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Biomedical subjects

H J Smith

Publications and source records attributed to H J Smith.

At least 73 records · Page 4Linked to original sources
PubMed1996

Contrast-enhanced MRI of rheumatic joint disease.

Early MR diagnosis of inflammatory rheumatic joint disease relies on the detection of the proliferating synovium. Several studies have shown that reliable visualization of the inflamed synovium is dependent upon the enhancement provided by intravenously injected paramagnetic contrast media. This presentation discusses the role of contrast-enhanced MRI in the assessment of inflammatory rheumatic joint disease. It is concluded that the method may aid in early diagnosis, and that it has a great potential in the assessment of disease severity and inflammatory activity.

Arthritis, Rheumatoid↗
PubMed1996

Synthesis and biological evaluation of 3-(prop-2-enyl)- and 3-(prop-2-ynyl)pyrrolidine-2,5-dione derivatives as potential aromatase inhibitors.

3-(4'-Aminophenyl)pyrrolidine-2,5-dione (WSP3), a known reversible inhibitor of P450 aromatase, was modified using molecular graphics and our model of reversible inhibitor and substrate binding to resemble 10 beta-prop-2-ynylestr-4-ene-3,17-dione (PED), a mechanism-based inactivator of the enzyme. The analogues prepared were 3-substituted 3-(prop-2-enyl) or 3-(prop-2-ynyl) pyrrolidine-2,5-diones and their N-alkyl derivatives. The reported compounds demonstrated no irreversible (time-dependent) inhibition of the human placental P450 aromatase enzyme. However, some reversible activity was seen in several of the 3-(prop-2-ynyl) compounds.

Aminoglutethimide↗
PubMed1996

A dapsone-induced blood dyscrasia in the mouse: evidence for the role of an active metabolite.

In the female mouse, dapsone (50-500 mg kg-1, p.o.) caused a dose-related methaemoglobinaemia which peaked at 0.5-1 h with recovery to baseline values occurring by 4 h. Cimetidine (100 mg kg-1, p.o.), a known inhibitor of several hepatic P450 isozymes administered 1 h before dapsone, prevented the methaemoglobinaemia. In-vitro, dapsone required activation by mouse hepatic microsomes to cause methaemoglobin formation in mouse erythrocytes and cytotoxicity to human mononuclear leucocytes. In both instances, the toxic effects were markedly reduced by cimetidine. Daily dosing of mice with dapsone (50 mg kg-1, p.o.) for 3 weeks induced a blood dyscrasia, characterized by a fall of platelet and white blood cell counts, which was inhibited by cimetidine (100 mg kg-1, p.o. daily). It is concluded that an active metabolite of dapsone arising from a P450-dependent pathway is involved in the genesis not only of the methaemoglobinaemia but also the blood dyscrasia arising from repeated administration of the drug in this species.

Animals↗
PubMed1996

Gadodiamide in renal transplant patients: effects on renal function and usefulness as a glomerular filtration rate marker.

Gadodiamide at a dose of 0.1 mmol/kg was administered intravenously to 10 renal transplanted patients with stable, impaired, or slowly deteriorating renal function (serum creatinine 194-362 mumol/l). The patients were referred for contrast medium enhanced magnetic resonance imaging to rule out possible graft circulation abnormalities. The excretion of gadodiamide in urine was prolonged as compared with healthy controls. After 120 h 92% of the injected dose was excreted in urine and only 0.4% in faeces. The plasma clearance of gadodiamide was 28.6 +/- (SD) 5.5 ml/min (n = 10), and the renal clearance (0-72 h) was 26.3 ml/min. The renal clearance of 125I-iothalamate for the same time period was 27.9 +/- 5.3 ml/min. Thus, gadodiamide is eliminated by glomerular filtration also in renal transplant patients with moderately to severe impaired renal function, and gadodiamide clearance may serve as an alternative marker for the determination of the glomerular filtration rate. Serum values of creatinine and beta(2)-microglobulin and creatinine clearance were unchanged by gadodiamide and neither was the urinary enzyme excretion significantly changed. These results suggest that the renal tolerance to gadodiamide is good also in renal transplant patients with impaired renal function.

Adult↗
PubMed1996

Cervicocranial artery dissection. Detection by Doppler ultrasound and MR angiography.

PURPOSE: To evaluate pulsed Doppler ultrasound and MR angiography (MRA) in the diagnosis of cervicocranial dissection. MATERIAL AND METHODS: Fourteen patients with cervicocranial artery dissection were examined over a 3-year period. Twelve patients had dissection of the extracranial part of the internal carotid artery, and 2 had vertebral artery dissection. All patients were examined with pulsed Doppler ultrasound. In addition, all patients had conventional angiography (n = 9) and/or MR imaging including MRA (n = 9). RESULTS: Doppler ultrasound disclosed unspecific abnormalities in 11 of 14 dissected vessels; 3 patients had false-negative Doppler findings. MRA showed vessel abnormalities in 9 of 9 patients; 2 vessels were occluded, and 7 vessels had changes typical of dissection (double lumen and/or string sign). Twelve patients had follow-up examinations with pulsed Doppler ultrasound (n = 12), conventional angiography (n = 3), and MRA/MR (n = 11). Follow-up Doppler showed complete or partial normalization in 6 of 9 patients, all confirmed by either angiography or MRA. CONCLUSION: Our findings suggest that Doppler ultrasound may be used in follow-up of pathologic Doppler findings in known dissections, and that MRA may replace angiography in the confirmative diagnosis of cervicocranial dissection.

Adult↗
PubMed1995

Monitoring of Dinitrotoluene and its metabolites in urine by spectrophotometry of their coupled aryldiazonium salts.

A rapid, accurate method was developed for monitoring employee absorption of dinitrotoluene (DNT). The method reduces DNT and its metabolites in urine to primary arylamines, diazotizes them with nitrous acid, then couples the diazo compounds with N-(1-Naphthyl)ethylenediamine, producing a colored complex. Spectrophotometric analysis of the colored complexes at 550 nm provides a measure of DNT absorption. The chemistry prevents interferences from all but primary arylamines and compounds reduced to primary arylamines. A six-month monitoring program of employees at a DNT manufacturing facility was conducted. Control samples from individuals not exposed to DNT were used to define an exposure indication level. The exposure indication level was used to correlate DNT exposure with job description or individual activity and was defined as apparent DNT and metabolite concentrations greater than 38 micrograms/ml. Group exposure also was indicated and associated with plant activity. Job description were ranked according to a rational evaluation of exposure potential and correlated well with monitoring data.

Case-Control Studies↗
PubMed1995

Metabolism of beclamide after a single oral dose in man: quantitative studies.

A simple reverse phase HPLC assay is described for the determination of the anticonvulsant compound, beclamide and its 3- and 4-hydroxyphenyl metabolites in urine. Following oral administration of 1 g beclamide to a panel of healthy volunteers, less than 0.4% of the dose was excreted unchanged in the 24-h urine and unconjugated 3- and 4-hydroxyphenyl metabolites were not detected. Based on examination of the urine after incubation with beta-glucuronidase and aryl sulphatase, it was found that these hydroxyl metabolites were excreted as both glucuronide and sulphate conjugates. For each metabolite the glucuronide was the major excretory product (approximately 10:1). The 24-h excretion of the combined conjugated metabolites was 7% (for the 3-hydroxy metabolite) and 24% (for the 4-hydroxy metabolite) of the dose. Approximately 22% of the administered dose of beclamide was excreted as hippuric acid. In view of the simplicity of assay, beclamide may be a useful tool substance with which to examine factors influencing the xenobiotic metabolic pathways of benzene ring hydroxylation and glucuronide and sulphate conjugation in man.

Administration, Oral↗
PubMed1994

Racemisation of drug enantiomers by benzylic proton abstraction at physiological pH.

The enantiomers of the aromatase inhibitors 3-(4-aminophenyl)-pyrrolidine-2,5-dione (WSP-3, II), its N-pentyl derivative (III), and the antifungal econazole (IV), all possessing a benzylic proton at the chiral centre, are rapidly racemised in vitro in phosphate buffer (0.01 M) at pH 7.4 and 23 degrees C with t 1/2 values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)-econazole is racemised after intraperitoneal injection with t 1/2 = 1.24h. The enantiomers of the antifungal 1-[(benzofuran-2-yl)-4-chlorophenylmethyl] imidazole (V) were stable at pH 7.4, attributable to steric hindrance to carbanion formation in the racemisation step.

Aniline Compounds↗
PubMed1994

Seven patients with respiratory infections due to Corynebacterium pseudodiphtheriticum.

Seven cases of lower respiratory tract infection due to Corynebacterium pseudodiphtheriticum are described. Lower respiratory tract infections with C. pseudodiphtheriticum in immunocompetent patients are usually associated with pre-existing chronic pulmonary disease, and are sometimes associated with endotracheal intubation. Antimicrobial susceptibility testing of these isolates showed uniform sensitivity to penicillin and variable results to erythromycin.

Aged↗
PubMed1994

Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database.

From December 1988 to April 1994, the extraction of 2,195 intravascular pacing leads from 1,299 patients was attempted at 193 centers. Indications were: infection (54%, including 10% septicemia), pacemaker reoperation with removal of nonfunctional or incompatible leads (40%), and other causes (6%). Extraction was attempted via the implant vein using locking stylets and dilator sheaths, via the femoral vein using snares, retrieval baskets, and sheaths, or via both approaches. Leads had been implanted for 0.2 months to 24 years (mean 56 months). At the conclusion of the intravascular procedure, 86.8% of the leads were completely removed, 7.5% were partially removed, and 5.7% were not removed. For physicians performing their first case, 12% of leads were not removed; for physicians who had performed more than 10 cases, only 2% of leads were not removed. Of the 189 leads where extraction attempts had previously failed, 75.1% were completely removed, 14.8% were partially removed, and 10.1% were not removed. Scar tissue increased in severity with implant duration, was a complicating factor, and was the main cause of failure to remove leads. Use of the femoral approach increased with implant duration (5% of leads implanted 12 months or less, 11% of leads 13 months to 3 years, 20% of leads 4-7 years, and 31% of leads 8-24 years), primarily because of increasingly abundant scarring and prior lead damage. Fatal and near fatal complications occurred in 2.5%, including 8 (0.6%) deaths (3 hemopericardium/tamponade, 1 hemothorax, 3 pulmonary embolus, 1 stroke).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Vanadium air pollution: a cause of malabsorption and immunosuppression in cattle.

An epidemiological investigation into an "illthrift" problem occurring on a dairy farm adjacent to an alloy-processing unit, established that the probable cause of the problem was chronic vanadium poisoning. The disease manifested initially in animals 4-18 months old which showed emaciation, chronic diarrhoea and, in some cases, rhinitis, conjunctivitis and recumbency followed by death. Post-mortem (n = 17) and clinical-pathology findings (n = 60) indicated that malabsorption and immunosuppression were the basis of the pathogenesis in affected animals. Eight months after the commencement of the investigation, adult cows began showing evidence of emaciation, reduced milk production and an apparent increase in the number of abortions, stillbirths and dystocias. Over a 2-year period, 134 surface-soil samples, 134 subsoil samples and 134 grass samples from the farm were analysed for various fractions of vanadium. Thirty-four of each of these samples were collected at different time intervals (autumn 1990, summer 1991 and winter 1991) and at varying distances and directions from the processing unit, in order to gauge the magnitude of the problem, and the distribution pattern of vanadium, and to identify possible seasonal trends. The remaining 100 of each of these samples were taken at 100-m intervals over an area of approximately 1,140,000 m2 directly adjacent to the processing unit so that concentration isolines for vanadium could be drawn and the source more conclusively identified. The levels of vanadium were found to be highest closest to the mine, and surface-soil levels were consistently higher than subsoil levels, suggesting aerial pollution, which was confirmed by air sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed1993

Inhibitors of enkephalin-degrading enzymes as potential therapeutic agents.

A limited number of enzymes such as membrane metalloendopeptidase (enkephalinase) and angiotensin converting enzyme appear to be involved in deactivation and modulation of circulatory regulatory peptides. Peptides such as the enkephalins are also involved in a large number of physiological processes. This multiplicity of physiological roles has made it difficult to establish the therapeutic role of enkephalin-degrading enzyme inhibitors. Other factors such as difficulty in quantification and thus measurement of processes involved in pain and mental illness have also hindered the process of establishing any therapeutic role of enkephalin-degrading enzyme inhibitors in these conditions. However, they have proved to be useful pharmacological 'tools'. The most likely therapeutic role at present appears to be in the treatment of cardiovascular disorders. As a 'profile' of pharmacological actions of enkephalin-degrading enzymes emerges, it is becoming apparent that bioavailability rather than a high degree of specificity or inhibitory potency may be the most important factor. This may be used to an advantage in future developments by the use of less specific or combined inhibitors in the form of prodrugs, designed to be active at specific sites such as the central nervous system.

Aminopeptidases↗
PubMed1993

Intravascular extraction of chronic pacemaker leads: efficacy and follow-up.

Extraction of chronic pacemaker leads has been recommended for infections, prevention of venous thrombosis, migration, and possible perforation. Success with constant traction techniques has been variable, and the cost and morbidity of open chest surgical procedures are prohibitive. Efficacy of a new system for lead extraction using intravascular techniques was analyzed. The system (Cook Pacemaker) uses a locking stylet, which is secured at the distal electrode by counterclockwise rotation to reinforce the lead and facilitate traction, and dilator sheaths that are used to free the lead from adhesions in the venous system. In a series of 56 patients (ages 19-88) who presented for lead extraction because of erosion (5), infection (14), lead replacement (35), or other (2), 86 leads were extracted. Thirty-two were atrial leads and 54 ventricular; 23 had active fixation and 63 passive. Average duration of implant was 58 +/- 42 months (range 1-264). Eighty-four leads were totally removed and two partially removed. For these two leads, the distal tip was not removed; in both cases the locking stylet was not secured at the distal electrode due to obstruction within the lead. Two patients developed arm edema following the procedure, which resolved with elevation. One patient developed a subclavian thrombosis, which resolved with warfarin anticoagulation. Four patients have expired due to unrelated causes. In conclusion, this intravascular approach for extraction of chronic leads is effective, and the procedure is safe when performed by experienced personnel.

Adult↗
PubMed1993

1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, a selective aromatase inhibitor: in vivo studies.

1-Pentyl, 1-hexyl and 1-heptyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, potent inhibitors of aromatase, lower oestrogen levels in PMSG-stimulated female rats in a comparable manner to the inhibitor aminoglutethimide (AG) used clinically for the treatment of breast cancer. Pharmacokinetic studies in the rat show t 1/2 values for the 1-hexyl compound and AG of 1.8 and 5.5 h respectively. In 4 tests for CNS-depressant activity the overall order of activity was AG > 1-heptyl = 1- hexyl >> 1-pentyl. The 1-pentyl compound has less tendency than AG to depress white cell and platelet counts in mice and overall is the drug candidate for further studies.

Aminoglutethimide↗