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Biomedical subjects

D Davis

Publications and source records attributed to D Davis.

At least 145 records · Page 8Linked to original sources
PubMed1993

Heart transplantation for tumor.

Unresectable cardiac tumors, although unusual, are often rapidly fatal. A 31-year-old woman presented with a large tumor arising from the left ventricle and causing symptoms of a constrictive cardiomyopathy. After evaluation with echocardiography, angiography, and computed tomography, an exploration was carried out to confirm the extent of disease. Orthotopic heart transplantation was subsequently performed when a donor organ became available. She is now alive and disease-free 12 months after transplantation.

Adult↗
PubMed1993

Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli.

Colonization Factor Antigen (CFA/II) from enterotoxigenic Escherichia coli (ETEC) prepared under good manufacturing practices (GMP) was successfully incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA) polymer microspheres (BPM) under GMP and found to be safe and immunogenic when administered intraduodenally to rabbits. Following vaccination, Peyer's patch cells responded by lymphocyte proliferation to in vitro challenge with CFA/II. Also, B cells secreting specific anti-CFA/II antibodies were found in spleens following vaccination. No pathological changes were found following total necropsies of ten rabbits vaccinated with CFA/II BPM. Sixty-three per cent of the CFA/II BPM were between 5 and 10 microns diameter by volume particle size distribution; 1.17% protein content; 2.15% moisture; < 0.01% acetonitrile; 1.6% heptane; 22 non-pathogenic bacteria and three fungi per 1 mg protein dose; and passed the general safety test. We conclude that the CFA/II BPM oral vaccine is immunogenic and safe to begin a Phase I clinical safety study following Investigational New Drug approval.

Administration, Oral↗
PubMed1993

"Academic" CME and the social contract.

The term academic continuing medical education (CME) is defined and explored from the perspective of forces that have made its usage necessary. These forces include the new understandings of the place, impact, and scope of CME, and, in particular, the increasing entrepreneurial interests in the field, unrelated to the improvement of physicians' competence or performance, or to health care outcomes. In addition to principles of CME provision promulgated by the Accreditation Council of CME, and those of ethical CME providers, academic CME implies the critical appraisal of the providers' activities, the creation of new knowledge about how physicians learn and change, and the dissemination of information based on such knowledge. Finally, the nature of academic CME providers is discussed, and the potential role of CME in fostering the social contract between the medical professional and society is explored.

Clinical Competence↗
PubMed1993

Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope.

Antibodies have been raised against a synthetic peptide (IRDKIQKENALFRNL) containing a neutralizing epitope within the second variable region of the human immunodeficiency virus type 1 (HIV-1) SF2 strain external envelope glycoprotein (gp120) and also against equivalent peptides of the HIV-1 LAI, RF and MN isolates. The resulting antisera cross-react with heterologous peptides but binding to heterologous recombinant gp120 is more restricted. Antisera to HIV-1 SF2, RF and MN are able to neutralize homologous virus. Some cross-neutralization is also observed, but a consensus peptide failed to induce neutralizing antibodies to any of the isolates studied. Antibodies to the V2 and V3 epitopes give a higher neutralization index when acting together than when the individual sera are used alone. Antibodies induced in natural infection bind to two sets of hexamers within the region encompassed by the 15-mer peptide, and the response to these can differ between infected individuals and within the same host over time.

Amino Acid Sequence↗
PubMed1993

Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans.

During dynamic exercise, blood flow to exercising muscle is closely matched to metabolic demands. This is made possible by metabolic vasodilation, vasoconstriction in inactive vascular beds, and a rise in cardiac output. The sympathetic nervous system plays an important role in regulating this exercise response. In this study, we used steady-state infusions of tritiated norepinephrine ([3H]NE) to determine the magnitude and time course of the arterial NE spillover response to sustained upright bicycle exercise at low (n = 11) and moderate-to-high (n = 14) exercise intensity (25 and 65% of maximum work load, respectively) in normal young subjects. In addition, we sought to examine whether exercise was associated with a change in NE clearance. During 30 min of low-level exercise, arterial NE spillover increased from 1.45 +/- 0.13 to 3.14 +/- 0.30 nmol.min-1 x m-2 (P < 0.01) and appeared to plateau at 20-30 min of exercise; NE clearance remained unchanged. During 20 min of moderate-to-high-intensity exercise, we found a substantial and progressive rise of arterial NE spillover from 2.15 +/- 0.27 to 13.52 +/- 1.62 nmol.min-1 x m-2 (P < 0.01). NE clearance decreased from 0.91 +/- 0.05 to 0.80 +/- 0.05 l.min-1 x m-2 (P < 0.05). These data suggest that, during dynamic exercise, sympathetic nervous system activity is related to exercise intensity, and there appears to be an interaction between the effects of exercise intensity and duration on NE spillover. In addition, at moderate-to-high exercise intensity, a small decrease of NE clearance contributes to the rise in plasma NE.

Adult↗
PubMed1993

The advanced clinical information system: physician-focused.

The U.S. health care system is being forced to change because of intense demands for better quality, decreased cost, and better service. These demands are driving the implementation of health-oriented computer technologies that will fundamentally change the practice of medicine. These technologies will enable physicians to find new opportunities to improve quality and reduce cost.

Attitude to Computers↗
PubMed1993

Toward successful compliance with JCAHO standard NC.1.

Recommendations resulting from a JCAHO survey can be a true blessing as they force nursing departments to assess critically their professional practice and documentation systems. Systematic preparation, begun at least two years prior to the survey, includes Nursing Administration, a Nursing Documentation Task Force and all staff nurses. Educational consultants assigned to each unit bring nurses up-to-date on nursing process and nursing diagnosis. Mock surveys and cross-training in chart review prepare staff nurses for confident participation in the accreditation process.

Accreditation↗
PubMed1992

Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids.

Cerebral deposition of the beta-amyloid peptide (A beta) is an invariant feature of Alzheimer's disease. Since the original isolation and characterization of A beta (ref. 1) and the subsequent cloning of its precursor protein, no direct evidence for the actual production of discrete A beta has been reported. Here we investigate whether A beta is present in human biological fluids using antibodies specific for an epitope within A beta that spans the site of normal constitutive cleavage. These antibodies were used to construct a sandwich-type enzyme-linked immunosorbent assay that detects A beta in cerebrospinal fluid, plasma and conditioned medium of human mixed-brain cells grown in vitro (see also ref. 14). By affinity chromatography, we have purified and sequenced A beta and a novel A beta fragment from human cerebrospinal fluid and conditioned medium of human mixed-brain cell cultures. These findings demonstrate that A beta is produced and released both in vivo and in vitro. These observations offer new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of A beta.

Alzheimer Disease↗
PubMed1992

Analysis of the p21 ras system during development of meiotic competence in Xenopus laevis oocytes.

The ability of Xenopus oocytes to undergo insulin- or insulin-like growth factor 1-induced meiotic maturation develops during oogenesis, with cells 1.0 mm in diameter or larger responding in a size-dependent manner. Since insulin-induced oocyte maturation was shown previously to be p21 ras-dependent, experiments were performed to test whether a deficiency in the p21 ras system might account for meiotic incompetence in small oocytes (less than or equal to 0.9 mm diameter). Both small and large oocytes were found to contain comparable levels of membrane-associated p21, as determined by protein immunoblotting. Treatment of both small and large oocytes with 2 microM insulin for 2 hr increased endogenous levels of membrane-associated p21 by approximately 70%. Stimulation of microinjected p21-membrane association by insulin was observed to be both time- and concentration-dependent in large oocytes with an EC50 of 50 nM. In addition, comparable levels of GTPase activating protein were measured in extracts prepared from oocytes ranging from 0.8 to 1.3 mm in diameter. Therefore, the p21 system is apparently not limiting during oogenesis, and expression of some other cellular component must account for development of meiotic competence in Xenopus oocytes.

Animals↗
PubMed1992

H-1, C-13, and F-19 nuclear magnetic resonance assignments of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate.

The molecular structure of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate was analyzed by 1H, 13C, and 19F nuclear magnetic resonance (NMR) techniques; two-dimensional NMR was used to assigned 1H and 13C resonances. The 1H NMR spectrum in deuterated chloroform shows three sharp singlets (delta = 0.74, 0.79, and 2.00 ppm) integrating for three protons each, an isolated triplet at 4.55 ppm integrating for one proton, and overlapping multiplets between 0.72 and 2.12 ppm integrating for 31 protons. The 13C spectrum shows 18 resonances between 10 and 55 ppm, and three additional resonances at 82.9, 124.0, and 171.5 ppm. The 19F[1H] spectrum shows two sets of doublets (observed 2J = 150 Hz) at 5.00 and -4.80 ppm. Multiplets arising from 19F-13C J-coupling provide the starting assignment for all resonances by means of 1H homonuclear correlation (COSY) and 1H-13C heteronuclear correlation spectroscopy.

Androstanols↗
PubMed1992

Regulation of tissue noradrenaline in the rat myocardial infarction model of chronic heart failure.

OBJECTIVE: The aim was to evaluate mechanisms regulating tissue noradrenaline in congestive heart failure. METHODS: Tissue noradrenaline was measured in the conscious post myocardial infarction rat model of congestive heart failure and in sham operated rats (1) under control conditions, (2) 6 h after inhibition of tyrosine hydroxylase by the intraperitoneal administration of alpha-methyl-para-tyrosine (AMPT) (100 mg.kg-1 every 2 h), (3) 6 h after AMPT with desipramine pretreatment (0.3 mg.kg-1), and (4) following exhaustive exercise after AMPT. Tissue noradrenaline was extracted with perchloric acid and measured by high performance liquid chromatography with electrochemical detection. RESULTS: In control animals without drug, tissue noradrenaline concentration was lower in the following tissues in the rats with myocardial infarction compared with the sham operated group: left and right ventricles, spleen, soleus and white gastrocnemius muscles, kidney cortex, and tail artery. After AMPT, tissue noradrenaline concentration in the sham operated group was significantly lower than control; in the myocardial infarction group the fall in noradrenaline was only significant in the kidney, and group differences were no longer present. In the sham operated animals, coadministration of desipramine with AMPT attenuated the fall in tissue noradrenaline caused by AMPT in the heart and spleen. With exercise to exhaustion, cardiac noradrenaline was lower in rats with myocardial infarction than in sham operated rats, but higher in the soleus muscle. CONCLUSIONS: These data suggest that tissue noradrenaline depletion in congestive heart failure is not isolated to the heart, and it occurs despite activation of mechanisms that might be operating to conserve neuronal noradrenaline. One mechanism may be reduced organ blood flow to retard diffusion of noradrenaline into the circulation. If this increases interstitial noradrenaline concentration, it would facilitate prejunctional alpha 2 receptor restraint on noradrenaline release. Metabolic coronary vasodilatation during exercise reverses this process, and makes the heart most susceptible to noradrenaline depletion in congestive heart failure.

Animals↗
PubMed1992

Phase II trial of indicine N-oxide in relapsed acute leukemia of childhood. A report from the Childrens Cancer Study Group.

We treated 31 children with acute lymphoblastic leukemia (ALL), 14 children with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 child with chronic myelogenous leukemia (CML) in blast crisis (CALLA negative) with indicine N-oxide in a Phase II study. The efficacy and toxicity of the drug were assessed at two dose levels: 2,000 mg/m2/day for 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecutive days (17 patients). One patient with ALL at each dose level achieved a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. None of the patients with ANLL achieved a CR. Hepatotoxicity was mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patients (9%) experienced severe hepatotoxicity. Although indicine N-oxide has some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these two doses than at greater than or equal to 3,000 mg/m2/days for 5 consecutive days. Unfortunately, when the higher doses are administered to children, they are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity.

Acute Disease↗
PubMed1992

Antibodies are produced to the variable regions of the external envelope glycoprotein of human immunodeficiency virus type 1 in chimpanzees infected with the virus and baboons immunized with a candidate recombinant vaccine.

Chimpanzees infected with human immunodeficiency virus type 1 produce antibodies against the variable regions of the external envelope glycoprotein gp120. All five variable regions contain an epitope which is recognized by at least one of five chimpanzee sera. Each of the sera recognized a different pattern of epitopes. It is suggested that this varying response contributes to the emergence of variant viruses in the host. In contrast with the variability of the chimpanzees' response to replicating virus, that of baboons to a candidate recombinant vaccine is more uniform. Baboons injected with recombinant gp120 produced high levels of antibodies to epitopes within both the variable and conserved regions which coincided with epitopes previously shown to induce neutralizing antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Predictors of two-year post-hospitalization mortality among elderly veterans in a study evaluating a geriatric consultation team.

OBJECTIVE: To determine predictors of 2-year post-hospitalization mortality in a cohort of elderly hospitalized patients originally assembled to assess the impact of a Geriatric Consultation Team (GCT). DESIGN: Two-year follow-up of an inception cohort. SETTING: University-affiliated tertiary care VA Medical Center. PATIENTS: One hundred sixty-seven veterans age 75 or older discharged following hospitalization on medical, surgical, or psychiatry services but not intensive care units. INTERVENTION: None specifically studied here though cohort was previously part of randomized control trial of a Geriatric Consultation Team. MEASUREMENT: Mortality during 2 years of post-hospitalization follow-up. RESULTS: Two-year post-hospitalization mortality was 28 percent with no difference between the original GCT and control groups. For the entire sample, age, mental status, admission or discharge ADLs (but not change in ADL status), number of admission problems, number of discharge diagnoses, and discharge site were significant predictors of mortality in univariate analysis. Only discharge ADLs and discharge site remained significant in multivariate analysis. CONCLUSION: Measures of ADLs during hospitalization are stronger predictors of mortality following hospitalization than disease diagnoses. Impaired ADLs and placement other than at home are significant predictors of mortality, suggesting that the decision for nursing home placement contains other independently predictive information within it and/or that the subsequent nursing home period produces excess mortality. As had been indicated in short-term follow-up, there was no survival advantage for the Geriatric Consultation Group.

Activities of Daily Living↗
PubMed1992

Comparison of norepinephrine and isoproterenol clearance in congestive heart failure.

Congestive heart failure (CHF) is accompanied by increased sympathetic nervous activity. Previous studies have demonstrated that plasma norepinephrine (NE), a marker of sympathetic nervous activity, is elevated in CHF due to increased NE spillover into the circulation and decreased NE clearance. In this study we compared the clearance of NE and isoproterenol (ISO) in eight CHF subjects (plasma NE 601 +/- 133 pg/ml), and in nine controls (plasma NE 285 +/- 53 pg/ml) by using steady-state infusions of tritiated NE ([3H]NE) and tritiated ISO ([3H]ISO). Because ISO is not a substrate of neuronal reuptake but is removed from the circulation in a way that is similar to NE after neuronal reuptake blockade with desipramine, ISO clearance may permit a gross estimation of non-neuronal uptake of circulating NE. The NE clearance was lower in CHF than in the control group (CHF 1.25 +/- 0.13, controls 2.04 +/- 0.22 l.min-1.m-2; P = 0.009). The ISO clearance was reduced similarly in CHF (CHF 0.90 +/- 0.09, controls 1.59 +/- 0.12 l.min-1.m-2; P less than 0.001). Because the ratio of ISO to NE clearance was similar in both groups, our findings suggest that a low cardiac output in CHF decreases the availability of circulating catecholamines to tissue elimination sites.

Aged↗
PubMed1992

Effect of short-term fasting/refeeding on epidermal growth factor content in the gastrointestinal tract of suckling rats.

Epidermal growth factor (EGF) is trophic for varying regions of the developing gastrointestinal tract (GIT) of suckling rats. The presence of large amounts of EGF in milk from various species, combined with low production of EGF by suckling animals, led to speculation that milk is a major source of EGF for suckling rats. We report that short-term fasting (8 hr) of 12-day-old suckling rats resulted in a significant decrease in the levels of immunoreactive EGF (irEGF) in the GIT. Pups refed by lactating mothers for 1 to 4 hr exhibited an increase in irEGF to original levels, whereas pups fed a rat milk substitute by gastric gavage did not have an increase in irEGF content. The irEGF levels in the GIT of pups that were manually fed normal rat milk, or rat milk substitute supplemented with EGF, returned to the prefasted levels. Fasted suckling rats refed 2 ml of rat milk in 2 h exhibited significantly higher level of irEGF in the GIT than did those refed with 0.5 ml in 45 min. Since rat milk irEGF exists in three distinct forms (A, B, and C; C is equal to authentic submandibular gland EGF, the irEGF forms in the GIT were characterized by native polyacrylamide gel electrophoresis. In the stomach luminal contents of the fed suckling rats, only the larger form, Peak B, was observed. Both the luminal content and the mucosa scrapings of all other segments of all groups contained only Form D (comigrating with desarginyl EGF), a metabolic derivative of EGF. All forms were immunoreactive, exhibited receptor binding, and stimulated DNA synthesis in growth-arrested fibroblasts. The rapid changes in EGF within the GIT of suckling rats suggest the EGF can acutely modify some GIT functions of suckling rats.

Animals↗