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Biomedical subjects

J R Marsden

Publications and source records attributed to J R Marsden.

At least 55 records · Page 3Linked to original sources

Drug acetylation and expression of lupus erythematosus.

Acetylator phenotype was measure in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls. Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D+SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators.

Acetylation↗

Antipyrine clearance and alpha 1-acid glycoprotein levels after isotretinoin.

Eight male subjects aged 18-24 years were treated with 0.5 mg of isotretinoin day-1 kg-1. After 4 weeks levels of cholesterol (P less than 0.05) and triglyceride (P less than 0.05) were increased and levels of high-density lipoprotein (HDL)-cholesterol were decreased (P less than 0.05). Concentrations of aspartate aminotransferase (P less than 0.01) and gamma-glutamyltranspeptidase (P less than 0.01) were higher after treatment; increased alkaline phosphatase and a reduction in bilirubin levels did not reach statistical significance. Values for thyroxine were reduced after isotretinoin and free thyroxine index was lower (P less than 0.01). Measurements of salivary clearance of antipyrine and levels of alpha 1-acid glycoprotein were lower after treatment but these differences did not reach statistical significance. The findings suggest that there is a small decrease in hepatic microsomal-enzyme activity after isotretinoin and that the unwanted effects on lipids, liver and thyroid function are unlikely to be due to hepatic microsomal-enzyme induction.

Acne Vulgaris↗

Evidence that method of use, dose and duration of treatment with benzoyl peroxide and tetracycline determines response of acne.

Treatment of acne prior to referral was recorded retrospectively in 72 patients alleged to have responded inadequately; 60% had used benzoyl peroxide (BP) but most applied it to lesions only. Although 86% had used tetracycline, most did not take it correctly for maximum absorption and took less than 1 g/day. Most patients used both drugs for less than three months. Eight-two patients referred because of inadequate response were treated with: (I) 5% benzoyl peroxide (BP) (23 patients); (II) 5% BP and 0.5 g/day oxytetracycline (OTC) (24 patients); (III) 5% BP and 1 g/day OTC (18 patients); (IV) 5% BP and 1.5 g/day OTC (17 patients). BP was applied incrementally from 30 min up to 8-10 hours daily to the entire area affected and OTC taken as a single morning dose. Median grade of severity (0-10 analogue scale) fell by 2 in Groups I and II (P less than 0.05), by 2.5 in Group III (P less than 0.05) and by 3 in Group IV (P less than 0.05); number of lesions fell by 56% +/- 7% (s.e.), (P less than 0.001) 70% +/- less than 10% (P less than 0.001), 75% +/- 8% (P less than 0.001) and 78% +/- 10% (P less than 0.001) respectively and treatment was well tolerated. Thus, although effective drugs are frequently prescribed in acne, method of use, dose and duration are likely to determine response.

Acne Vulgaris↗

Effects of isotretinoin on serum lipids and lipoproteins, liver and thyroid function.

Seven patients with severe rosacea were treated with 1 mg/kg per day isotretinoin for 12 wk. There were significant increases in serum triglyceride (p less than 0.001) and cholesterol (p less than 0.001). Triglyceride associated with very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) increased (p less than 0.01), cholesterol in VLDL and LDL increased (p less than 0.01), and levels of HDL cholesterol decreased (p less than 0.01). There were changes in indices of liver function, with increased levels of gamma-glutamyltransferase (GGT) (p less than 0.01), alkaline phosphatase (ALP) (p less than 0.01) and aspartate aminotransferase (AST) (p less than 0.01), and decreased bilirubin levels (p less than 0.05). Although levels of thyroxine and triiodothyronine were lower after treatment (p less than 0.05), there were no changes in basal levels of thyroid-stimulating hormone (TSH), luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and responses to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) were unchanged. These changes may partially be explained by induction of hepatic microsomal enzymes by isotretinoin.

Adult↗

Reduction of antipyrine clearance in psoriasis.

Antipyrine clearance was determined in 41 psoriatics and age-sex matched controls, using sequential measurements of salivary concentration. Antipyrine clearance and elimination rate constant were less in psoriatics (P less than 0.05) and apparent volumes of distribution were similar. These differences were greater between female psoriatics and controls (P less than 0.025; P less than 0.05) and the differences between male psoriatics and controls were not significant. Correlation of simultaneous measurements of saliva and plasma antipyrine concentration in six psoriatics and age-sex matched controls showed no differences between the two groups. We conclude that antipyrine clearance is reduced in psoriasis but the underlying mechanism is unclear.

Adolescent↗

Effect of low dose cyproterone acetate on the response of acne to isotretinoin.

Twenty-seven males with severe acne were treated for 12 weeks with 0.05 mg/kg/day isotretinoin (ten patients) or 5 mg daily cyproterone acetate (eight patients) or both drugs together in these doses (nine patients). With isotretinoin, the sebum excretion rate (SER) fell by 45% +/- 9% s.e.m. (P less than 0.0025), lesion count fell by 65% +/- 10% (P less than 0.0005) and median clinical 17% +/- 12% (NS) fall in SER, a 15% +/- 10% (NS) fall in lesion count and the median severity was unchanged. Patients unchanged. Patients treated with both drugs showed a 42% +/- 13% reduction in SER (P less than 0.005), a 68% +/- 11% decrease in lesion count (P less than 0.0005) and a decrease in median severity from 8 to 4 (P less than 0.01) which was no different from the response to isotretinoin alone. Isotretinoin increased serum cholesterol from 4.4 mmol/l +/- 0.3 s.e.m. to 4.7 mmol/l +/- 0.3 s.e.m. (P less than 0.01), serum triglyceride from 0.73 mmol/l +/- 0.07 s.e.m. to 0.96 mmol/l +/- 0.14 s.e.m. (P less than 0.05) and gamma-glutamyltransferase (GGT) from 15.9 i.u./l +/- 2.1 s.e.m. to 19.0 i.u./l +/- 2.4 s.e.m. (P less than 0.01). Comparison of the area under the concentration-time curve for triglyceride and high density lipoprotein (HDL)-cholesterol showed that the changes were smaller when isotretinoin was combined with cyproterone acetate. We conclude that the effect of isotretinoin in acne was not enhanced by the antiandrogen, but the increase in serum triglyceride and decrease in HDL-cholesterol produced by the retinoid were reduced by combination with the antiandrogen.

Acne Vulgaris↗

Measurement of the response of psoriasis to short-term application of anthralin.

Thirty-six patients with psoriasis were treated with short-term application of anthralin in three studies. (I) In thirteen patients 2% anthralin was applied daily to lesions on one arm for 60 min; (2) in ten patients 4% anthralin was applied daily to lesions on one-half of the body for 30 min; (3) in thirteen patients 2% anthralin was applied daily to lesions on one-half of the body for 30 min and the strength was increased to 4% and then 8% at intervals of 3 or more days, according to tolerance. Comparison was made with the response to conventional daily treatment with 0.05% to 1% anthralin. Progress was compared clinically by days to clearing, by measurements of plaque thickness with Harpenden calipers, by the frequency and severity of burning, and by patient preference. There was no significant difference in the times to clinical clearance between short-term and conventional anthralin treatments and the rate of decrease of plaque thickness was likewise similar. There was an excellent correspondence between time to reach half plaque thickness and the time for each plaque to clear clinically. There was increased burning with all the short-term treatments but the patients still preferred it. We conclude that short-term treatment with anthralin is as effective as continuous application, but that the increased burning is likely to limit its usefulness.

Administration, Topical↗

Effect of oral 13-cis-retinoic acid on serum lipids.

Serum lipid concentrations were measured in eighteen patients with severe acne before, during and after treatment with 0.8 mg/kg 13-cis-retinoic acid for 3 months. Cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations fell significantly during therapy. There were significant abnormalities of liver function and small decreases in indices of thyroid function. These changes had reverted to normal by 1 month after treatment. The data suggest that use of the drug in acne is likely to be limited by its toxicity.

Acne Vulgaris↗

Evidence for a cerebral cholinergic system and suggested pharmacological patterns of neural organization in the prostomium of the polychaete Nereis virens (SARS).

The histological visualization of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) on frozen sections of prostomia of Nereis virens indicate a concentration of cholinergic activity in the anterior brain. Components are probably sensory epithelial cells with cholinergic axons entering the brain in cephalic nerves and efferent cholinergic axons to prostomial muscle leaving the brain in the same nerves. There are also subepidermal cholinergic cells that may be second order motor neurons serving epidermal mucous cells. The smaller, second lobe of the corpora pedunculata and its associated vertical fibre tract are CAT(+) and appear continuous, on each side of the cerebral ganglion, with a dorsal and ventral longitudinal bundle of AChE(+) fibers. This system tapers to nothing at the level of the posterior eyes. There is a small AChE(+) component to each optic nerve and AChE is present in the nuchal epithelium. These observations are discussed in relation to earlier studies on aminergic and neurosecretory activity in the same ganglion.

Acetylcholinesterase↗

Uptake of tritium-labelled biogenic amines by the prostomium of the polychaete Nereis virens (Sars) (Annelida).

The uptake of tritium-labelled 5-HT, noradrenaline, 5-hydroxytrytophan, DOPA and dopamine by the cerebral ganglion and prostomial nervous system of the polychaete Nereis virens has been examined using radioautography at the level of the light microscope. Pronounced uptake of (3)H-5HT occurred in the antennal, palpal, tegumentary and nuchal nerves as well as in ganglionic nuclei 13, 14, 15, 16, 17, 20, 24 and 25, the mid-brain neuropile, the neurosecretory neuropil and the infracerebral organ; (3)H-NA uptake was observed in small cells in the prostomial epidermis, and the infracerebral organ; (3)H-dopamine only in one of two common types of epidermal mucus cells. Prostomial muscles labelled generally with (3)H-NA and at specific sites with (3)H-5HT. These observations support the concept of an efferent serotonergic system originating in several cerebral ganglionic nuclei and serving prostomial muscle and epidermis. Evidence for an afferent adrenergic system is less substantial. The role of dopamine remains obscure.

5-Hydroxytryptophan↗

An investigation into the enzyme histochemistry of adenocarcinomas of human large intestine and of the transitional epithelium immediately adjacent to them.

Histochemical enzymatic studies were performed on 30 freshly resected large bowel carcinomas, 30 samples of normal colonic epithelium, and six samples of the histologically normal epithelium (so-called transitional epithelium) immediately adjacent to a carcinoma. Five enzymes were studied: nicotine adenine dinucleotide tetrazolium reductase (NADH-TR), glucose-6-phosphate dehydrogenase, succinate dehydrogenase, monoamine oxidase, and acid phosphatase. QUANTITATIVE AND QUALITATIVE DIFFERENCES IN ENZYME ACTIVITY WERE OBSERVED BETWEEN NORMAL, TRANSITIONAL, AND CARCINOMATOUS MUCOSA AS FOLLOWS: monoamine oxidase activity was moderate in normal mucosa, high in transitional mucosa, and low in carcinoma. Succinate dehydrogenase activity was high in transitional mucosa and low or moderate in normal and carcinomatous mucosa. Glucose-6-phosphate dehydrogenase activity showed a gradation from low in normal mucosa to high in carcinoma while acid phosphatase showed the reverse of this pattern. The tetrazolium reductase activity was low or moderate in normal and transitional mucosa and high in carcinoma. These differences in enzyme activity and their possible clinical and metabolic significance are discussed.

Acid Phosphatase↗