Duplex Doppler detection of intrarenal arteriovenous fistula and pseudoaneurysm.
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Biomedical subjects
Publications and source records attributed to K Harris.
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Although increased levels of specific IgE and/or IgG antibodies have been documented in individual cases of occupational asthma caused by common types of isocyanates (hexamethylene diisocyanate [HDI] and diphenylmethane diisocyanate [MDI]), the frequency among workers with occupational asthma is still unknown. The sera of 62/65 workers referred for specific inhalation challenges with isocyanates were analyzed for the presence of specific antibodies to the relevant isocyanate. Most workers (39, 63%) were exposed to HDI, some to MDI (17, 27%), and a few to toluene diisocyanate (six, 10%). Specific inhalation challenges were positive in 29 subjects, eliciting either immediate (seven), early late (two), late (13), or dual (seven) reactions. Specific inhalation challenges were more often positive in those subjects with increased nonspecific bronchial responsiveness. Twenty-nine subjects demonstrated increased levels of specific IgE and/or IgG antibodies to isocyanates in the absence of antibodies against human serum albumin (increased IgE only, no subject; IgG only, 20; both IgE and IgG, nine subjects). Although there was a loose association between the results of specific inhalation challenges and levels of specific IgE, the association was much better with the level of specific IgG. Indeed, 21 of the 29 subjects (72%) with positive challenges had increased levels of specific IgG, whereas 25 of the 33 subjects (76%) with negative challenges had normal levels of antibodies. The association was significant with both HDI and MDI. The levels of antibodies were not significantly associated with the type of temporal reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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The average number of nucleolar organiser regions per cell has previously been shown to correlate well with histological grading techniques for a variety of neoplasms in man, and may thus be of value as an aid to post-surgical prognosis. In this study 50 spontaneously arising, subcutaneous canine mast cell tumours were graded and the histological grade compared with the mean AgNOR count. For well differentiated neoplasms the mean count was 1.4 per cell compared with 6.3 for poorly differentiated neoplasms, while tumours of intermediate differentiation had a mean count of 3.2 per cell. Subsequent follow up studies revealed that the AgNOR count was an accurate prognostic indicator, 73% of dogs with a high mean count (greater than 4.9) being destroyed from tumour related disease compared with 33% with an intermediate count (1.7-4.8). No dog with a count of less than 1.7 has been destroyed because of tumour recurrence to date and the AgNOR count has proved to be a better and more objective prognostic indicator than either histological tumour grade or mitotic index. Since most dogs which develop recurrent mast cell tumours do so within 6 months of initial surgery, an assessment of the predictive value of AgNORs can be obtained more quickly in canine tumours than for comparable human neoplasms.
Cefuroxime axetil in a single daily dose of 250 mg for ten days was given to 75 women with symptoms of acute uncomplicated urinary tract infections. Fifty-nine women were found to have significant bacteriuria but one was excluded as urethral catheterization was required. The dose was taken at night with a milk drink. Ninety-five per cent of women had a clear urine during treatment. Compliance studies showed that antimicrobial activity was detectable in early morning urines up to 8-10 h after the dose. Post treatment, 93% of women were clear of their original infecting organism but five women had become reinfected with a different strain of Escherichia coli. At the six week follow up 98% of women were still clear although one further reinfection had occurred. The overall cure rate was 86%, including 11% reinfection. Adverse events developed in 17 (23%) of the 75 women with candida vaginitis (8) and diarrhoea (4) being most common. Cefuroxime axetil is a valuable therapy for the treatment of urinary tract infection particularly when due to beta-lactamase producing bacteria.
A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a Kab of 0.0135 min-1 and 0.0185 min-1 for i.m. and 0.0032 min-1 and 0.0074 min-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32-42%) and peak serum concentrations were much lower with s.c. than with i.m. (60-65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time (t1/2B) increased from 174.5 +/- 13 min for the 15 mg/kg dosage to 239 +/- 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.
Alterations in lipid metabolism occur in patients with chronic renal disease and in patients with the nephrotic syndrome and may have a role in the progression of renal disease in such patients. Evidence accumulated over the last few years indicates that increased ingestion of cholesterol accelerates the development of glomerulosclerosis in guinea pigs, rats and rabbits, and in rats with endogenous hyperlipidemia due to the nephrotic syndrome. Lowering the levels of serum lipids ameliorates the progression of renal disease in obese rats, rats with a remnant kidney and rats with the nephrotic syndrome produced by the aminonucleoside of puromycin. Changes in dietary fatty acids also influence the progression of renal disease. Several eicosanoids influence the progression of renal disease in experimental animals. Maneuvers that decrease the production of thromboxane A2 ameliorate renal disease in rats with a remnant kidney and in mice with lupus nephritis. Increasing the production of vasodilatory prostaglandins (PGE2, prostacyclin) seems to have a beneficial role in the progression of renal disease. The mechanisms by which dietary lipids and/or renal eicosanoids affect the progression of renal disease remain to be defined.
Sera collected from 1,102 individuals in 14 populations of the southwestern Pacific between 1956 and 1979 were tested by ELISA for antibodies to human T-cell leukemia virus type I (HTLV-I). Selected sera were also tested by particle agglutination and immunoblotting. Six of the populations had prevalences of antibodies greater than 4%, two populations had prevalences greater than 15%. Six populations had antibody prevalences of 2% or less. Three populations from the coast and northern islands of New Guinea had high prevalences of antibodies, while three New Guinea highland groups had virtually none. One population from the Solomon Islands had a high prevalence, while two others had very low prevalences. Two populations from small remote islands in Vanuatu both had high prevalences. Pacific sera did not neutralize a standard strain of virus readily neutralized by Japanese, European, and American sera. We conclude that infections with HTLV-I, some acquired more than 20 years ago, are widespread throughout the southwestern Pacific, even in several very isolated populations, although others have been spared. Some strains of HTLV-I in populations of the Pacific may have substantially different envelope proteins from prototype strains of America, Europe, and Japan.
Following ureteral obstruction there is a progressive fall in glomerular filtration rate (GFR) due to a reduction in single nephron glomerular filtration rate (SNGFR) and a reduced number of filtering nephrons. Renal plasma flow also declines after a transient, prostaglandin-dependent increase, due to afferent and efferent arteriolar vasoconstriction. The vasoactive hormones thromboxane A2 and angiotensin II are implicated in the pathogenesis of the vasoconstriction following ureteral obstruction and they also reduce the glomerular ultrafiltration coefficient by causing mesangial contraction. Ureteral obstruction also leads to profound changes in renal tubular cell function. These include altered sodium and water handling resulting in a post-obstructive diuresis and natriuresis and a failure to dilute or concentrate the urine. Potassium and divalent cation exchange is also affected, as is urinary acidification. Furthermore, the response of the tubule to hormones such as antidiuretic hormone and parathyroid hormone is impaired. The pathophysiology of these alterations in renal function is discussed.
Pharmacokinetic studies using a new oral quinolone ofloxacin were carried out in 12 healthy volunteers. The mean Cmax was 2.7 mg/l after the first dose of 200 mg ofloxacin rising to 3.4 mg/l after the seventh dose. The Tmax was between 1-2 h and the serum half life 5 h. Saliva concentrations matched serum levels but the absolute values were lower. Urinary concentrations ranged from 141 to 330 mg/l and the 12 h excretion was 62% after the seventh dose. Faecal concentrations were high and persisted for up to five days after the last dose. The major effect of ofloxacin on the faecal flora was the rapid and complete elimination of aerobic Gram-negative bacilli. Streptococci were generally increased but there was no change in the total anaerobic bacterial count. Pre-treatment composition of the faecal flora was re-established between 3 and 26 days after the last dose. Ofloxacin was well tolerated by the volunteers and only two complained of significant side effects, gastrointestinal disturbance and insomnia. Ofloxacin is a valuable addition to the range of antimicrobial agents available for the oral treatment of bacterial infection.
In order to obtain steroid-independent probes for human progesterone receptor (PR), the A [88-93 kilodalton (kDa)] and B (109-119 kDa) forms of PR from T47D human breast cancer cells were partially purified and used to generate a series of 14 monoclonal antibodies. Initially, unoccupied PR was isolated from cytosol extracts by steroid affinity chromatography, followed by chromatography on diethylaminoethyl Bio-Gel. The partially pure (3-15%) PR consisted of two steroid-binding components that migrated at 89 kDa and 109 kDa in reducing sodium dodecyl sulfate gels after being photoaffinity labeled with the synthetic progestin [3H]R5020. Two unique monoclonal antibodies to PR were derived from a male Lewis rat immunized with this material. One of these antibodies (JU601) was coupled to Sepharose 4B and used to purify T47D nuclear PR for additional immunizations. Highly purified (30-70%) PR migrated as 93 kDa and 119 kDa progestin-binding proteins in sodium dodecyl sulfate gels. In all, thirteen monoclonal antibodies were obtained that recognized epitopes shared by both receptor forms. One mouse immunoglobulin G (KC146) was completely specific for the larger B form. Interestingly, the epitope for this antibody was present on all PRs tested, including the B form of PR from chicken oviduct, whereas nine other antibodies recognized only human PR and the remaining four cross reacted with rabbit PR. With the exception of the JU145 and JU601 rat immunoglobulin Ms, all antibodies appeared to be completely specific for the A or B forms of PR. Each recognized the cytosol and nuclear forms of occupied as well as unoccupied PR. Although the relationship between B and A was not established, it is clear that an amino-terminal region of B is not present in A, and that a significant portion of A and B are either identical or very similar in amino acid sequence.
We describe a new clinical laboratory instrument, the IMx, used to automate immunoassay testing in the clinical laboratory. The IMx incorporates a novel technology called Microparticle capture Enzyme ImmunoAssay (MEIA) for assays of high-molecular-mass analytes, and fluorescence polarization immunoassay (FPIA) for hapten assays. A front-surface fluorometer is used to quantify the enzymatic generation of fluorescent product at a rate proportional to the concentration of the analyte in an MEIA, and a fluorescence polarization optical system is used to quantify results in an FPIA. The microprocessor-based instrument uses a robotic arm with two degrees of freedom and a rotating carousel to process the samples for assay. One assay can be done on each of 24 patients' specimens in 30 to 40 min with "walk-away" automation. Calibration curves are stable for at least two weeks. Instrument control involves software-labeled "command keys," a numeric keypad, and an interactive display. Results are output to a thermal printer or computer interface.
In order to compare the effects of Diazemuls and midazolam on arterial oxygen saturation during upper gastrointestinal endoscopy, 120 patients were randomly allocated to receive Diazemuls, midazolam, or normal saline. Endoscopy was performed by one consultant or one of four residents. Arterial oxygen saturation was monitored continuously during endoscopy by means of a Biox III pulse oximeter and ear probe. Oxygen saturation fell during endoscopy in all three groups, but no significant differences between the groups were detected at any stage of the procedure. When all groups were combined, there was significantly less desaturation when the consultant performed the endoscopy, and he was also significantly faster in carrying out endoscopy than the residents in each group. When an inexperienced resident was compared with one with at least 6 months of experience, there were significant differences in degree of desaturation, lowest value during endoscopy and tolerance score. It is suggested that the patient at risk of hypoxemia should, if possible, be endoscoped by an experienced endoscopist.
We investigated the properties of the novel dorsal root ganglion (DRG) hybrid cell line F-11 to see how closely these cells resembled normal DRG cells. Under normal growth conditions, F-11 cells appeared to contain several short neurite-like processes. However, these cells could also be grown under conditions in which they showed a much more extensive neuronal morphology, exhibiting many long neurites. Several differentiated features of DRG cells were present on F-11 cells. These included the presence of delta-opioid receptors, receptors for prostaglandins and bradykinin, and dihydropyridine-sensitive calcium channels. F-11 cells also synthesized and released a substance P-like compound, as determined by immunoreactivity. Both the number of bradykinin receptors and the voltage-sensitive calcium influx increased on cell differentiation. Opioid agonists (delta-specificity) were found to decrease cyclic AMP levels in F-11 cells in a naloxone- and pertussis toxin-reversible fashion. Bradykinin stimulated the synthesis of inositol-1,4-bisphosphate and inositol-1,4,5-trisphosphate. Ca2+ channel agonists stimulated voltage-sensitive Ca2+ influx in a dose-dependent, stereospecific manner, whereas Ca2+ channel antagonists inhibited Ca2+ influx. F-11 cells should, therefore, prove useful as models for authentic DRG neurons.
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Previous studies have demonstrated that protein S is required for optimal activated protein C-mediated inactivation of Factor Va on the surface of either the platelet or phospholipid vesicles. In this report we demonstrate assembly of the activated protein C-protein S complex on the surface of cultured bovine aortic endothelial cells. Endothelial cell surface acceleration of Factor Va inactivation by activated protein C required the presence of protein S. Kinetic studies indicated that the rate of Factor Va inactivation was half-maximal at a protein S concentration of 0.2 nM and an activated protein C concentration of 0.05 nM. Binding of 125I-activated protein C to endothelial cell monolayers was absolutely dependent on the presence of protein S. At saturating levels of protein S, activated protein C binding was saturable with Kd = 0.04 nM. In contrast, specific, time-dependent, and saturable binding of 125I-protein S to endothelium occurred in the absence of activated protein C. Addition of activated protein C increased the affinity of protein S from Kd = 11 nM to 0.2 nM, but did not change the number of molecules bound per cell at saturation (85,000 molecules/cell). These studies suggest that activated protein C increases the affinity of protein S for pre-existing sites on the endothelial cell surface. The close correlation between the parameters of protein S-activated protein C binding to endothelium and Factor Va inactivation supports the concept that it is bound protein S and activated protein C that are the active species. Formation of functional activated protein C-protein S complexes thus occurs effectively on the endothelial cell surface and represents a new addition to the list of vessel wall anticoagulant properties.
The protein C-protein S anticoagulant pathway is closely linked to the endothelium. In this paper the synthesis and release of the vitamin K-dependent coagulation factor protein S is demonstrated. Western blotting, after SDS PAGE of Triton X-100 extracts of bovine aortic endothelial cells grown in serum-free medium, demonstrated the presence of protein S. A single major band was observed at Mr approximately 75,000, closely migrating with protein S purified from plasma absent from cells treated with cycloheximide. Metabolic labeling of endothelial cells with [35S]methionine confirmed de novo synthesis of protein S. Using a radioimmunoassay, endothelium was found to release 180 fmol/10(5) cells per 24 h and contain 44 fmol/10(5) cells of protein S antigen. Protein S released from endothelium was functionally active and could promote activated protein C-mediated factor Va inactivation on the endothelial cell surface. Warfarin decreased secretion of protein S antigen by greater than 90% and increased intracellular accumulation by almost twofold. Morphological studies demonstrated intracellular protein S was in the Golgi complex, concentrated at the trans face, rough endoplasmic reticulum, lysosomes, and in vesicles at the periphery. In contrast, protein S was not found in vascular fibroblasts or smooth muscle cells. A pool of intracellular protein S could be released rapidly by the calcium ionophore A23187 (5 microM). This effect was dependent on the presence of calcium in the culture medium and could be blocked by LaCl3, which suggests that cytosolic calcium flux may be responsible for protein S release. These results demonstrate that endothelial cells, but not the subendothelial cells of the vessel wall, can synthesize and release protein S, which indicates a new mechanism by which the inner lining of the vessel wall can contribute to the prevention of thrombotic events.