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Biomedical subjects

D Andrews

Publications and source records attributed to D Andrews.

At least 19 recordsLinked to original sources

Oxidation of hemoglobin F is associated with the aging process of neonatal red blood cells.

Previously, we reported that in cord blood there is a population of very dense, surface area-depleted red blood cells (RBC). We hypothesized that oxidative damage might account for the generation of this cell population because Hb F is known to be mildly unstable in vitro. Accordingly, we examined density-separated subpopulations of neonatal red cells searching for evidence of oxidant injury to Hb in vivo. Cord or adult RBC were separated into populations of varying density and an increased amount of membrane-associated globin was found in the densest fraction of cord RBC. Solubilized ghosts from each fraction were analyzed by thiol-disulfide exchange chromatography for the presence of oxidized Hb and spectrophotometrically for the presence of membrane-bound hemichrome. About four times more oxidized Hb was found in unseparated cord RBC than in adult RBC. This difference was most evident in the densest 10-15% RBC subfractions. Membrane-bound hemichrome levels in cord cells were twice those found in adult cells. We found that in cord membrane skeletons there was 2.5 to 9 times as much globin in the dense fraction as compared to the light fraction. Membrane skeletons from dense and light adult RBC differed little from one another. We postulate that membrane (and perhaps membrane skeleton)-associated oxidized Hb is a marker for more generalized oxidative damage, which may create the population of unusually dense cells found in cord blood and ultimately shorten their life span.

Adult

Laparoscopic cholecystectomy in an infant.

Use of the laparoscopic approach in traditionally open procedures has developed rapidly in recent years. Despite this intensive rate of evolution, most procedures have been done in adult patients, with pediatric patients largely excluded. This paper reviews a case report of a laparoscopic cholecystectomy in a 19-month-old male. This effort presents new data and techniques to encourage further investigation into minimally invasive surgery in the pediatric age group.

Cholecystectomy, Laparoscopic

Subepiglottic cyst causing upper airway obstruction in a neonatal calf.

A 14-day-old female Brahman calf was referred because of respiratory stridor since birth. Radiography and endoscopy were used to diagnose a pharyngeal cyst, which was subsequently surgically removed. The subepiglottic location and histopathologic features of the cyst were consistent with origin from an embryologic thyroglossal duct remnant.

Airway Obstruction

Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats.

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.

Administration, Oral

Rifampin and ansamycin interactions with cyclosporine after renal transplantation.

Cyclosporine whole blood concentrations are routinely monitored to help ensure optimal therapy. Several drugs have been shown to alter cyclosporine disposition by altering hepatic metabolism. Rifampin, a potent enzyme inducer, has been demonstrated to increase cyclosporine clearance. The effects of ansamycin, a chemically related investigational antibiotic, on cyclosporine disposition, have not been previously published. We report a renal transplant patient receiving cyclosporine and consecutive therapy with rifampin and ansamycin. When compared to rifampin, ansamycin's effect on cyclosporine disposition appeared to be delayed and of less magnitude. Further characterization of this interaction is required. Until this issue is resolved, we would advise careful monitoring of cyclosporine blood levels in patients receiving either rifampin or ansamycin in concert with cyclosporine.

Anti-Bacterial Agents

Effects of chest physical therapy on lung function in children recovering from acute severe asthma.

The effects of chest physical therapy in acute severe asthma in children have been studied in 38 children aged 6 to 13 years in a randomized placebo controlled trial. The study began between 6 and 24 hours after admission to hospital; 19 children received chest physical therapy (PT) and 19 children received placebo visits. Each child had 4 treatments over 2 days which were preceded by nebulized salbutamol. Lung volumes and flow rates were measured in a body plethysmograph before salbutamol and before and after either PT or placebo on the first and fourth treatments. Throughout the study standard asthma drug therapy was given. In both groups characteristics such as sex, race, age, height, weight, severity, and baseline lung function were similar. Taking into account the baseline, lung function at the end of the study was similar in both groups. Three 12 year old children in the PT group showed improvements in flows above those seen in any children in the placebo group. We conclude that chest PT, when combined with asthma drug therapy, does not improve lung function in most children in this age group with acute severe asthma.

Adolescent

Isolation and partial characterization of a glial hyaluronate-binding protein.

A glial hyaluronate-binding protein (GHAP) with an isoelectric point of 4.3-4.4 was isolated from human brain white matter. The 60-kDa glycoprotein appeared to be quite resistant to proteolysis, and comparison with GHAP from a viable glioma removed at surgery showed that the protein isolated from autopsy material was not a degradation product resulting from postmortem autolysis. The protein was localized immunohistochemically with mouse monoclonal and rabbit polyclonal antibodies in cerebral white matter. Only small amounts could be found in the gray matter. After enzymatic deglycosylation, an immunoreactive 47-kDa polypeptide was obtained. Two amino acid sequences of GHAP showed a striking similarity (up to 89%) with a highly conserved region of cartilage proteins (bovine nasal cartilage proteoglycan and rat and chicken link protein). However, the amino acid composition and other amino acid sequences suggested that there are also differences between brain-specific GHAP and cartilage proteins.

Amino Acid Sequence

Structural similarity of hyaluronate binding proteins in brain and cartilage.

A glial hyaluronate-binding protein (GHAP) was isolated from human brain white matter by affinity chromatography on immobilized hyaluronate. The 60 kDa protein appeared remarkably homogeneous by reversed-phase high pressure liquid chromatography analysis. Four cyanogen bromide peptides and 10 tryptic peptides were characterized by amino acid sequence, a total of 12 sequences since overlaps were found between 2 cyanogen bromide and 2 tryptic peptide sequences. Two sequences of brain GHAP had similarity with rat link protein, a hyaluronate binding protein in cartilage. The region of similarity was contained in the evolutionary conserved COOH-terminal half of link protein which is involved in the binding of hyaluronate. The remaining 10 amino acid sequences of brain GHAP had no similarity with link protein, nor with previously reported protein sequences. The findings suggest that the hyaluronate binding domains of such diverse proteins as brain GHAP and cartilage link protein are similar, probably due to the fact that hyaluronic acid is highly conserved in evolution.

Amino Acid Sequence

Examining protein translocation in cell-free systems and microinjected Xenopus oocytes.

A variety of assays have been developed which permit rapid and unambiguous determination of the membrane topology adopted by newly synthesized proteins. Cell-free systems and microinjected Xenopus oocytes are two of the most attractive approaches for characterizing the elements in both the nascent polypeptide and the membrane which together determine the final orientation of the protein in the membrane. Careful analysis of the mechanism of protein translocation using these methods has revealed a number of unusual topologies. The applications of a number of different assays for endoplasmic reticulum membrane translocation are described for the most commonly used cell-free systems (wheat germ and reticulocyte lysate), as well as for microinjected Xenopus oocytes.

Animals

Predictors of burnout in professional and paraprofessional nurses working in hospitals and nursing homes.

Burnout is a phenomenon in which the cumulative effects of a stressful work environment gradually overwhelm the defenses of staff members, forcing them to psychologically withdraw. To understand the experience of professional and paraprofessional nurses suffering from burnout requires a close examination of the environments in which they function. This study examined interpersonal, intrapersonal and situational factors expected to contribute to the six dimensions of burnout among nursing staff who worked in acute care and long-term care health facilities. The sample included 312 professional and paraprofessional nurses. The following research question was explored using a series of stepwise multiple regression analyses: of the following variables interpersonal (professional exposure to patients with poor prognosis for survival, work relationships, informal support), intrapersonal (coping strategies, fear of death, comfort working with patients with poor prognosis for survival) and situational (personal and work demographics), which are the significant predictors of the six dimensions of burnout in professional and paraprofessional nurses? Findings revealed that work relationships and tension-releasing and instrumental problem-focused coping were the most powerful predictors of burnout. Based upon this, it was concluded that nursing burnout is both an organizational and a personal problem. Recommendations for practice are presented.

Acute Disease

Using microcounseling to teach RN nursing students skills of therapeutic communication.

This study assessed the degree to which nursing students acquired and retained six generic skills of communication. Fifty-three second year female RN students were randomly assigned to either an experimental group (E-group) which received microtraining, or a nonattention control group (C-group). All subjects completed both the Carkhuff Indices of Communication and Discrimination as pretests. The E-group then had approximately 25 hours of microtraining in six basic communication skills. Following training, each subject completed the Carkhuff Indices again, the Empathy Construct Rating Scale, and a 10- to 15-minute audiotaped interview in which she assumed the role of a helping nurse. Multivariate analysis of covariance indicated a significant main effect suggesting that the E-group performed better than the C-group when all the measures were combined together. As well, the experimental trainees performed significantly better than the control trainees on empathy, reflection of feeling, and summarizing. The E-group made fewer communication errors, asked fewer closed-questions, made more Good responses, and showed a significant increase in empathy over training. At the nine-month follow-up, while there were no statistically significant differences between the groups on any dependent measure, the E-group outperformed the C-group on all dependent measures.

Adolescent

Amino acid sequence of toxin F, a snake venom toxin that blocks neuronal nicotinic receptors.

The amino acid sequence was determined for toxin F, a component of Bungarus multicinctus venom that blocks nicotinic transmission in the chick ciliary ganglion and the rat superior cervical ganglion. Toxin F was purified by a procedure that includes preparative isoelectric focusing and ion exchange chromatography. Seventy nanomolar toxin F blocks nicotinic transmission in the chick ciliary ganglion; however, the toxin only weakly blocks the binding of 125I-alpha-bungarotoxin to membranes derived from Torpedo californica electroplax (IC50 = 1 microM). These data raise the possibility that toxin F may preferentially recognize neuronal nicotinic receptors. Toxin F focused identically on an isoelectric focusing gel with samples of two similar toxins, bungarotoxin 3.1 and kappa-bungarotoxin. The sequence of toxin F is identical with that recently reported for kappa-bungarotoxin. When the N-terminal portion of bungarotoxin 3.1 was sequenced, it was found to be identical to the other two toxins. These and other data suggest that the 3 toxins are, in fact, the same.

Amino Acid Sequence

Tryptophanyl adenylate formation by tryptophanyl-tRNA synthetase from Escherichia coli.

By gel filtration and titration on DEAE-cellulose filters we show that Escherichia coli tryptophanyl-tRNA synthetase forms tryptophanyl adenylate as an initial reaction product when the enzyme is mixed with ATP-Mg and tryptophan. This reaction precedes the synthesis of the tryptophanyl-ATP ester known to be formed by this enzyme. The stoichiometry of tryptophanyl adenylate synthesis is 2 mol per mole of dimeric enzyme. When this reaction is studied either by the stopped-flow method, by the fluorescence changes of the enzyme, or by radioactive ATP depletion, three successive chemical processes are identified. The first two processes correspond to the synthesis of the two adenylates, at very different rates. The rate constants of tryptophanyl adenylate synthesis are respectively 146 +/- 17 s-1 and 3.3 +/- 0.9 s-1. The third process is the synthesis of tryptophanyl-ATP, the rate constant of which is 0.025 s-1. The Michaelis constants for ATP and for tryptophan in the activation reaction are respectively 179 +/- 35 microM and 23.9 +/- 7.9 microM, for the fast site, and 116 +/- 45 microM and 3.7 +/- 2.2 microM, for the slow site. No synergy between ATP and tryptophan can be evidenced. The data are interpreted as showing positive cooperativity between the subunits associated with conformational changes evidenced by fluorometric methods. The pyrophosphorolysis of tryptophanyl adenylate presents a Michaelian behavior for both sites, and the rate constant of the reverse reaction is 360 +/- 10 s-1 with a binding constant of 196 +/- 12 microM for inorganic pyrophosphate (PPi).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate

Factors that determine the long-term results of percutaneous transluminal dilatation for peripheral arterial occlusive disease.

Seven hundred thirty-one percutaneous transluminal dilatations (TLDs) for peripheral arterial occlusive disease were performed between 1978 and 1984. From this prospective study 666 dilatations were analyzed with a combination of clinical and objective vascular laboratory tests to determine which factors could be used to predict long-term successful results. Eleven variables were recorded at the time of TLD. The proportional hazards model (Cox regression) identified four significant variables predictive of long-term success: the indication for the procedure (claudication or salvage), site of the dilatation (aortoiliac or femoropopliteal), runoff (poor or good), and whether a previous TLD was done at the same site. With these significant variables, the Cox model was used to estimate the chances of success at 1, 2, and 3 years for all combinations of variables. The accuracy of the Cox model was confirmed by the close approximation between the number of observed and predicted successful TLDs at 1, 2, and 3 years. We concluded that the chances of success of TLD in terms of percentage at 1, 2, and 3 years can be predicted from the combinations of these four significant variables. Knowledge of these factors should permit better selection of patients for this procedure.

Aged

The relationship between affective disorder and eating disorders: a review of the literature.

The authors review the relationship between affective disorder and anorexia nervosa and bulimia across five lines of inquiry: clinical reports, psychometrics, family history, drug studies, and follow-up investigations. They conclude that affective disorder and eating disorders are related but that the nature of the relationship is unclear. After discussing possible mediating patterns, the authors propose an interactive, multidetermined understanding as the most appropriate model. They recommend that future research in this area attempt to identify subpopulations of patients with affective disorder and eating disorders by means of a longitudinal, multilevel strategy with serial determinations.

Adolescent