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Biomedical subjects

M Palmer

Publications and source records attributed to M Palmer.

At least 199 records · Page 11Linked to original sources
PubMed1985

Food-induced changes in theophylline absorption from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle.

Food-induced changes in absorption from two controlled-release formulations of theophylline (Uniphyl tablets [Purdue Frederick Co.] and Theo-Dur Sprinkle [Key Pharmaceuticals, Inc.]) were studied in healthy male nonsmokers. Although the two forms exhibited a theophylline in vitro dissolution rate that was independent of changes in pH from 1 to 8, they showed substantial but opposite food-induced absorption changes. In a 12-subject, three-way, single-dose, randomized, crossover study the bioavailability of theophylline relative to immediate-release aminophylline tablets increased from 53% +/- 23% (means +/- SD) to 96% +/- 46% when Uniphyl (two 400 mg tablets) was taken under fasting and nonfasting (high fat content meal) conditions, respectively. On the other hand, in a separate six-subject, two-way, randomized, crossover study, food reduced the bioavailability of theophylline from Theo-Dur Sprinkle: Theophylline bioavailability in the nonfasting state was only 53% +/- 9% that in the fasting state.

Absorption↗
PubMed1985

Ascertainment of vital status through the National Death Index and the Social Security Administration.

Ascertainment of the vital status of individuals is of central importance to epidemiologic studies which monitor mortality as an end point. Utilizing identifying information collected in 1973-1974, the Hypertension Detection and Follow-up Program, a prospective, multicenter study, followed 25,362 individuals to determine eight-year mortality. In the most recent follow-up, there were 617 individuals whose vital status was not known. Available identifying information on these and on all 1,322 participants known to have died in 1979-1981 was submitted to the National Death Index (NDI) for possible confirmation of vital status. A subset of individuals who had Social Security numbers (490 lost to follow-up and 1,154 known deaths) was also submitted to the Social Security Administration (SSA). The NDI correctly identified 87.0% of the known deaths. Of the 1,154 known deaths (those with known Social Security numbers) submitted to both agencies, the NDI identified 93.1% and the SSA 83.6%. Significant variations by race and sex were noted in the identification rates, in part because of Social Security number discrepancies. False matches through the NDI matching process occurred for 10.4% of the known deaths. In the more restrictive SSA search, only 0.5% false matches resulted. For those lost to follow-up, vital status was ascertained in 57.1%. This paper describes the relative efficacy and attributes of the use of these systems to ascertain vital status.

Aged↗
PubMed1985

Identical RT1 class II molecules are expressed by rat RT1m and RT1c haplotypes.

The RT1m haplotype of MNR rats has been suggested to be a recombinant RT1 haplotype inheriting RT1.A (class I) alleles from RT1a (DA) and RT1.B (class II) alleles from RT1c (AUG). Additional serologic and biochemical assays, however, have suggested that RT1m and RT1c share a single identical RT1.B molecule, although differing in the expression of the second RT1.B molecule. To resolve this contradiction, RT1.B class II molecules, comparable to I-A and I-E molecules in mice, expressed by the RT1c and RT1m haplotypes were immunoprecipitated by cross-reactive mouse anti-Ia antibodies and were compared by two-dimensional gel electrophoresis and by high pressure liquid chromatographic separation of tryptic peptides. Respective subunits expressed by the two haplotypes co-migrate on two-dimensional gels and have identical tryptic peptide maps. The results at the protein level were confirmed at the DNA level by Southern blot analysis of MNR and AUG genomic DNA. Identical restriction fragments associated with the RT1m and RT1c haplotypes hybridized with each of the DC1 beta, DR alpha, and DR beta cDNA probes. The results at both the protein and DNA levels suggest that the RT1m and RT1c haplotypes share identical expressed alleles at the RT1.Ba, RT1.Bb, RT1.Bc, and RT1.Bd loci.

Animals↗
PubMed1984

Differential effects of phencyclidine upon hippocampal complex-spike and theta neurons.

The effects of local application of phencyclidine (PCP) upon hippocampal CA1 neurons were investigated in urethane-anesthetized rats. Hippocampal neurons were classified on the basis of extracellularly recorded action potential duration as either complex-spike or theta cells prior to PCP administration. PCP depressed spontaneous firing of 46 of 48 complex-spike cells, but excited 12 of 13 theta neurons. This result demonstrates that hippocampal complex-spike and theta neurons may be differentiated of theta neurons were greatly attenuated or absent in rats pretreated with DSP4, a neurotoxin which selectively destroys noradrenergic pathways. This latter finding lends additional support to the hypothesis that the effects of locally applied PCP are mediated via noradrenergic mechanisms.

Animals↗
PubMed1984

Enkephalin immunoreactivity in iris nerves: distribution in normal and grafted irides, persistence and enhanced fluorescence after denervations.

The morphology and distribution of nerve fibers showing enkephalin-like immunoreactivity was studied in rat and mouse iris whole mounts. In adult rat, a relatively dense network of varicose fibers was seen throughout the iris. Individual, long, usually smooth fibers were observed running together with non-fluorescent fibers in bundles. Positive nerve fibers were also seen in the ciliary body and the choroid membrane. The fluorescence intensity was normally low. No enkephalin-positive fibers were detected in adult mouse iris. Extirpation or lesioning either one or all the three ganglia known to supply the rat iris with nerve fibers, the superior cervical, the ciliary and the trigeminal ganglia, caused no detectable decrease in amount of enkephalin-positive fibers. However, in irides grafted to the anterior eye chamber of adult recipients, no enkephalin-positive fibers could be observed 2-12 days postoperatively, strongly suggesting that degeneration of these fibers had occurred. When iris grafts were left longer in the eye, nerve fibers with enkephalin-like immunoreactivity reappeared. An increased fluorescence intensity was observed both in the ipsilateral and contralateral iris following extirpation or lesioning all three ganglia and in the ipsilateral iris after extirpation of the ciliary ganglion. Three days after a systemic injection of capsaicin, which causes a permanent disappearance of substance P fibers, the same phenomenon was often observed. This raises the possibility of an interaction between the enkephalin-positive and the substance P fiber systems in the iris.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Survival of leptospires in commercial blood culture systems.

Laboratory diagnosis of leptospirosis depends on the serological findings and, if possible, the isolation of the organisms. During the period 1981-1982 there were 40 blood cultures submitted from serologically positive patients and a successful isolation rate of only 12% was attained. Correct media, method of collection of suspect blood and laboratory technique all contribute to the successful isolation of the organism. Because of the low isolation rate an investigation was undertaken of various blood culturing systems used in Great Britain. Results obtained showed that certain blood culture media were able to maintain the organism better and therefore increase the isolation rates of leptospira. Factors affecting the isolation rate are presented.

Blood↗
PubMed1984

Some toxic effects of lead, other metals and antibacterial agents on the nervous system--animal experiment models.

Modern man is chronically exposed to lead levels in the biosphere, several times higher than the natural level that once existed. There is much concern about the possible adverse effects of this population-wide low-level lead exposure, particularly on the developing organism, where the central nervous system may be a primary target for lead. We have developed animal test systems which permit temporal and spatial discrimination of possible effects of lead and other potentially neurotoxic agents in the environment on the developing central nervous system, as well as on different types of peripheral nerves in the adult individual. In one experimental design, defined areas of the fetal rat brain are grafted to the anterior chamber of the eye of adult rat recipients which are exposed to lead (1% PbAc in drinking water). Such grafts will become vascularized from the host iris and continue their development in oculo. Thus the grafted brain tissue and the host brain will share circulation and therefore be exposed to exactly the same amounts of lead simultaneously. Studies of cerebellar grafts revealed that although there was a normal gross cytological development in the presence of lead, there was a severe, permanent impairment of the spontaneous discharge rates of the grafted Purkinje neurons as observed with electrophysiological techniques long after cessation of the lead treatment. The host Purkinje neurons were not affected. A similar, although less dramatic, impairment of cerebellar function could then be demonstrated in intact animals when newborn rats were given lead (8 mg PbAc/kg i.p.) during the first 20 days of life and then studied as adults. In other areas of the fetal central nervous system grafted to the eye, lead caused disturbed growth (substantia nigra, cortex cerebri). A screening technique for potentially harmful effects on autonomic and sensory nerve terminals in adult rats makes use of intraocular injections of agents to be tested. Morphological and histochemical changes of the innervation apparatus of the iris are then studied in iris whole-mount preparations. Lead causes an adrenergic hyperinnervation of the iris. Computer-based image analysis revealed severe degenerative effects by hexachlorophene and chlorhexidine. These studies demonstrate the usefulness of the intraocular grafts and the intraocular injection technique and the need to apply both structural and functional techniques in order to detect possible neurotoxic actions of xenobiotics. The techniques have revealed hitherto unknown toxic actions of lead on cerebellar function.

Adrenergic Fibers↗
PubMed1983

A prospective randomized trial of vagotomy in chronic duodenal ulceration: 4-year follow-up.

A total of 153 patients (124 male and 29 female) with uncomplicated chronic duodenal ulceration were studied in a prospective, randomized trial of proximal gastric vagotomy (PGV) and truncal vagotomy and pyloroplasty (TVP), conducted in four Manchester hospitals. Of these, 137 patients have now been followed up for 2.5 to 5.5 (mean 4.1) yr. There have been 15 (21 per cent) recurrent ulcers following PGV compared with 5 (7.5 per cent) after TVP (P less than 0.05). A satisfactory functional result was obtained in 82 per cent of patients after TVP compared with 73 per cent following PGV and there was little difference between the groups with regard to the incidence of dumping, heartburn and vomiting. There was significantly more diarrhoea following TVP (13 per cent) compared to PGV (1.4 per cent) but this represented only a minor clinical problem.

Adult↗
PubMed1983

Trophic effects of brain areas on the developing cerebral cortex: II. Electrophysiology of intraocular grafts.

Electrophysiological correlates of locus coeruleus-induced growth stimulation in rat cortical grafts homologously transplanted to the anterior chamber of the eye were studied. Neurons in growth-stimulated grafts manifested a slow sustained spontaneous discharge similar to that found in rat cortex in situ. Local administration of glutamate markedly augmented this discharge. In contrast, neurons from nonstimulated grafts fired in high frequency bursts separated by long pauses, and this discharge was comparatively insensitive to glutamate. Poststimulus inhibition after local stimulation of the transplant surface was readily observed in the growth-stimulated grafts, but absent in all non-stimulated grafts tested. Moreover, superfusion of picrotoxin, which antagonizes GABA-mediated inhibitory pathways, reversibly converted the growth-stimulated graft discharge pattern into one characteristic of non-stimulated grafts. Taken together with the data in the preceding paper, the results demonstrate the importance of extrinsic inputs for functional development of neuronal circuits within neocortex.

Acetylcholine↗
PubMed1983

Evidence for extensive polymorphism of class I genes in the rat major histocompatibility complex (RT1).

The major histocompatibility complex of the rat (RT1) has been poorly characterized with respect to the number, linkage, and polymorphism of class I genes. To estimate the number of class I RT1 genes and the relative extent of their polymorphism, we performed Southern blot analysis with liver DNA from rat strains expressing eight RT1 haplotypes. After digestion with EcoRI and BamHI, the DNA was separated on agarose gels, blotted onto nitrocellulose, and hybridized with mouse H-2 cDNA probes, pH-2III and pH-2IIa. Ten to 20 EcoRI and 13 to 20 BamHI bands hybridized with pH-2III and pH-2IIa; restriction fragment length patterns were observed to be highly polymorphic. The restriction fragments associated with different RT1 haplotypes differed by 17-70%; this range is similar to the differences observed between mouse H-2 haplotypes. The same restriction fragment pattern was observed in DNA from three different rat strains sharing the same RT1 allele, confirming that the patterns were RT1-associated. Further, the RT1l and RT1lvl haplotypes, which differ at a single previously identified RT1-linked locus, were associated with EcoRI restriction pattern differences of 39-50%, confirming the supposition that RT1 class I genes identified by previous serological and T-cell-mediated assays have identified only a minority of the actual number of RT1-linked class I genes. In summary, the results reported in this communication demonstrate that the RT1 complex encompasses a large family of highly polymorphic class I genes similar to the H-2 and HL-A complexes of mouse and man.

Alleles↗
PubMed1983

Cerebellar Purkinje neuron hypoexcitability induced by chronic perinatal lead exposure.

The effects of perinatal lead administration on developing rat brain were studied by using cerebellar grafts in oculo. With 1% lead acetate in the drinking water, little change was seen in the histological organization of the graft. In marked contrast, virtually all Purkinje cell spontaneous discharge was absent in these grafts. This was seen even though 4-5 months had elapsed between the recording and the cessation of lead treatment. There was no alteration in electrophysiological properties of transplant Purkinje cells from sodium acetate-treated animals. Moreover, host in situ cerebellar Purkinje cells in both groups of animals discharged normally. These data indicate that lead administration, to elicit blood levels of 450-550 micrograms/liter, produces a long-lasting selective electrophysiological deficit in developing brain in oculo.

Action Potentials↗
PubMed1983

Randomized trial of elective highly selective or truncal vagotomy in chronic duodenal ulceration.

Between 1973 and 1976, 153 patients (124 men, 29 women) with uncomplicated, chronic, duodenal ulcer were entered into a prospective randomized trial of highly selective vagotomy (HSV) or truncal vagotomy and pyloroplasty (TVP). The study was conducted in four Manchester hospitals and the operations were performed by consultants or chief registrars. The follow-up was conducted by personal interview using a standardized questionnaire. The medical gastroenterologist did not know which type of operation the patient had had. The patients who had symptoms were referred back to the surgeon who performed the operation. The clinical laboratory and follow-up data were analysed by computer. There were no operative deaths. Three patients died from unrelated causes, 13 were lost to follow-up; 137 (89.5%) were followed up for a mean of 4.1 years (range from 2.5 to 5.5 years). A modified Visick grading was used to assess the results of surgery. The outcome was good in 82% after TVP and 73% after HSV. This difference and those in the incidences of early or late postprandial dumping, bilious vomiting, weight loss, anemia and heartburn were not significant. Diarrhea was more frequent after TVP (13.4%) than after HSV (1.4%); although the difference was significant (p less than 0.025), this complaint did not present a serious clinical problem. Ulcers recurred in 15 (21.4%) patients following HSV and in 5 (7.5%) after TVP; this difference was statistically significant (p less than 0.05).

Adult↗
PubMed1982

Intermittent high-dose cyclophosphamide with and without prednisolone: a study of the relationships between toxicity, response and survival in metastatic lung cancer.

Fifty-seven patients with metastatic lung carcinoma were treated with either high-dose cyclophosphamide (Cy) alone or with a combination of high dose Cy and prednisolone (Pred) 100 mg/m2 orally daily for two days. The Cy was given IV on three occasions, at 1.5 g/m2, 2.5 g/m2 and 3.5 g/m2 with three-week intervals between courses. The overall response rate was 57% (18% CR), a median survival of 24 weeks (range, 6--130) for Cy alone, and 24% (3% CR), a median of 14 weeks (range, 1--94) for Cy + Pred. Patients with small cell carcinoma given Cy alone had a 69% response rate (19% CR), a median survival of seven months, and with non-small cell pathologic conditions 42% (16% CR), a median survival of 16 weeks. Performance scores and survival were better for responding patients. Addition of Pred did not improve the therapeutic efficacy of high dose Cy or ameliorate toxicity. No marked or unexpected toxicity was observed with the high-dose Cy regimen. The blood counts had returned to normal by three weeks in the great majority of patients. A short course of high-dose Cy was not associated with unacceptable side effects and the therapeutic results obtained were superior to those described for Cy at conventional dosage. High-dose Cy is of value to patients with metastatic lung cancer, and the incorporation of the regimen into chemotherapeutic combinations could be advantageous.

Adult↗