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Biomedical subjects

L Williams

Publications and source records attributed to L Williams.

At least 253 records · Page 14Linked to original sources

The presence and significance of intraepithelial mesenchymal cells in human foetal colon.

During an investigation of the morphogenesis of the human foetal colon, breaks in the basal lamina underlying the surface epithelium were frequently observed at 10 1/2-11 weeks. These occurred at those sites where the mesenchyme was sweeping up into the epithelium prior to the transformation of the epithelium from stratified to a single layer. At the same time numbers of mesenchymal cells appeared among the epithelial cells and some were observed actually in the process of passing through the gaps in the basal lamina. Close contact was apparent between some mesenchymal cells and basal epithelial cells through extended breaks in the basal lamina. Many of the mesenchymal cells within the epithelium contained numbers of apoptotic bodies. This suggests that one of the functions of the intra-epithelial mesenchymal cells is to remove the debris resulting from cell death which occurs in association with the re-arrangement of cells during development of the colon.

Basement Membrane↗

Aplastic anaemia incidence in parts of the United Kingdom in 1985.

This paper describes the distribution of new cases of aplastic anaemia in parts of the UK in 1985. The age, sex and spatial pattern are described. Special attention is given to the investigation of five childhood cases which occurred close in space and time. The results are contrasted with similar data from elsewhere.

Adolescent↗

Complications requiring operative intervention after orthotopic liver transplantation.

Survival rates after liver transplantation continue to improve, but the postoperative morbidity in these patients remains significant. The clinical courses of 96 consecutive patients who received transplants were reviewed retrospectively. Forty-two patients experienced complications requiring surgical intervention. These complications were primarily related to biliary tract reconstruction, bowel complications, and septic complications. None of the factors examined, except a second transplant procedure, proved helpful in identifying those patients most likely to experience surgical complications; however, a risk factor scoring system was found to accurately identify that group of patients at highest risk of dying in the postoperative period. Only 2 of 21 deaths could be attributed directly to the surgical complication. We believe that a policy of prompt, aggressive surgical intervention, coupled with careful tailoring of immunosuppression to both the patient and the clinical situation, can lead to a low mortality rate in patients who require reoperation.

Adult↗

Cardiotonic agents. Synthesis and inotropic activity of a series of isoquinolin-3-ol derivatives.

A series of isoquinolin-3-ol derivatives (II) was prepared as analogues of the clinical cardiotonic agent bemarinone (ORF 16600, I). Although in many respects the structural requirements for the cardiotonic activity of II are similar to those of bemarinone, certain differences between the series were noted. Our structure-activity studies show that II is less sensitive to alkoxy-substitution effects than is I, and more significantly, 4-substitution of II by alkyl groups, halogen, or alkanecarboxylic acid derivatives enhances cardiotonic activity in II in contrast to I, wherein analogous substitution eliminated activity. A linear correlation between contractile force (CF) increase and cyclic nucleotide phosphodiesterase fraction III (PDE-III) inhibition by the title compounds was determined. The isoquinoline derivatives were characteristically short-acting cardiotonic agents with good potency and selectivity.

Animals↗

Reduced lipid peroxidation in dilated hearts of cardiomyopathic turkeys.

Adverse pulmonary reactions to some nitrofuran antibiotics are thought, in part, to involve production of reactive oxygen radicals. Furazolidone, a nitrofuran antibiotic, causes a dilated cardiomyopathy in domestic turkeys. The mechanism of this drug induced cardiomyopathy is unknown. We investigated the possible role of free radical injury in this heart failure model. Left ventricular lipid peroxidation capacity, assessed by two methods (the thiobarbituric acid reactive substances and lipid hydroperoxides assays respectively), was investigated in five 5-8 week old cardiomyopathic turkeys with severe cardiac dilatation, left ventricular dysfunction and systemic hypotension, and in five control birds. Superoxide dismutase activity, total and manganese, was also measured in the crude left ventricular homogenates. Both lipid peroxidation products were reduced in the myopathic hearts: thiobarbituric acid reactive substances (malondialdehyde) 70(SEM 4) v 86(3) nmol.100 mg protein-1 in controls, p less than 0.02; and lipid hydroperoxides 29(7) v 74(14) nmol.100 mg protein-1, p less than 0.02. Total superoxide dismutase activity was similar in cardiomyopathic and control hearts: 670(26) v 657(105) nitrite units.100 mg protein-1. Although total superoxide dismutase activity was unchanged, we found decreased manganese superoxide dismutase in the dilated hearts compared with controls (54% v 84% of total activity, p less than 0.02). In separate in vitro experiments furazolidone (2-10 mg.g wet weight-1) did not increase malondialdehyde production in turkey (or rat) left ventricular homogenates. These results indicate that cardiomyopathy induced by furazolidone is associated with decreased myocardial lipid peroxidation. Although as yet unexplained, the decrease may be due to a diminished amount of heart lipid susceptible to peroxidation accompanying the process of cardiac hypertrophy and dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Provocation discography as a guide to planning operations on the spine.

In a prospective study we attempted to define the role of lumbar discography in the investigation of patients with low back pain with or without non-dermatomal pain in the lower limb. The records of 195 patients were studied at least two years after a technically successful operation. Of 137 patients in whom discography had revealed disc disease and provoked symptoms, 89% derived significant and sustained clinical benefit from operation. Of 25 patients whose discs showed morphological abnormality but had no provocation of symptoms on discography only 52% had clinical success. These findings support the continued use of lumbar discography for the investigation of this particular group of patients.

Adolescent↗

Efficacy and safety of two-year therapy with transdermal clonidine for essential hypertension.

We evaluated the safety and efficacy of transdermal clonidine (TC) in 23 patients with essential hypertension over a two-year period. Fourteen patients achieved control of blood pressure using TC alone. Six patients achieved control with a combination of TC and the diuretic chlorthalidone (CH). Three patients had control with CH alone or did not achieve control with either TC alone or TC plus CH and were dropped from the study. Of the 20 patients remaining in the study, six patients remained on TC or TC plus CH for the two-year study. Ten of the 20 patients quit the study because of skin reactions and four because of other side effects. No clinically significant changes were noted in serum or urinary laboratory parameters. Finally, TC was effective as long-term monotherapy for essential hypertension in only four of our patients. The major limitation is skin-related side effects.

Administration, Cutaneous↗

The relationship between physical and sexual abuse and illicit drug use: a replication among a new sample of youths entering a juvenile detention center.

The relationship between child physical and sexual abuse and illicit drug use are little understood and underinvestigated. Our previous study of this association found that a sample of detained youths' physical and sexual abuse experiences were related significantly and positively to their use of illicit drugs. Data gathered from a new sample of detained juveniles, interviewed 3 years after our first study, relating to this issue were examined and our previous findings were replicated.

Adolescent↗

Changes in life-style after liver transplantation.

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation.

Achievement↗

Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks.

Trimetrexate, a new antifolate compound, was administered by 30-min infusions weekly for 3 weeks to 29 patients with solid tumors in a Phase I study. Thrombocytopenia was dose limiting, but highly variable among patients at a given dose level; other toxicity was mild and uncommon. Twenty-three patients participated in pharmacokinetic studies and five patients participated in a study of the effects of trimetrexate on [6-3H]-deoxyuridine incorporation into hematopoietic cell DNA. The median total body clearance of trimetrexate for each dose level was independent of dose but the total body clearance varied widely among patients at a given dose level. The magnitude of the fall in platelet count in individual patients correlated well with the amount of exposure to trimetrexate, but not with the extent of prior therapy. The amount of [6-3H]deoxyuridine incorporation into hematopoietic cell DNA at 72 h after drug administration correlated with the total body clearance of trimetrexate. The total body clearance of trimetrexate was reduced in patients with impaired hepatic synthetic function, as judged by low pretreatment serum albumin concentrations. The recommended Phase II starting dose on this schedule is 130 mg/m2 weekly for 3 weeks; patients with hypoalbuminemia should be treated at lower doses.

Adenocarcinoma↗

Homogeneous enzyme immunoassay (EMIT) protocol for monitoring tricyclic antidepressants on the COBAS-BIO centrifugal analyzer.

EMIT tests are available for quantitative determination of the tricyclic antidepressants amitriptyline (AMI), nortriptyline (NORT), imipramine (IMI), and desipramine (DMI). An extraction step before analysis eliminates cross-reacting polar metabolites. Excellent correlation between EMIT and high-performance liquid chromatography (HPLC) has been previously established. Most published protocols for using EMIT reagents on COBAS-BIO centrifugal analyzers were designed for analytes present at 1-50 mg/L in serum. AMI, NORT, IMI, and DMI are usually present at far less than 1 mg/L. We describe a COBAS-BIO EMIT protocol for assaying these analytes. Patient sample correlation between COBAS-BIO EMIT and EMIT-AutoLab were greater than 0.99. Between-run precision for single-point determinations was comparable to SYVA AutoLab performance [less than or equal to 11% at 40 micrograms/L AMI, NORT, IMI (80 micrograms/L DMI), and less than or equal to 4% at 200 micrograms/L AMI, NORT, IMI (400 micrograms/L DMI)]. With stored-curve updating, working reagents were usable for at least 14 days (AMI) or 23 days (DMI).

Antidepressive Agents, Tricyclic↗

Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

Biliary Atresia↗