscopy initially fails to control exsanquinating haemorrhage or in whom life-threatening bleeding recurs. Therapeutic endoscopy for bleeding ulcer has led to a remarkable decline in rebleeding rates, the need for emergency surgery and mortality. Octogenarians are at risk, particularly when ulcer size exceeds 2 cm. Poor surgical candidates make up two-thirds of patients with major ulcer bleeding and operation is to be avoided if at all possible. Medical therapy with proton pump inhibitor and subsequent eradication of Helicobacter pylori following endoscopic treatment has been shown to be beneficial to outcomes. Should surgery be deemed necessary, it is likely that laparoscopic techniques to control bleeding, with or without the addition of an acid-reducing procedure, will find a role in haemodynamically stable patients undergoing operation on an early elective basis.     

Surgical procedures for urethral diverticula in women in the United States, 1979–1997

The objective of this study was to describe national rates of surgery for urethral diverticula in women. Data from the National Hospital Discharge Survey (NHDS), a federal database that samples inpatient hospitals in the United States, were analyzed from 1979 to 1997 for diagnosis and procedure codes using the ICD-9-CM classification system. The difference between the median age-adjusted rates from 1979 to 1988 and 1989 to 1997 were evaluated using the Mann-Whitney U test since the yearly rates fluctuated in a nonlinear fashion. Data from the National Statistics for Ambulatory Surgery (NSAS) database were analyzed from 1994 to 1996 in a similar fashion. The average age of women undergoing surgery for urethral diverticula increased from 41.6±15.1 years from 1979 to 1988 to 49.4±14.8 years from 1989 to 1997 (p=0.02). The average length of hospital stay decreased from 8.4±5.0 days in 1979 to 3.2±1.7 days in 1997 (p=0.007). Approximately 27,000 inpatient procedures were performed for the repair of urethral diverticula in the United States over a 19-year period, ranging from an estimated 500 to 3400 cases per year. The median age-adjusted rate of procedures decreased from 14.2 per 1 million women from 1979 to 1988 to 6.4 per 1 million women from 1989 to 1997 (p=0.009). Data from the NSAS indicated that an average of 6.7 surgeries per 1 million women per year were performed in the outpatient setting from 1994 to 1996. Age-adjusted rates of inpatient surgery for urethral diverticula were threefold higher for black compared to white women. Inpatient surgical repair of urethral diverticula is three times as high in black as compared to white women. These procedures are infrequent and rates appear to have decreased over time.This research has been presented in abstract form in March 2003 at the Annual Meeting of the Society of Gynecologic Surgeons     

A method for the detection of IgE binding sequences of allergens based on a modification of epitope mapping

An ELISA method for the rapid determination of IgE binding sites (allergenic determinants) of proteins is reported. The method utilizes the epitope mapping kit (Geysen et al., 1984) to synthesize hexapeptides of an allergen of interest, followed by a biotin-avidin system to detect peptide-bound IgE. The technique allows rapid localisation of determinants from allergens of known sequence without the need to purify large amounts of allergen nor to generate peptides by cleavage of it. Using the results of the epitope mapping experiments a putative allergenic peptide containing 18 amino acid residues from the sequence of a wheat allergen was identified and synthesised on polyamide resin. Testing of this peptide by radioallergosorbent test (RAST) inhibition showed that it bound specific IgE in the sera of patients allergic to wheat.     

Pharmacodynamic studies with a specific alpha 2-adrenoceptor agonist (BHT-933) in man

We conducted pharmacodynamic studies in man with a specific alpha 2-adrenoceptor agonist BHT-933. The study involved nine male normotensive volunteers each of whom received BHT-933 5 mg or placebo in random order. BHT-933 significantly lowered systolic and diastolic blood pressure (BP) in supine and standing positions, the greatest effect occurring 3-4 h following drug administration. Supine values: placebo 116/73; BHT-933 99/64. Standing values: placebo 114/79; BHT-933 92/67. Heart rate was uninfluenced by BHT-933 even at the time of maximum fall in BP. Plasma noradrenaline concentration in the supine position was significantly reduced: placebo 2.5 +/- 0.8 nmol/L; BHT-933 1.7 +/- 0.6. The haemodynamic changes accompanying Valsalva's manoeuvre and cold pressor test were uninfluenced by BHT-933. All subjects experienced sedation and dry mouth following BHT-933 with a time course similar to that of the fall in BP. These results are consistent with an effect of BHT-933 on BP control through an action on alpha 2-receptors at the level of the brainstem.     

Permanent inflation of detachable balloons with a low-viscosity, hydrophilic polymerizing system

A polymer system was developed for use in permanent inflation of detachable balloons, to avoid long-term reliance on the integrity of balloon shells or valve mechanisms. This system is based on 2-hydroxy-ethyl methacrylate (HEMA) as the monomer, in combination with a cross-linking agent and a water-soluble curing system. The low-viscosity, hydrophilic mixture can be exchanged through a small-bore catheter into a detachable balloon and polymerizes in 40-60 minutes at body temperature. Partially polymerized HEMA can cause vascular occlusion; hence, careful timing of balloon detachment is required. The evolution of the radiographic appearance of HEMA-filled balloons is predictable. The balloons remain radiopaque on plain radiographs as long as the balloon shell and valve mechanisms are competent. After rupture of the shell or failure of the valve mechanism, the balloons become invisible on plain radiographs but remain hyperattenuating on computed tomography scans.