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Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 289 records · Page 16Linked to original sources
PubMed1994

Insulin sensitivity and glucose tolerance following transposition of pancreatic venous drainage to the systemic circulation.

In these studies it has been demonstrated that the diversion of pancreatic venous drainage to the systemic circulation (1) increases the peripheral insulinemia and metabolic clearance of glucose under basal conditions; (2) decreases insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp, more than 2-fold; and (3) decreases peripheral insulin sensitivity and the suppression of endogenous glucose production during exogenous glucose infusion. In spite of these changes, tolerance to the intravenously infused glucose improves. This is accounted for by higher insulin concentrations following diversion, more than compensating for decreases in insulin sensitivity and the suppression of endogenous glucose production. Data on insulin sensitivity and glucose tolerance after pancreas transplantation are not completely consistent, as discussed above. When the site of venous drainage of the pancreas was the only factor altered in the experimental model, unequivocal insulin resistance resulted. This occurred in a relatively short period (ie, 2 weeks). The results here are consistent with a number of studies that have demonstrated normal glucose tolerance coupled with hyperinsulinemia in a partially pancreatectomized dog model as well as in human pancreas transplants. Data presented here imply that the hyperinsulinemia which results after surgical diversion of the pancreatic venous drainage from the portal to the systemic circulation causes an important degree of insulin resistance. Physiological insulin delivery and therefore portal drainage during transplantation may therefore be relevant for the complete normalization of glucoregulation in diabetes. The reduction of hyperinsulinemia may also be important in light of the recent emphasis on the role that this and insulin resistance may play in the development of complications such as cardiovascular disease or hypertension.

Animals↗
PubMed1994

Response of the endothelium to trauma and sepsis. Adherence, cytokine effects and procoagulatory response.

Trauma and sepsis induced organ dysfunction is the result of an overwhelming inflammatory response, in which the endothelium plays a central role. Within the mediator cascade reactions involve thrombin, histamine induced endothelial "stimulation" and endotoxin/cytokine induced endothelial "activation" in the endothelial/leukocyte interactions. Adherence events beyond the physiological degree lead to endothelial damage, increase of permeability and result in organ dysfunction. Activated endothelial cells are further involved in cytokine production and they are important actors in the procoagulatory/anticoagulatory balance. The homeostasis is disturbed in the systemic inflammatory response, which leads to a procoagulant state of the endothelium and severe coagulation disorders.

Blood Coagulation↗
PubMed1994

Aortic valve replacement with pulmonary homografts. Early experience.

The increasing use of the aortic homograft as aortic valve substitute and the limited availability of donor valves prompted us to consider the pulmonary homograft as an alternative substitute for aortic valve replacement. The aim of our study is to compare the ultrastructural and biomechanical properties of pulmonary homograft leaflets with those of their aortic counterpart and to present the early results of using the pulmonary homograft for aortic valve replacement. Light and transmission electron microscopy have shown that pulmonary homograft leaflets are thinner than the aortic with a lesser content of elastic tissue in the ventricularis layer. However there were no substantial differences in the ultrastructure. Uniaxial tensile tests were done on 69 cusps from human pulmonary and aortic valves using an Instron testing machine. The strain at 200 KPa was found to be similar for both pulmonary and aortic leaflets (8.20% +/- 2.87% versus 8.98% +/- 1.90%) cut circumferentially. Radial strips appear to be more extensible in pulmonary leaflets than in aortic (32.6% +/- 7.5% and 28.6% +/- 11.1%, respectively). The ultimate tensile strength for circumferential strips was found to be similar for both aortic and pulmonary valves (1460 +/- 857 kPa versus 1450 +/- 689 kPa), but there was relatively little difference between the radial strips (295 +/- 95 kPa versus 252 +/- 104 kPa). A total of 123 patients whose ages ranged between 13 and 78 years received either fresh antibiotic sterilized or cryopreserved pulmonary homografts for aortic valve replacement. The pulmonary homograft was inserted in place of the patient's diseased aortic valve by using one of two different techniques: freehand in the subcoronary position or as a "short cylinder" inside the aortic root. There was three hospital deaths (2.43%; 70% confidence limits = 1.08% to 4.83%). Cumulative follow-up was 184 patient-years (range 1 to 39 months). All surviving patients have been followed up with serial color flow Doppler echocardiography. There were no late deaths. Actuarial late survival was 97.5% (70% confidence limits = 95.7% to 98.6%) at 3 years. Four patients (2.2%/pt-yr) underwent reoperation because of severe aortic regurgitation (1, 4, 12, and 15 months after the operation) because of technical problems (mismatch in size between the pulmonary homograft and aortic anulus) in three patients and probably because of graft rejection in one patient. At 3 years the actuarial rate of freedom from reoperation was 95.5% (70% confidence limits = 92.7% to 97.3%). Mild aortic regurgitation has been detected in three patients (2.6%). No patients incurred thromboembolic episodes or infective endocarditis.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1993

Natural cycloheximide resistance in yeast. The role of ribosomal protein L41.

The yeast Kluyveromyces lactis is resistant to high concentrations (1 mg/ml) of the antibiotic cycloheximide. Using in vitro translation studies it was confirmed that this extreme resistance is a property of ribosomes. The resistance determinant from K. lactis was cloned into Saccharomyces cerevisiae. Nucleotide sequence analysis of the determinant demonstrated that resistance was conferred by the K. lactis ribosomal protein L41. K. lactis was shown to contain only one copy of the gene that encodes this protein and the gene was located to chromosome III. In contrast, S. cerevisiae was found to contain multiple copies of the gene for the corresponding ribosomal protein L41 which mapped to two of the three chromosomes V, XIV and VIII. Since the cycloheximide-resistance gene of K. lactis causes essentially complete protection against inhibition by the drug, it is likely to be particularly useful as a selective marker in eukaryotic gene transfer studies.

Amino Acid Sequence↗
PubMed1993

Direct diagnosis of myotonic dystrophy with a disease-specific DNA marker.

BACKGROUND: Myotonic dystrophy is the most common inherited form of muscular dystrophy affecting adults. Its symptoms are not confined to muscle, and variability in their nature and in the patient's age at their onset can make diagnosis difficult. A specific unstable DNA sequence associated with myotonic dystrophy has recently been identified. We describe the use of a DNA probe (p5B1.4) that can detect this mutation directly, improving the accuracy and speed of diagnosis. METHODS: We analyzed DNA extracted from the peripheral-blood lymphocytes of 112 unrelated patients with myotonic dystrophy and their families, using molecular genetic techniques. Southern blot analysis and amplification with the polymerase chain reaction were used to determine the extent of expansion of the unstable DNA sequence. RESULTS: Probe p5B1.4 allowed direct identification of the myotonic dystrophy mutation in 108 of the 112 unrelated patients. In three families for whom the clinical and genetic data obtained with linked probes were ambiguous, the probe identified persons at risk for symptoms of this disorder and demonstrated that a possible sporadic case of myotonic dystrophy was familial. In one of these families the size of the unstable myotonic dystrophy-specific fragment decreased on transmission to offspring, who remained asymptomatic. CONCLUSIONS: The diagnosis of myotonic dystrophy is improved by the use of a probe that detects directly the mutation responsible for this disorder.

Adolescent↗
PubMed1993

"Infectious" transplantation tolerance.

The maintenance of transplantation tolerance induced in adult mice after short-term treatment with nonlytic monoclonal antibodies to CD4 and CD8 was investigated. CD4+ T cells from tolerant mice disabled naïve lymphocytes so that they too could not reject the graft. The naïve lymphocytes that had been so disabled also became tolerant and, in turn, developed the capacity to specifically disable other naïve lymphocytes. This process of "infectious" tolerance explains why no further immunosuppression was needed to maintain long-term transplantation tolerance.

Animals↗
PubMed1993

Isolation and ordering of bacteriophage genomic clones corresponding to two YACs from 19q13.3.

We describe a method for rapidly isolating overlapping bacteriophage clones corresponding to the genomic region cloned in a yeast artificial chromosome (YAC) that does not require sub-cloning or lambda DNA preparation. Purified YACs from 19q13.3 were used to screen a flow-sorted chromosome 19 library, and the resulting positive clones were characterized using inter-Alu PCR. In addition, aliquots of the lambda stocks were gridded out, and hybridized with probes known to be present in the YACs, thereby avoiding having to perform DNA preparations. The application of this technique in the identification of lambda clones which span the myotonic dystrophy (DM) locus on 19q13.3 is presented, and its general advantages are discussed.

Bacteriophage lambda↗
PubMed1993

How to build a kidney.

Embryonic kidney is ideal for the study of epithelial morphogenesis--rich in developmental processes, accessible and clinically important. Interactions between mesenchyme and the epithelium invading it cause the epithelium to differentiate and branch to form the collecting ducts, and the mesenchyme to epithelialise into excretory nephrons. Molecular analyses reveal complex programmes of expression of transcription factors and morphoregulatory molecules, correlating with induction and morphogenesis. In developing nephrons especially, the detailed timing of this programme is now being explored and the functions of some molecules involved have been tested by inhibition experiments. New pharmacological methods of induction may also prove useful in solution of the mechanisms by which a kidney is formed.

Epithelial Cells↗
PubMed1993

Interleukin-8 release in baboon septicemia is partially dependent on tumor necrosis factor.

The role of tumor necrosis factor (TNF) in interleukin (IL)-8 release in septicemia in the baboon (2-h infusion of live Escherichia coli, 5 x 10(8) cfu/kg) was investigated. Four experiments were done: one control (n = 7) and three with pretreatment to reduce TNF plasma levels. Pretreatment was with anti-TNF antibody (anti-TNF) 15 mg/kg, which neutralized circulating TNF (n = 4); 0.5 mg/kg of anti-TNF, which reduced peak TNF from 6.2 ng/mL (controls) to 0.6 ng/mL (n = 4); and a xanthine derivate (HWA138), which reduced TNF to 1 ng/mL (n = 5). With TNF levels < 1 ng/mL, a significant reduction of circulating IL-8 from 10.4 ng/mL (peak) in controls to 1 ng/mL (peak) in anti-TNF-treated animals was found, but with HWA138 only some decrease in IL-8 was seen. Despite high endotoxin levels (10-30 ng/mL peak), neutralization of TNF resulted in diminished release of IL-8 and significantly lower levels of granulocyte elastase.

Animals↗
PubMed1993

Human islet isolation--a prospective randomized comparison of pancreatic vascular perfusion with hyperosmolar citrate or University of Wisconsin solution.

University of Wisconsin solution has become the most commonly used vascular perfusate during multiorgan donation world-wide. In the UK however, hyperosmolar citrate remains in common use. The purpose of this prospective randomized study was to compare the effect of systemic perfusion with UW or HOC on subsequent islet yield and purification for pancreata with short cold ischemic times. Seven pancreata were randomized to each group, with the donor age, pancreas weight, and period of cold ischemia being similar in both. Perfusion with UW was shown to inhibit collagenase digestion, and a higher concentration of this enzyme was needed to achieve comparable numbers of islets with good separation of exocrine and islet tissue after a similar period of digestion. There were no differences in the number, size, purity, or viability of islets between the two groups. In conclusion, UW solution offers no benefits over HOC for pancreata with short cold ischemic times, and because of its expense and need to use greater amounts of collagenase enzyme, we continue to use HOC.

Adenosine↗
PubMed1993

Very early analysis of graft establishment after allogeneic bone marrow transplantation using the polymerase chain reaction.

We have used minisatellite polymorphisms flanking the apolipoprotein B locus and PCR to demonstrate the emergence of donor specific alleles in peripheral blood at 3-7 d post allogeneic bone marrow transplantation (BMT). This technique affords a very early indication of the establishment of stable engraftment, and may identify patients at risk of graft failure or leukaemic relapse. Patterns of T-cell chimaerism in the first 7-14 d following transplantation may be closely associated with the development of graft-versus-host disease (GVHD), the graft versus leukaemia (GVL) effect and graft rejection and future application of this technique to the investigation of early T-cell chimaerism may give further insights into these immunologically mediated events.

Alleles↗
PubMed1993

Teicoplanin in combination: role in the management of the febrile neutropenic patient.

The spectrum of microorganisms responsible for infection in neutropenic patients has changed in the last decade, with Gram-positive organisms now predominant. New antibiotic strategies have been required and have evolved to cope with this change. In particular, the optimal timing of glycopeptide antibiotic use has been addressed. Both teicoplanin and vancomycin are highly effective agents for susceptible Gram-positive organisms. Teicoplanin has advantages in terms of ease of administration and lower toxicity, while vancomycin has proved durable over many years' use. There are now firm indications for the use of glycopeptide antibiotics in febrile neutropenic patients, including clinically defined central venous catheter infection and microbiologically documented infection with susceptible organisms. The empirical use of the glycopeptide antibiotics in combination with other agents as first-line treatment, however, is less certain. The utility of this approach remains controversial and ultimately depends on the extent to which local practice favours the emergence of Gram-positive infections in neutropenic patients.

Adult↗
PubMed1993

Antibiotic preparations contain DNA: a source of drug resistance genes?

Fluorescence measurements and polymerase chain reaction amplification of streptomycete 16S ribosomal DNA sequences were used to show that a number of antibiotic preparations employed for human and animal use are contaminated with chromosomal DNA of the antibiotic-producing organism. The DNA contains identifiable antibiotic resistance gene sequences; the uptake of this DNA by bacteria and its functional incorporation into bacterial replicons would lead to the generation of antibiotic resistance determinants. We propose that the presence of DNA encoding drug resistance in antibiotic preparations has been a factor in the rapid development of multiple antibiotic resistance in bacteria.

Anti-Bacterial Agents↗
PubMed1993

Post mortem examinations of HIV infected patients: a nationwide survey.

AIMS: To identify the number and geographical distribution of post mortem examinations performed on HIV infected cadavers; to identify the areas that perform post mortem examinations so that, by invitation and discussion, a national post mortem network could be initiated. METHODS: A nationwide survey of Royal College of Pathologists' district tutors (n = 216) was done by postal questionnaire. These were completed by the district tutors or passed on to their histopathologist colleagues. The results were collated after three months. After one follow up letter, an 86% response rate, which is a significant sample, was achieved. RESULTS: Twenty eight per cent of respondents were performing HIV post mortem examinations. Of those who were not performing them (30%), the lack of clinical or coroner requests was the most common explanation. All regions provide facilities for HIV post mortem examinations, as judged by the responses. CONCLUSIONS: These findings are of singular importance as it is the first United Kingdom survey investigating the distribution of post mortem examinations on HIV infected cadavers. Studying post mortem material using a systemic, coordinated collection of brain tissue is essential to increase knowledge of a new disease of pandemic proportions.

Autopsy↗
PubMed1993

Altruism towards the end of life.

In the author's experience most normal healthy adults would like to have the choice of medical help to die if they become incurably ill and find their suffering intolerable. The reasons for this are explored, based on ten years of listening and talking about the subject to a wide variety of people in many countries. The most familiar and common are the avoidance of futile suffering and the desire to retain autonomy. This paper concentrates on the dislike of losing independence and its closely associated wish to continue to behave altruistically. Some reasons for the general lack of recognition of the last two are suggested.

Activities of Daily Living↗
PubMed1993

Tumor necrosis factor is a mediator of phospholipase release during bacteremia in baboons.

Phospholipase A (PLA) activity is elevated in plasma after polytrauma and in sepsis. During both situations, tumor necrosis factor (TNF) and free fatty acids (FFAs) are also increased. To determine whether there is a relationship between the changes in PLA and in TNF that occur during sepsis, we used a primate model of bacteremia. Live Escherichia coli (5 x 10(8) colony-forming units/kg) was injected into anesthetized baboons (n = 10). Four of these animals were pretreated with an anti-TNF antibody (anti-TNF Ab, 15 mg/kg). After the administration of bacteria (2 h), the plasma TNF was 10.2 +/- 3.2 ng/ml. PLA and FFA reached their maximum values of 191 +/- 14 U/l and 1.5 +/- 0.3 mM at 10 and 24 h after the injection of bacteria, respectively. In the animals treated with anti-TNF Ab, plasma TNF was undetectable; the highest values recorded for PLA and FFA were 71 +/- 23 U/l and 0.7 +/- 0.3 mM, respectively. Thus TNF appears to be an important mediator of PLA release during sepsis.

Animals↗
PubMed1993

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

To assess the metabolic consequences of the diversion of the pancreatic venous drainage to the systemic circulation, the pancreaticoduodenal and gastrosplenic veins were anastomosed to the inferior vena cava in nine normal dogs. This procedure maintained the integrity of the entire pancreas while shunting the hormonal output of the pancreas to the periphery. The metabolic effects were assessed from the sensitivity to insulin during a euglycemic hyperinsulinemic glucose clamp using an insulin infusion of 800 microU/kg per min. The studies were controlled by their duplication in seven dogs identically treated but with the pancreatic veins reanastomosed to the portal vein. No differences in systemic insulin levels or insulin sensitivity before and after surgery were seen under these circumstances. After diversion, however, basal insulin levels rose from 4.5 +/- 1.0 to 11.5 +/- 2.5 microU/ml. Basal glucose metabolic clearance rate (MCR) rose to 3.0 +/- 0.4 from 2.0 +/- 0.3 ml/kg per min. On insulin infusion, maximal stimulation of MCR within the 2-h infusion period was to 15.2 +/- 2.5 ml/kg per min preoperatively and to 7.2 +/- 0.8 ml/kg per min after diversion. Using ratios of MCR-to-insulin concentration as an index of insulin sensitivity, it was demonstrated that this index decreased by at least 50% after diversion. These data imply that portal venous drainage of the pancreas is an important factor in the determination of peripheral insulin sensitivity.

Anastomosis, Surgical↗