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Biomedical subjects

D Holt

Publications and source records attributed to D Holt.

At least 55 records · Page 3Linked to original sources
PubMed1996

Plasma immunoreactive endothelin concentration correlates with severity of coronary artery disease in patients with stable angina pectoris and normal ventricular function.

OBJECTIVES: The present study tested the hypothesis that plasma immunoreactive endothelin concentration correlates with the severity and extent of coronary atherosclerosis. BACKGROUND: Plasma endothelin-1 concentration is increased in patients with unstable coronary syndromes and advanced atherosclerosis. This finding, together with other clinicopathologic observations, suggests that endothelins may participate in the atherogenic process. However, the relation between plasma immunoreactive endothelin and coronary artery disease in patients with stable angina pectoris remains controversial. METHODS: Ninety consecutive patients undergoing coronary angiography for the investigation of exertional chest pain and 49 normal control subjects were prospectively studied. Eleven patients had normal coronary angiographic findings (group I), 65 had coronary artery stenoses (group II), and 14 had coronary artery disease plus symptoms indicating atheroma in other vascular territories (group III). Computerized angiography was used to determine the extent, severity and morphology of coronary stenoses. Plasma immunoreactive endothelin was measured by radioimmunoassay. RESULTS: Mean (+/- SD) plasma endothelin concentration (pg/ml) was significantly higher in patients than in control subjects (7.29 +/- 4.07 vs. 3.48 +/- 1.29, p < 0.0001). Endothelin levels were higher in patients of group III than in those of groups II and I (9.43 +/- 5.48, 7.20 +/- 3.72 and 4.94 +/- 2.89, respectively, p = 0.02). In patients of group II, plasma endothelin correlated with the maximal degree of stenosis in each patient (r = 0.25, p = 0.04) and with the number of stenoses with > or = 70% diameter narrowing (r = 0.36, p = 0.002). The highest plasma endothelin levels were found in patients with total occlusions (8.65 +/- 3.78 vs. 6.46 +/- 3.51 p = 0.02). CONCLUSIONS: Plasma immunoreactive endothelin concentration is increased in patients with chronic stable angina. The higher levels occur in patients with severe stenoses and total coronary occlusion.

Adult↗
PubMed1996

Immunohistochemical manifestations of unilateral kidney ischemia.

Events in the early post-transplant period have been correlated with increased renal allograft loss. Immunologic reactions and ischemic injury have been implicated in this process. While the immunologic aspects of allograft injury have been studied extensively, ischemic effects remain less well understood. To study the effects of ischemia in rats with different genetic backgrounds without the introduction of an alloimmune response, a clamp was placed on the vascular pedicle of the left kidney for 60 min. The short-term effects (1 wk) of ischemia were studied in groups of PVG (RT1c), LEW (RT1), DA (RT1a) and WR (RT1u) rats, Immunoperoxidase staining demonstrated limited infiltration of monocytes, macrophages, and T-cells accompanied by upregulation of low levels of MHC class II antigens on tubular epithelial cells, peritubular capillaries, and interstitial cells in kidneys of PVG and WF rats. Kidneys of LEW and DA rats had greater influxes of monocytes, macrophages, and T cells in addition to higher amounts of MHC class II antigens upregulation on tubular epithelium and interstitial cells. The long-term effects of ischemia were studied in kidneys of WF rats. These kidneys had a progressive increase in infiltrating T cells, monocytes, macrophages and MHC class II expression on the tubular epithelium and the interstitial cells at 14, 30, and 90 d after the ischemic insult. The differences in MHC class II expression between ischemic kidneys of PVG and LEW rats were not associated with differences in production of mRNA for IL-2, IFN-gamma, and TNF-alpha. In summary, transient renal ischemia in the absence of an allogeneic immune response triggers a progression of inflammatory responses, including leukocyte infiltration, cytokine production and MHC class II antigen upregulation which appears to be strain-dependent.

Animals↗
PubMed1995

Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumopericardium associated with positive-pressure ventilation in a cat.

Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumopericardium with hypotension and tachycardia were observed after endotracheal intubation and during positive-pressure ventilation in a previously healthy cat anesthetized for ovariohysterectomy. Potential causes included tracheal tearing during intubation, a closed pop-off valve while using high oxygen flows, and preexisting acquired or congenital abnormalities in the respiratory tract. The cat responded well to conservative management, including cessation of positive-pressure ventilation and use of increased inspired oxygen concentration.

Animals↗
PubMed1995

Acute generalized exanthematous pustulosis.

A case of acute generalized exanthematous pustulosis (AGEP) is described. A brief review of AGEP is undertaken with emphasis on its differentiation from acute generalized pustular psoriasis. AGEP is also compared with and contrasted to acute febrile neutrophilic dermatosis, or 'Sweet's syndrome' and Sneddon-Wilkinson pustular dermatosis.

Adrenal Cortex Hormones↗
PubMed1994

Diagnosis and management of laryngeal disease in the dog and cat.

The larynx of the dog and cat controls the air flow to the lungs and prevents food or fluid from entering the airway during swallowing. Also, the larynx is important for vocalization and generating the explosive force necessary to expel material from the airways during the cough reflex. This article discusses the diagnosis and management of laryngeal disease in the dog and cat.

Animals↗
PubMed1994

Case report: toxic shock syndrome arising from cellulitis.

Toxic shock syndrome is a febrile, multiorgan illness related to toxins elaborated by staphylococcal or streptococcal infections. In the 1980s, most cases were associated with menstruation. More recently, many cases now are unrelated to menses. In this article, the authors describe a case of a nonmenstruating woman with toxic shock syndrome, associated with cellulitis of her arm. Cultures of the arm grew Staphylococcal aureus, which produced enterotoxin B.

Adult↗
PubMed1993

Chloramphenicol toxicity.

Although high serum concentrations of chloramphenicol are related to toxicity, as shown experimentally and during treatment, the mechanism of toxicity remains unclear. Published work suggests that relatively minor metabolites may be causally related to toxic reactions in vitro and some of these metabolites have been detected in sera from treated patients. It is possible that all the major toxic manifestations of chloramphenicol may be explained by attack by free radicals. Depletion in compounds acting as cellular antioxidants, such as glutathione and vitamin E, may conceivably increase the vulnerability of an individual to chloramphenicol toxicity, while supplementation with an antioxidant might protect against it. Research into the metabolism of chloramphenicol and into the mechanism of its toxicity has declined since early work in the 1950s and 1960s, but its continuing use worldwide means that there is justification for renewed interest in the toxicology of this useful antibiotic.

Animals↗
PubMed1992

Correlation between thoracic radiographs and postmortem findings in dogs with hemangiosarcoma: 77 cases (1984-1989).

Thoracic radiographic and postmortem findings were compared in dogs with histologically confirmed hemangiosarcoma (HSA). On the basis of results of radiography, a false-negative diagnosis was made for pulmonary HSA in 10 (21.7%) of 46 dogs, and in 26 (53.1%) of 49 dogs for cardiac HSA. The incidence of false-negative radiographic diagnosis for pulmonary HSA was lower in dogs when left and right lateral views were obtained. The radiographic sensitivity was 78%, and the negative-predictive value was 74% for pulmonary HSA. The radiographic sensitivity was 47%, and the negative-predictive value was 43% for cardiac HSA.

Animals↗
PubMed1990

Stability of plasma amiodarone levels during chronic oral therapy.

The variability of plasma amiodarone levels in 51 patients receiving chronic oral therapy over 4-53 (median 19) months was examined; 3-14 (median 5) plasma samples were obtained. After a loading dose, most patients received either 200 mg or 400 mg a day. Mean plasma amiodarone concentration was 1.2 +/- 0.6 mg/l and mean plasma desethylamiodarone concentration was 1.2 +/- 0.5 mg/l. No relationship was seen between height and weight and plasma concentrations. Dose was a significant predictor of plasma level (p less than 0.01) although it was a poor predictor of steady state amiodarone concentration.

Administration, Oral↗
PubMed1990

Consensus document: Hawk's Cay meeting on therapeutic drug monitoring of cyclosporine.

The optimal measurement method and clinical application of the therapeutic drug monitoring of cyclosporine remain uncertain. At a workshop held at Hawk's Cay, FL, from January 14 to January 17, 1990, 57 scientists presented their latest research findings, either in formal papers or as discussants. Lively debate and discussion followed presentation of extant and new methodologies for drug measurements as well as multicenter validation studies: applications of trough-concentration monitoring in renal, hepatic, and bone-marrow transplants as well as in autoimmune disease; and alternative pharmacokinetic approaches to guide cyclosporine therapy. The process of inducing and maintaining optimal immunosuppression to facilitate graft success is a complex and often challenging task, requiring the combined expertise of multiple disciplines. Thus, the assembly of four of the groups essential to the transplant process--clinicians, laboratory scientists, the pharmaceutical company, and the manufacturers of cyclosporine measurement kits--provided a unique opportunity to evaluate therapeutic drug monitoring issues facing the transplant field. Here we present the major conclusions reached at the meeting, brief discussions of the study data on which they are based, and a summary of unresolved problems that will require further rigorous investigations. The Consensus Document was reviewed by all the workshop participants before we submitted this final manuscript.

Chromatography, High Pressure Liquid↗
PubMed1988

The teratogenicity of cadmium-metallothionein in the rat.

A single dose in the range 0.25-1.0 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation (gd 8-gd 14), is teratogenic. In vitro, the development of the isolated rat conceptus, explanted at 8.5 days of gestation, is unaffected by the addition of 1.5 microM MT-Cd to the culture medium, whereas the same concentration of ionic Cd (as CdCl2) is lethal. The incorporation of appreciable amounts of Cd into the embryo (860 pg), placenta (970 pg) and yolk sac (65.4 ng) without toxic manifestations under the former conditions suggests that the metalloprotein is incorporated pinocytotically, but without degradation, by the conceptus in vitro. It does not follow, therefore, that MT-Cd is without embryo/foetotoxicity in the pregnant rat since, in-vivo, liberation of some of the protein-bound Cd is known to occur in the blood. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, however, the maximal foetal and placental contents of Cd (less than 25 pg and 2 ng, respectively) are low in comparison with those after a teratogenic dose of CdCl2 and are of the same order as those in the embryo (46 pg) and placenta (100 pg) + yolk sac (3.8 ng) of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl2 (0.065 microM). From this evidence, therefore, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and, because of this, result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia, since they are induced in pregnant, normal rats by appropriate reductions in food intake. In rats that are injected i.p. on gd 12 with 0.25 mg MT-Cd/kg body weight, renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Teratogenicity of ionic cadmium in the Wistar rat.

In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i.v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25-2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i.p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.

Animals↗
PubMed1987

Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--IV. Mechanisms of intestinal copper accumulation.

Copper-67, administered either parenterally or via the maternal milk, accumulates principally in the intestine and liver of the 6-day-old pup. Most of the 67Cu in the soluble fraction of the intestine is associated with the heterogeneous Cu-complex, which is located predominantly in the ileum. The rates of uptake and loss of 67Cu in the liver and intestine indicate that enterohepatic circulation of Cu in the neonate is appreciable. Whilst the concentration of Cu in the bile of the 13-day-old pup is high (16-fold greater than that in the adult male rat), translocation of Cu from both the liver and duodenum to the ileum probably occurs via the blood, rather than by the reabsorption of biliary Cu. Although the Cu-complex normally seems to be retained within the distal intestine until the enterocytes are desquamated, Cu in this form is utilized when the Cu-intake of the neonate is restricted.

Animals↗
PubMed1986

The toxicity and teratogenicity of mercuric mercury in the pregnant rat.

Mercuric mercury (Hg2+), when injected IV into the pregnant Wistar rat, is retained mainly in the maternal compartment and uptake by the conceptuses is small. Thus if the dose is based on total body weight, the maternal body burden, particularly in late gestation, is greater than the whole body burden in the non-pregnant animal. The LD50 of Hg2+ (mg/kg total body weight), however, remains essentially constant (1.0-1.2 mg Hg2+/kg) throughout pregnancy. It seems, therefore, that the rat becomes more resistant to Hg2+ with increasing gestational age. This increased resistance does not correlate with differences in (a) the uptake of Hg2+ by the kidneys, the target organs of toxicity, (b) the severity of the histopathologically detected renal damage and (c) the inhibition of glomerular filtration. Biochemical measurements, however, suggest that kidney function may become less susceptible to Hg2+ as pregnancy advances from conception to near term. During mid-gestation the minimum effective teratogenic dose of Hg2+ (0.79 mg/kg total body weight) is high in relation to the maternal LD50 and the incidence of foetal malformations, mainly brain defects (23% in all live foetuses), is low. In rats of different gestational ages uptake of Hg2+ by the embryo/foetus at this dose level decreases sharply between day 12 and day 13. The teratogenic effects in the foetus and both the structural and functional damage to the maternal kidneys, however, are essentially the same in animals that are dosed with Hg2+ either immediately before, or immediately after these gestational ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1986

Comparison of some biochemical effects of teratogenic doses of mercuric mercury and cadmium in the pregnant rat.

Mercuric mercury (Hg2+), like cadmium (Cd2+), interferes with the transport of certain essential metals to the conceptus in the pregnant Wistar rat and, at 48 h after the IV injection of a teratogenic dose (0.79 mg Hg2+/kg body weight) on day 12 of gestation, the foetal concentrations of Zn2+, Cu2+ and Fe3+, but not of Mg2+, are reduced significantly. Both Hg2+ and Cd2+, at teratogenic dose levels, inhibit the placental and foetal uptake of 65Zn2+ and 67Cu2+, but possibly by different mechanisms. In addition, the effects of Hg2+, at different times after dosing, on the uptake of these labelled tracers and of 59Fe3+, administered as 15-min pulses, do not parallel the changes in the placental and foetal concentrations and contents of the endogenous, stable metallic ions. The teratogenic dose of Hg2+ inhibits the placental and foetal uptake of L-[4,5-3H]-leucine, but not the incorporation of the labelled amino acid into foetal protein. In contrast, the corresponding dose of Cd2+ inhibits both leucine uptake and protein synthesis in the placenta and foetus. Similarly, Cd2+ inhibits the uptake of [2-14C]-thymidine and its incorporation into foetal DNA, whereas Hg2+ reduces the placental and foetal uptake, but has little or no effect on the utilization of the nucleoside. Since both Cd2+ and Hg2+ reduce the foetal uptake of 65Zn and the foetal concentration of Zn, but only Cd2+ interferes with DNA synthesis, it is unlikely that the inhibition of the metabolism of thymidine can be attributed to reduction in thymidine kinase activity in consequence of foetal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--III. Effects of closure.

The ileum of suckling rats contains a high level of copper, most of which is concentrated within cytoplasmic vesicles of the enterocytes. Intestinal closure, 20-21 days after birth, results in the replacement of enterocytes by cells devoid of these vesicles and there is a concomitant fall in the level of copper in the ileum. Administration of cortisone acetate (0.5 mg/g body wt) to 5-day-old rats results in premature loss of copper-laden ileal enterocytes and an 80-90% decrease in the ileal copper concentration. The loss of copper is mainly from the soluble fraction of the tissue and is proportionally greater from the high molecular weight-protein fraction rather than from the copper complex.

Animals↗