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Biomedical subjects

M D Stephens

Publications and source records attributed to M D Stephens.

At least 19 recordsLinked to original sources
PubMed2000

Bioaccumulation of polychlorinated biphenyls in ranid frogs and northern water snakes from a hazardous waste site and a contaminated watershed.

Livers of bullfrogs (Rana catesbeiana) from a polychlorinated biphenyl (PCB) contaminated watershed and hazardous waste site located in Pickens County, South Carolina, contained significantly higher concentrations of PCBs (2.33 and 2.26 ppm, respectively) than those from a reference site (0.05 ppm). Green frogs (R. clamitans) from the two contaminated sites also accumulated higher levels of PCBs (2.37 and 3.88 ppm, respectively) than those from the reference site (0.02 ppm). No temporal variation was observed in PCB concentrations of bullfrogs or green frogs from the contaminated sites between 1992 and 1993. Levels of PCBs in the livers of northern water snakes (Nerodia sipedon) were significantly higher in snakes from the contaminated watershed (13.70 ppm) than in those from the waste site (2.29 ppm) and two reference sites (2.50 and 1.23 ppm). When compared to frogs, significantly higher bioaccumulation occurred in water snakes from the contaminated watershed. No significant differences in PCB levels were found with respect to sex or body size (snout-vent length (SVL) or body mass) for frogs or snakes. PCBs were detected also in eggs of both frogs and snakes. Results of this study provide baseline data and document the bioaccumulation of PCB residues in frog and snake tissues; however, the significance of these tissue residues to reproduction, survival, growth/development, and population dynamics in contaminated habitats is unknown.

Animals↗
PubMed1999

Interim report on the incidence of visual field defects in patients on long term vigabatrin therapy.

The incidence was determined of visual field defects in patients in the Prescription-Event Monitoring (PEM) study, treated for > or =6 months with the antiepileptic drug vigabatrin. Questionnaires were sent to the general practitioners of the 7228 patients in the PEM study, treated with vigabatrin for > or =6 months, to ascertain whether any serious adverse events, including changes in vision, had occurred. Ophthalmologists were asked to give the results of the perimetry tests and their opinion of the cause of the visual field defect for those patients referred to them. 6793 (94%) of the 7228 questionnaires were returned. 5090 (75%) contained clinical data. 328 patients were deceased. Seventy seven cases identified from the 4762 surviving patients, are being followed up with ophthalmologists. To date, 2 weeks after posting, 12 cases of visual field defect have been confirmed by formal perimetry tests. Ten of these 12 were considered to be probably or possibly related to vigabatrin use, giving an incidence of 2.0 per 1000 patients compared with 0.4 per 1000 patients in the original PEM cohort. These interim results show a substantial increase in the incidence of visual field defects associated with long term use of vigabatrin and demonstrate that PEM can be used to assess long latency adverse events.

Journal Article↗
PubMed1996

The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients.

OBJECTIVE: To examine the safety of finasteride as used in general medical practice to treat benign prostatic hypertrophy (BPH). PATIENTS AND METHODS: Information was collected on 14,772 patients who were included in an observational cohort study conducted using Prescription-Event Monitoring. RESULTS: Finasteride was reported to have been effective in 60% of the patients in whom an opinion on efficacy was recorded. Impotence or ejaculatory failure was reported in 2.1% of the patients, decreased libido in 1% and gynaecomastia and related conditions in 0.4%. Impotence was the most frequent reason for stopping treatment with finasteride and was the most commonly reported adverse reaction to the drug. Of the patients included in the elderly cohort involved in this study, 819 (5.5%) died; none of these deaths was attributed to finasteride. CONCLUSION: Impotence or ejaculatory failure, decreased libido and gynaecomastia in a small proportion of patients were associated with the use of finasteride. The results of this study strongly suggest that this drug is acceptably safe when used in accordance with the current prescribing information.

Adolescent↗
PubMed1991

The methodology of safety data in clinical trials.

Only Type A adverse drug reactions are likely to be detected during the pre-marketing clinical trial programme. The collection of adverse events may be by spontaneous reporting, a standard general question, a checklist, a self-answering questionnaire or a quality of life questionnaire. From these one needs to differentiate the adverse reactions due to the experimental drug from the ordinary every-day minor events occurring in healthy individuals, the adverse events relation to the target disease, the adverse events related to concurrent illnesses, the adverse reactions due to concomitant therapy and adverse events engendered by the comparator drugs or placebo. It is important to realise that the patients on the experimental drug may be infected with adverse reactions by the patients on the comparator drug. A post-treatment visit enables the doctor to check the laboratory investigations from the last visit whilst on treatment, any withdrawal symptoms from the drug, delayed adverse drug reactions, the response to dechallenge of any adverse reaction and arrange for follow-up of any problems or rechallenge. (Ref. 10).

Clinical Trials as Topic↗
PubMed1990

Phenotypic modulation in sub-populations of human articular chondrocytes in vitro.

Human articular cartilage has been separated into surface (approx. 15% of tissue depth) and deep zones (remaining tissue) and the constituent chondrocytes released by enzymic digestion. Subsequent culture either as a low density monolayer or as a suspension over agarose revealed distinct morphological and synthetic behaviour in the two populations. Whilst in monolayer these morphological differences disappeared with time in culture, over agarose they remained. Surface zone cells formed two types of cell cluster; one that was highly cellular with little extracellular matrix, and the other less frequent, which formed copious amounts of fibrillar matrix. Both types of cluster were surrounded by a layer of flattened chondrocytes. In contrast, deep cells formed a single cluster type that lacked a surrounding cell layer, but formed large amounts of sparse cartilage-like matrix and comprised morphologically typical chondrocytes. In monolayer, both populations gradually ceased to synthesise cartilage matrix components with the exception of link protein. In suspension, whilst the chondrogenic phenotype per se was preserved, there was, nevertheless, a loss in qualitative synthetic heterogeneity, which exists between surface and deep cells, that was not accompanied by changes in the differential rate of 35S incorporation into proteoglycan. Under these conditions, surface cells that normally do not synthesise keratan sulphate initiated de novo synthesis of this glycosaminoglycan. Consequently, it appears that the observed modulation in synthetic ability of the cell sub-populations is independent of the cluster morphology, which, once established, remains constant throughout the culture period.

Cartilage, Articular↗
PubMed1986

Frequency and directionality of gene conversion events involving the CYC7-H3 mutation in Saccharomyces cerevisiae.

The CYC7-H3 mutation is a 5-kb deletion that causes overproduction of iso-2 cytochrome c. Unlike most mutations in yeast, the CYC7-H3 mutation is preferentially lost when it is involved in a gene conversion event. We have shown that cloned copies of CYC7-H3 DNA that are inserted into the yeast genome are associated with a high frequency of recombination and aberrant segregation events. Since parity in conversion frequency was observed when the extensive insertion/deletion heterozygosity at this locus was eliminated, we conclude that the CYC7-H3 sequences are inherently capable of acting as donors or recipients in gene conversion events, although they are unlikely to act as donors when they are located opposite a large heterology. DNA sequence comparisons revealed similarities between the CYC7-H3 junction region and the 2-micron circle DNA region that is involved in site-specific recombination.

Chromosome Deletion↗
PubMed1986

Drug-induced piloerection in man: an alpha 1-adrenoceptor agonist effect?

The physiology of piloerection is described and clinical experience is discussed. The objective and subjective evidence for drug-induced piloerection by a number of drugs is given and, where it is known, their pharmacological mechanism is described. The results are considered in relation to the hypothesis that drug-induced piloerection is only produced by drugs with alpha 1-adrenoceptor agonist activity. For those drugs without the latter activity where piloerection is supported only by subjective evidence it is suggested that objective evidence should be sought. The fact that there is no objective evidence that the classical alpha 1-adrenoceptor agonist, phenylephrine, produces piloerection is found surprising and it is suggested that such evidence should be sought. If it is found that phenylephrine does not produce piloerection, then the possibility of the existence of a further alpha-agonist subgroup needs to be considered.

Adrenergic alpha-Agonists↗
PubMed1980

Comparison of labetalol and propranolol in hypertension.

1 Labetalol has been compared with propranolol in a double-blind, double-dummy study of 24 patients with mild or moderate essential hypertension. 2 Two patients were unable to tolerate propranolol and five labetalol, because of symptom side effects; this difference was not significant (P greater than 0.1). 3 On a self-administered questionnaire, labetalol was associated with a greater number of side effects per patient than propranolol, but no individual side effect was significantly more common with either drug. 4 There was no difference in the number of spontaneously reported side effects between the two drugs. 5 Both drugs impaired pulmonary function, but propranolol caused a greater reduction than labetalol after 8 weeks of treatment. 6 We conclude that labetalol and propranolol are similarly effective and acceptable to the patient.

Adult↗
PubMed1979

A long-term study of labetalol in general practice.

1 Forty-one patients with mild to moderate hypertension have been treated with labetalol for up to 5 years. 2 Mean BP before treatment was 180/107 mm Hg, after 2--3 yr treatment was 136/81 mmHg and after 5 yr was 136/74 mmHg. 3 One patient developed a licheniform rash and two patients have died of myocardial infarction. No other side-effects, not already observed in a previously reported double-blind trial, have emerged.

Adult↗
PubMed1975

A sensitive method for the comparative bioassay of nonsteroidal anti-inflammatory compounds in adjuvant-induced primary inflammation in the rat.

A method for the comparative bioassay of nonsteroidal anti-inflammatory agents is presented which exploits the early inflammation induced by injection of adjuvant into the plantar surface of a hind paw of the rat. The inflammation reaches a peak on the 4th postinjection day. Daily treatment with nonsteroidal anti-inflammatory agents reduces paw volumes and the associated impairment of body growth with optimal improvement on the 4th postinjection day. In this model, phenylbutazone has shown significant activity at doses as low at 1.33 mg/kg/day. Statistically valid comparative assays conducted at dose levels equivalent to or below those used in human therapy yield potency ratios with relatively narrow confidence limits. Potencies relative to phenylbutazone for inhibiting primary adjuvant-induced inflammation are: aminopyrine, 0.066 (0.36-0.11)95%; aspirin, 0.087 (0.039-0.19)95%; mefenamic acid, 0.98 (0.64-1.6)95%; flufenamic acid, 13 (7.4-26)95%; meclofenamic acid, 23(16-33)95%; and indomethacin, 53 (35-82) 95%. Ancillary and sometimes quantitative information is also provided by the improvement in well being of the animals as reflected in body weight changes with treatment.

Aminopyrine↗
PubMed1975

Comparative activities, tolerances and safety of nonsteroidal anti-inflammatory agents in rats.

Relative anti-inflammatory potencies of aspirin, phenylbutazone, indomethacin, three fenamates and several other nonsteroidal anti-inflammatory agents were obtained in several laboratory models of acute and chronic inflammation. Relative toxicities and ulcerogenicities were determined in rats of the same source, strain and sex. The acute ulcerogenic assay measures the minimal irritation potential of these agents and leads to a sensitive index of the safety of such compounds when compared with their therapeutic potencies. By these criteria, meclofenamic acid is a highly potent, acceptably safe and exceptionally well tolerated anti-inflammatory-antipyretic agent in rats when compared with other such drugs.

Analgesics↗