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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 181 records · Page 10Linked to original sources
PubMed1987

The manager dilemma.

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Administrative Personnel↗
PubMed1986

Monoamine receptor sensitivity changes following chronic administration of MDL 72394, a site-directed inhibitor of monoamine oxidase.

(E)-beta-Fluoromethylene-m-tyrosine (MDL 72394) is not per se an inhibitor of monoamine oxidase (MAO) but is a substrate of aromatic L-amino acid decarboxylase (AADC) which liberates the potent MAO inhibitor (E)-beta-fluoromethylene-m-tyramine (MDL 72392). When co-administered to animals with the peripherally selective AADC inhibitor, carbidopa, MDL 72394 inhibited MAO selectively in the brain. Chronic (14 days plus 3 days withdrawal) administration of 0.5 mg/kg per day p.o. MDL 72394, 0.1 mg/kg per day p.o. MDL 72394 combined with 10 mg/kg per day p.o. carbidopa or 50 mg/kg per day p.o. pargyline produced equivalent inhibition of rat brain MAO and decreased the binding of [3H]clonidine and [3H]RX 781094 to the alpha 2-adrenoceptor and of [3H]dihydroalprenolol to the beta-adrenoceptor without changing binding of [3H]prazosin to the alpha 1-adrenoceptor. The locomotor depressant effect of clonidine was attenuated without attenuation of the hypotensive effect in rats treated chronically with the MAO inhibitors. Neither the sensitivity of the alpha 2-autoreceptor nor of the alpha 2-heteroreceptor was decreased in brain slices. However, the sensitivity of adenylate cyclase to activation by both noradrenaline and isoprenaline was significantly reduced. The number of 5-HT2 and 5-HT1A binding sites was decreased: the 5-HT1B binding sites remained unchanged. The effect of chronic MAO inhibitor treatment on 5-HT1A receptors was associated with a decrease in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin and the decrease in 5-HT2 binding was related to a small reduction in the sensitivity of the inositol phosphate system to stimulation by 5-HT. The lack of effect of chronic MAO treatment on the 5-HT autoreceptor measured in cortical slices corresponded to a lack of effect on the 5-HT1B binding site except that chronic administration of pargyline produced a small but significant decrease in 5-HT autoreceptor sensitivity. Overall, the data show that chronic administration of MDL 72394 has a profile of effects on central monoamine receptor binding and function similar to that seen following chronic administration of a number of clinically effective antidepressants.

Adenylyl Cyclases↗
PubMed1986

Compliance of pediatric and adolescent cancer patients.

Compliance with self-administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age, 6.85 years) and 40 parents were extensively interviewed at 2 weeks, 20 weeks, and 50 weeks post-diagnosis. The results of self-reported compliance were corroborated by serum bioassay of the prescribed medications. A significant correlation between the age of patient and compliance with chemotherapeutic agents and nonchemotherapeutic medications was found (P less than 0.05 and P less than 0.02, respectively), with adolescent patients being compliant less often. Over the course of therapy, compliance among patients decreased, but not significantly. A significant negative correlation was found between compliance and the number of children in the family. Compliers and noncompliers did differ significantly in how well they understood instructions concerning how to take their medication (P = 0.04). No significant correlations between compliance and stage of the disease, number or type of drugs used, complexity of the regimen, degree of satisfaction with information given to the patient, understanding of disease, treatment, or belief in medication efficacy were found. The main reasons given for noncompliance were forgetfulness, busy schedules, and nonavailability of medication. More compliers than noncompliers were in agreement with their parents regarding who was responsible for the administration of the medication. Compliance is a complex and multifaceted issue which interrelates with a large number of medical and social factors.

Administration, Oral↗
PubMed1986

Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial.

Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Human peripheral monocytes express putative receptors for neuroexcitatory amino acids.

Human peripheral mononuclear cells responded chemotactically to 4-carboxyl-L-glutamic acid. The maximal chemotactic response occurred at 0.1 nM. No chemotactic response was found with neutrophils or fetal bovine fibroblasts. Glutamic acid, a neuroexcitatory dicarboxylic amino acid and the parent compound of 4-carboxyglutamic acid, did not stimulate chemotaxis in any of the cells tested. However, it functioned as an antagonist to 4-carboxyglutamic acid (ED50 approximately 2 pM; ED100 approximately 10 pM). In contrast to the lack of response to glutamic acid, its dicarboxylic cyclic analogue, kainic acid, excited a chemotactic response in mononuclear cells. The data suggest that mononuclear phagocytes have receptors for dicarboxylic neuroexcitatory amino acids, and we speculate that 4-carboxyglutamic acid, a tricarboxylic acid, may have a previously unrecognized role as a neuroexcitatory amino acid.

1-Carboxyglutamic Acid↗
PubMed1983

Weight gain and movement patterns of very low birthweight babies nursed on lambswool.

34 very low birthweight babies (mean 1143 g) in incubators were randomly assigned to be continuously nursed on lambswool (n = 17) or ordinary cotton sheets (n = 17). The weight gain for the periods when babies were well was significantly larger for the wool group, 22.7 g/day vs 18.6 g/day for cotton control (p less than 0.02). The overall weight gain (which included weight change during periods of illness) revealed a similar picture in favour of the wool group, 21.5 g/day vs 18.2 g/day (p less than 0.05). Movement patterns for the two groups showed no differences, but for all babies a strong correlation was noted between moving and lying suspine (p less than 0.001), having eyes open (p less than 0.001), a cooler incubator (p less than 0.01), and faster weight gain (p less than 0.01). Lambswool seems to have advantages over cotton sheets as a bedding material for very low birth weight babies.

Animals↗
PubMed1983

Precordial electrocardiographic mapping in the identification of patients with left main stem narrowing.

This study was designed to determine if exercise testing using 16-lead precordial mapping can be used to identify patients with left main stem narrowing. In a group of 235 consecutive patients undergoing coronary angiography there were 35 patients with left main stem narrowing. The patients with left main stem disease differed from the others in that not only did they develop extensive S-T segment depression, but more specifically these changes occupied a characteristic position high on the precordium above the usual site of the precordial leads of the 12-lead electrocardiogram. This finding was then tested prospectively in a second group of 100 patients. Fourteen of the 100 patients had left main stem narrowing; the sensitivity and specificity of S- T segment changes high on the precordium in identifying patients with left main stem disease were 82 and 84% respectively. Thus precordial mapping and exercise testing is valuable in the diagnosis of patients with left main stem narrowing. The technique is simple and inexpensive and provides data not available using the conventional precordial leads of the 12-lead electrocardiogram.

Adult↗
PubMed1983

Dose-response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings.

Clinical response and plasma pharmacokinetics were studied in 20 rheumatoid patients receiving three dosages of ibuprofen. There was a significant response to 1600 mg daily of ibuprofen by all three clinical measurements but increasing the daily dosage to 2400 mg produced no overall increase in response. The AUC increased with increasing daily drug dosages from 800 to 2400 mg daily and the dose normalised AUC fell by 15% over the same dosage range. The fraction of ibuprofen not bound to plasma proteins increased with increasing dosage and may contribute to the fall in the dose normalised AUC. There was a considerably inter-individual variation in the AUC. There was no significant correlation between AUC and clinical response as measured by articular index and there was a weakly significant correlation between AUC and clinical response as measured by a visual analogue pain index. Pharmacokinetic variables probably account for only a small part of the inter-individual variation in response of rheumatoid patients treated with increasing dosages of the non-steroidal, anti-inflammatory drug ibuprofen.

Adult↗
PubMed1983

Action of (S)-10-hydroxycamptothecin on P388 leukemia and distribution of the drug in mice.

As an inhibitor of the growth of P388 leukemia in mice, (S)-10-hydroxycamptothecin (OPT) was as potent as the parent compound camptothecin (CPT). Incorporation of thymidine into DNA was the parameter most sensitive to OPT in vitro (ED50 approximately 4 micrograms/ml), but incorporation of cytidine into RNA and of acetate into lipids was also reduced significantly in the presence of the drug. The cytofluorometric profile suggested suppression of the S and G2/M phases. The distribution of OPT in mice at 2 and 24 hours after ip injection (10 mg/kg) was essentially similar to that of CPT, with the exception of a somewhat greater concentration of CPT in the liver. In their pharmacology, OPT and CPT appear to be very similar, despite reports that the hydroxy derivative is less toxic.

Animals↗
PubMed1982

Effect of anthelmintic treatment on the milk yield of dairy cows in England, Scotland and Wales.

One hundred and twenty dairy herds collaborated in a trial to determine the effect on milk yield of anthelmintic treatment given at calving. Cows and heifers were divided into five groups. Three were each given a different anthelmintic: thiabendazole, fenbendazole or levamisole. One group was given a placebo and the fifth was untreated. Analysis of data from 9000 lactations showed a treatment effect just significant at the 5 per cent level, of 42 kg milk, 1.8 kg fat and 1.4 kg protein. There was no evidence that the three anthelmintics differed in their effect on yield. The effect of treatment was not greater in heifers than in cows, nor was there a difference between spring and autumn calvers. There was no indication that the effect of treatment was markedly greater in some herds than others and it was not related to periparturient faecal egg count.

Animals↗