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Biomedical subjects

R H Palmer

Publications and source records attributed to R H Palmer.

18 recordsLinked to original sources
PubMed1992

Mutation of the casein kinase II phosphorylation site abolishes the anti-proliferative activity of p53.

The p53 tumour suppressor protein is phosphorylated by several protein kinases, including casein kinase II. In order to understand the functional significance of phosphorylation by casein kinase II, we have introduced mutations at serine 386 in mouse p53, the residue phosphorylated by this kinase, and investigated their effects on the ability of p53 to arrest cell growth. Replacement of serine 386 by alanine led to loss of growth suppressor activity, while aspartic acid at this position partially retained suppressor function. These data suggest that the anti-proliferative activity of p53 is activated by phosphorylation at serine 386, and establish a direct link between the covalent modification of a growth suppressor protein and regulation of its activity in mammalian cells.

3T3 Cells↗
PubMed1992

Principles of bone healing and biomechanics of external skeletal fixation.

External skeletal fixation is being used to treat an increasing number of orthopedic conditions in veterinary medicine. Study of the variables affecting the biomechanics of external fixation and bone healing is vital if patient morbidity is to be minimized. These are reviewed and incorporated into strategies that can be applied to decision making using external fixation in the clinical setting.

Animals↗
PubMed1992

Phosphorylation of the p53 tumour-suppressor protein at three N-terminal sites by a novel casein kinase I-like enzyme.

Wild-type mouse p53, expressed in Escherichia coli, was phosphorylated by highly purified casein kinase I (CKI) from rabbit muscle. The major site of phosphorylation in the p53 was identified as serine 6, which is known to be phosphorylated in vivo. Serines 4 and 9 were also phosphorylated. To determine whether CKI is likely to be a physiological p53 kinase, SV3T3 cell lysates were fractionated on a Mono Q column and assayed for p53 kinase and casein kinase activities. Four p53 kinase activities were detected, one of which co-purified with CKI activity. This p53 kinase (designated PK270) further co-purified with CKI on sucrose gradients and had a native molecular weight, like CKI, in the range of 35,000-45,000. However, PK270 was separated from the bulk of CKI activity on a phosvitin-Sepharose affinity column, and was therefore likely to be a CKI-related kinase. In support of these conclusions, phosphorylation of p53, by both CKI and PK270, was inhibited by a peptide corresponding to a consensus CKI target sequence, but not by a non-specific peptide. Moreover, phosphopeptide analyses of p53 phosphorylated by CKI or by PK270 gave similar results, indicating that these two kinases phosphorylate the same sites in p53.

3T3 Cells↗
PubMed1991

Neurologic manifestations of trypanosomiasis in a dog.

A 13-month-old Doberman Pinscher was evaluated because of slowly progressive paraparesis and signs of depression. The dog had temporal, supraspinatus, and infraspinatus muscle atrophy, bilateral enophthalmos, superficial inguinal lymphadenopathy, tachycardia with pulse deficits, and lesions of active and inactive chorioretinitis. Neurologic abnormalities included hyperreflexic patellar reflexes, lack of conscious proprioception, signs of superficial pain in the hind limbs, and depressed hopping reflexes in the forelimbs. Cranial nerve abnormalities included decreased sensation in the left nostril and a delayed gag reflex. Results of cerebrospinal fluid analysis were characteristic of nonsuppurative inflammation. A diagnosis of multifocal neurologic disease was made. The dog did not have serum titers for fungal diseases, canine distemper, Ehrlichia canis infection, borreliosis, Rocky Mountain spotted fever, or toxoplasmosis. The dog did not respond to various antimicrobial treatments, and only slightly responded to corticosteroid treatment. The dog died during an anesthetic procedure. The postmortem diagnosis of Trypanosoma cruzi infection (canine Chagas disease) was made on identification of the amastigote form of the organism in sections of brain, spinal cord, and myocardium.

Animals↗
PubMed1991

Variance components and their implications for statistical information in medical data.

We discuss general issues concerning the design and analysis of medical experiments involving repeated measures or hierarchical groupings of subjects within larger study units. Depending on the types of questions being investigated, the correlations induced by clustering can have dramatic impact on the effective sample size. The unique aspects of such experiments must be accounted for during analysis and during interpretation of the results. We illustrate these issues by using a variance components model to investigate the role of leadership in medical practice.

Ambulatory Care↗
PubMed1991

Effects of various concomitant medications on gastric alcohol dehydrogenase and the first-pass metabolism of ethanol.

Inhibition of gastric alcohol dehydrogenase (ADH) has been shown to enhance alcohol absorption in man under certain circumstances. To determine whether various medications might affect alcohol absorption, we screened 18 compounds for an effect on ADH. Salicylic acid, acetaminophen, propranolol, ethacrynic acid, and three H2-receptor antagonists all inhibited rat gastric ADH in vitro, indicating that several commonly used medications have the potential to enhance alcohol absorption. Of these, cimetidine, ranitidine, and nizatidine were studied further to define their effect on alcohol absorption in man and to assess the clinical relevance of the effect. Both ranitidine and nizatidine enhanced the absorption of small doses of alcohol (0.15 g/kg) in the morning by 63% and 64% and increased Cmax by 48% and 54% respectively (p less than 0.001), effects similar to those reported by others for cimetidine. The effect of ranitidine given before dinner was greatly attenuated with increases in Cmax of 8% (NS) and AUC of 21% (p = 0.02). Cimetidine 800 mg hs did not affect the absorption of 0.15 g/kg alcohol given in the evening, and cimetidine 400 mg bid decreased absorption by 14% (p = 0.11). Cimetidine 300 mg qid had no effect on larger doses of alcohol given at dinner. We conclude that many commonly used medications affect gastric ADH, but that the increase in the actual amount of alcohol absorbed is quite small, and demonstrable only under special conditions.

Acetaminophen↗
PubMed1990

Maintenance therapy of duodenal ulcer with H2-receptor antagonists--a meta-analysis.

A theoretical basis for similar recurrence rates among H2-receptor antagonists exists based on recent concepts of ulcer recurrence, ulcer healing and suppression of nocturnal gastric acidity. In order to compare H2-receptor antagonists in the maintenance therapy of duodenal ulcer, a meta-analysis was carried out using 29 studies in the literature that met strict criteria. When the results of the placebo-controlled studies were expressed as odds ratios, a technique used to minimize differences in protocol design and patient populations among studies, cimetidine, ranitidine, famotidine and nizatidine were all found to be superior to placebo to approximately the same extent. Odds ratios (and 95% confidence limits) for the recurrences in the pooled studies were cimetidine 0.22 (0.18-0.28), ranitidine 0.23 (0.18-0.30), famotidine 0.28-0.31 and nizatidine 0.36. These reflected similar 1-year recurrence rates of 24.9% (n = 530) for 400 mg cimetidine nocte, 22.4 (n = 508) for 150 mg ranitidine nocte, 28.0% (n = 371) for 20 mg or 40 mg famotidine nocte, and 21.8% (n = 261) for 150 mg nizatidine nocte. In studies to compare cimetidine and ranitidine directly, the odds ratio (and 95% confidence limits) was 0.64 (0.48-0.86). However, for two studies done by a single protocol, the odds ratio of 0.51 (0.35-0.75) tended to differ from the odds ratio of 0.85 (0.54-1.33) for six other studies (P = 0.09). These reflected recurrence rates for cimetidine and ranitidine of 28.3% and 16.8% (two studies) and 23.3% and 20.6% (six studies) respectively.

Cimetidine↗
PubMed1979

Individual and institutional variables which may serve as indicators of quality of medical care.

This article is a critical review of empiric studies, in the medical care literature of the past two decades, that investigated associations between characteristics of physicians and medical care institutions and some measure of the quality of medical care given by them. The intention is to identify those characteristics of physicians and medical care institutions which can be considered the best indicators of the quality of performance to be expected, given the present state of knowledge. The analysis discusses 18 such characteristics but derives a list of 14 which appear to be the best choice of indicators on which further research might focus. It would be possible to design a survey instrument based on these characteristics, which, if upheld by empiric testing, could serve as a crude assessment tool for third parties needing to make quality comparisons between medical care institutions.

Age Factors↗
PubMed1978

Prevalence of gallstones in hyperlipidemia and incidence during treatment with clofibrate and/or cholestyramine.

The present study provides no evidence that the prevalence of gallstones is increased in patients with hyperlipidemia. During the first year of treatment with clofibrate, the incidence of new gallstones appears to increase 8-fold. Cholestyramine, in doses of 16 g per day, does not seem to increase the incidence of stones, either when given alone or with clofibrate. Further studies on the cumulative risk of clofibrate and the long-term effect of clofibrate on biliary lipid composition are necessary to adequately define the risk/benefit ratio of this medication--with or without bile acid sequestrants. It is highly desirable to ascertain whether the concurrent administration of agents such as chenodeoxycholic or ursodeoxycholic acids could beneficially affect bile lipid composition and hence protect against gallstone formation during the initial period of clofibrate treatment.

Cholelithiasis↗
PubMed1977

Biliary lipid metabolism in the pregnant baboon.

The serum cholesterol value, bile acid pool size and kinetics as well as lipid composition of gallbladder bile have been studied in seven baboons during nine pregnancies. During pregnancy, the per cent decrease in the average serum cholesterol value ranged from 25.6 to 74.4 per cent, mean 54.5 +/- 14.3 per cent, compared with that of antepartum averages. In seven of the nine pregnancies, chenodeoxycholic acid pool size decreased in the range of 40.1 to 86.6 per cent. In two pregnancies, the pool size of this bile acid was essentially unchanged. Total bile acid pool size also decreased from a mean of 990 +/- 260 milligrams antepartum to 520 +/- 200 milligrams in the third trimester, p less than 0.01. With regard to the cholesterol, phospholipid and bile salt content of gallbladder bile, cholesterol value decreased from an antepartum mean of 19.1 +/- 3.9 to 14.1 +/- 4.5 micromoles per milliliter in the third trimester. As a consequence, the lithogenic index of gallbladder bile decreased during pregnancy. The changes in chenodeoxycholic and total bile acid pool size are qualitatively similar to those reported by other investigators following the administration of estrogens to both baboons and other animal species. In the pregnant baboon, the decrease in pool size and in synthesis rate of bile acids is accompanied by a decrease in the cholesterol content of gallbladder bile. These changes in the lipid content of gallbladder bile are reflected in a decrease in the mean lithogenic index. These data suggest that the baboon may be an inappropriate model for studies of the relationship of pregnancy to cholesterol cholelithiasis in humans. In the baboon, both serum and biliary cholesterol values decrease during pregnancy. In humans, serum cholesterol levels increase during pregnancy. If the content of biliary cholesterol is a reflection of the serum concentration of this lipid, as has been suggested in recent studies, human bile may be more lithogenic during pregnancy. Additional studies are necessary to define the role of gallbladder contractility and bile stasis to gallstone formation during pregnancy.

Animals↗
PubMedDate not supplied

Distraction osteogenesis using modified external fixation devices in five dogs.

Distraction osteogenesis was used to treat five dogs with limb deformities or limb shortening. The affected bones underwent osteotomy, and modified external fixators were attached. Complications included pin loosening, implant breakage, and soft-tissue contracture. Adequate limb length was attained in all cases, but clinical results varied from poor to excellent. Two dogs were not lame after the procedure, two dogs had improved function but were still lame, and one dog had complications necessitating amputation.

Animals↗