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Biomedical subjects

S Lynch

Publications and source records attributed to S Lynch.

At least 55 records · Page 3Linked to original sources

Detection of circulating donor deoxyribonucleic acid by microsatellite analysis in a liver transplant recipient.

The diagnosis of graft-versus-host disease following liver transplantation may be delayed because the clinical and pathological features are nonspecific. We report the use of microsatellites to support a diagnosis of GVHD in a patient who developed fever and a skin rash 28 days after liver transplantation. The pattern of microsatellite alleles amplified from the peripheral blood on day 51 posttransplant indicated that recipient and donor DNA were present in approximately equal proportions. Microsatellite typing is a simple and rapid method to identify high levels of circulating donor DNA to support a diagnosis of GVHD following liver transplantation.

Alleles↗

The management of difficult abdominal closure after pediatric liver transplantation.

Between January 1985 and December 1994, 164 liver transplantations were performed on 141 children. There were 100 reduced-size and 64 whole-liver grafts. Primary closure of the abdominal wound was not possible in 21 patients because of liver size, bowel edema, and distension. Temporary SILASTIC patch closure of the abdominal wound was used. For 16 of the 21 patients, removal of the SILASTIC patch and abdominal wall closure were completed by the seventh postoperative day; for the others, these were accomplished by the end of 2 weeks. The method is recommended when primary wound closure is not possible.

Child↗

Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects.

Localised folate deficiency has been implicated in colonic carcinogenesis and supplementation has been proposed for certain populations at risk. However, identifying those groups that may benefit is difficult as the relation between blood folate and gut epithelial cell values is unknown. The aim of this study was to define this relation. Epithelial cells mean (SEM) (sigmoid: 5.35 (0.56) x 10(6) cells, caecum: 6.6 (0.71) x 10(6) cells, duodenum: 4.0 (0.62) x 10(6) cells) were isolated from four endoscopic mucosal biopsy specimens (n = 25) by incubation with dithiothreitol (three hours) and EDTA (one hour). Lamina propria contamination was < 1%, with < 6% intraepithelial lymphocytes. Folate assay of isolates showed sigmoid colon folate content to be 20.1 (1.8) pg/micrograms DNA (10.2-46.6). In the same subject, caecal folate concentrations were lower (p < 0.01, n = 11) than sigmoid values, whereas duodenal isolates mirrored those of the sigmoid (19.4 (2.9) v 20.5 (3.2), n = 5). Sigmoid folate values were consistent over one to three weeks (n = 3). In a single case with blood folate deficiency, colonic values were normal. Serum folate and red cell folate correlated poorly with sigmoid epithelial cell folate content (r = 0.41, p = 0.063 and r = 0.17, p > 0.05 respectively). This study reports a modified ion-chelation isolation method for colonic biopsy specimens that yields large numbers of viable epithelial cells. Cell folate values remain constant with time though vary with intestinal region. The inability of serum or red cell folate values to predict those of the sigmoid epithelium suggests that they cannot identify those patients that might benefit from folate supplements.

Adolescent↗

RAG1 and RAG2 expression in human intestinal epithelium: evidence of extrathymic T cell differentiation.

We examined the hypothesis that the adult human gastrointestinal tract is a site of extrathymic T cell differentiation. When T lymphocytes undergo gene rearrangement, the products of both RAG1 and RAG2 genes are expressed; RAG mRNA is present only in tissue governing lymphocyte maturation. In this study, reverse transcription polymerase chain reaction (RT-PCR) was used to detect RAG1-and RAG2-specific mRNA. Total RNA was purified from small intestinal samples from five adults. Peripheral blood mRNA from the same patient was used as a negative control in two cases. Bone marrow RNA preparations from two healthy donors were used as positive controls. cDNA synthesis was carried out using random hexamers. Primers for first round and nested PCR of RAG1 and RAG2 were synthesized. RAG1 and RAG2 mRNA was detected in all bone marrow preparations but was absent in all peripheral blood samples. RAG1 and RAG2 mRNA was detected in the small intestine of four of the five patients studied. RAG1 and RAG2 expression was localized in the epithelial layer and absent in the lamina propria. RAG1 and RAG2 expression in the epithelial layer is strong evidence that T cell differentiation occurs in the adult human intestine.

Adolescent↗

Use of the donor iliac vein to replace the retrohepatic vena cava in pediatric reduced-size liver retransplantation.

The authors describe a new technique that used the donor common iliac vein and its bifurcation into the external iliac and internal iliac veins to replace the retrohepatic vena cava; this was used in a recipient who underwent her second reduced-size transplantation (segments II and III). Anastomosis of the donor hepatic vein to the internal iliac vein, with use of this segment of the venous graft to replace the retrohepatic vena cava, is for patients who have had more than one surgical procedure before liver transplantation.

Anastomosis, Surgical↗

Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults.

OBJECTIVES: The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH in a large number of hypopituitary adults. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH daily dose was 0.04 (0.02-0.05) IU/kg s.c. PATIENTS: Forty GH deficient hypopituitary patients (19 M, 21 F; aged 19-67 years) on conventional replacement therapy were studied. MEASUREMENTS: Serum insulin like growth factor I (IGF-I), skinfold thickness, total body potassium, total body water (TBW), exercise tolerance and muscle strength, and well-being. RESULTS: During the 6-month double blind phase, two GH treated patients withdrew because of adverse events. Lean body mass (LBM) increased and percentage body fat (%BF) decreased on GH but not on placebo (P) (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.9 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW increased on GH (P < 0.01) but not on P. No change was observed in waist-to-hip ratio or in muscle strength. During longer-term follow-up combining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Patients dropped out because of adverse events or lack of perceived benefit. Skinfold thicknesses decreased significantly at 6 and 12 months and the waist circumference at 6 months. Waist-to-hip ratio decreased significantly on GH at 12 months. LBM increased on GH treatment from 49.6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10.1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6,12 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 months of GH treatment. Muscle strength in selected muscle groups increased significantly at 6, 12 or 18 months of GH treatment. Randomization resulted in the placebo group having a greater GHQ score (higher morbidity) than the GH group before therapy. Over the controlled phase, GHQ scores improved on placebo but not on GH and CPRS score was unchanged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS: Growth hormone replacement therapy in adults for 6 months increased lean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintains the advantageous effects seen in shorter-term studies and may have additional effects on body fat distribution, muscle strength and psychological well-being.

Adult↗

Dietary flavonoids in atherosclerosis prevention.

More in vivo studies are needed to determine conclusively whether flavonoids inhibit the growth of atherosclerotic plaques, thus reducing the risk of atherosclerosis. In vitro data are contradictory, as the doses used may not be representative of the typical dietary intake of flavonoids, and not enough in vivo data exist to make conclusive statements. Exactly which flavonoid(s) may cause therapeutic benefit remains unclear because quercetin does not appear to be systemically absorbed, and myricetin and gossypetin have the potential to increase uptake of LDL by macrophages. More pharmacokinetic studies are needed to determine the bioavailability of each major dietary flavonoid. In vitro studies have shown that flavonoids possess potent antioxidant activity, which may slow oxidative modification of LDLs. Additional studies similar to the Zutphen Elderly Study and controlled clinical studies are needed, with more accurate estimates of daily flavonoid intake to determine conclusively whether a high-flavonoid diet reduces the rate of atherosclerosis. Until those studies are completed, consuming flavonoids cannot be recommended as a means to reduce the risk of atherosclerosis. Instead, one should focus on limiting the amount of saturated fats in the diet, smoking cessation, and participating in physical exercise to reduce risk of atherosclerosis.

Arteriosclerosis↗

Dopamine supersensitivity and hormonal status in puerperal psychosis.

BACKGROUND: We examine the dopamine receptor supersensitivity hypothesis of puerperal psychosis, and explore puerperal changes in the functional sensitivity of this receptor system. METHOD: Dopamine receptor sensitivity was estimated using growth hormone (GH) response to apomorphine challenge following delivery in 37 control women, and 11 deliveries in 10 women at 'high risk' of puerperal psychosis (previous history of puerperal affective or non-puerperal manic psychosis). Tests were on days 4 or 5, 11 or 12 and at six weeks postpartum. RESULTS: Three women developing puerperal psychosis had subsensitive GH responsiveness on day 4. GH response to 67 challenge tests (in control and 'high risk' women) increased between days 4 or 5 and six weeks postpartum (P < 0.05). GH response at six weeks correlated with free thyroxine levels (P < 0.01). CONCLUSIONS: These three cases do not support the stated hypothesis. Hypothalamic dopamine receptor sensitivity increases during the puerperium; thyroxine might influence this.

Adult↗

Adhesion molecules utilized in binding of intraepithelial lymphocytes to human enterocytes.

The expression of adhesion molecules by human duodenal intraepithelial lymphocytes (IEL) was examined by two-color flow cytometry. Resting IEL expressed LFA-1, HML-1, CD44. Stimulation with phytohemagglutinin (PHA) resulted in down-regulation of expression of these molecules with induction of expression of ICAM-1 and VLA-4. VLA-4 expression was also found on non-activated IEL from patients with celiac disease. In addition, IEL expressed an antigen recognized by a novel monoclonal antibody D2.1. The molecular mass of D2.1 is heterogeneous: 82 kDa in peripheral blood lymphocytes and 44 kDa in an IEL line. Expression of this antigen was also up-regulated by PHA. To determine the involvement of these antigens in binding of IEL to human enterocytes, we developed a system based on adherence of an IEL cell line to the I407 fetal intestinal cell line. Monoclonal antibodies VLA-4, D2.1 and to a lesser extent ICAM-1 blocked adherence of IEL to I407 cells. These data suggest that VLA-4 and D2.1 may be involved in adherence of IEL to human enterocytes or secreted matrix molecules in vivo.

Antibodies, Monoclonal↗

Psychiatric morbidity in adults with hypopituitarism.

Forty-one adults with established hypopituitarism and deficiency of growth hormone (GHD) were compared to an age and sex-matched group with another chronic metabolic disorder (diabetes mellitus) using standardized psychiatric rating and diagnostic measures. Nineteen (46%) of the GHD group were identified as definite psychiatric cases compared with 10 (24%) of the diabetics (odds ratio 1:9:1). The most frequent DSM III-R axis I psychiatric diagnoses were major depression (32% GHD patients and 10% of diabetic patients) and dysthymia. The risk of being a psychiatric case showed an association with duration of illness in the diabetic group, but not in the GHD group. Biochemical indices were not related to the risk of being a case in either group. Hypopituitarism is associated with a higher prevalence of psychiatric disturbance than can be attributed solely to the presence of a chronic disorder.

Adult↗

Lipoxin A4 metabolism by differentiated HL-60 cells and human monocytes: conversion to novel 15-oxo and dihydro products.

Lipoxins are tetraene-containing eicosanoids that possess biological activity in several organ systems. To determine their route of further metabolism, [11,12-3H]lipoxin A4 was prepared and incubated with human neutrophils, promyelocytic leukemia (HL-60) cells, and adherent monocytes. Intact neutrophils and undifferentiated HL-60 cells did not significantly metabolize [11,12-3H]LXA4, while HL-60 cells differentiated with PMA to monocyte/macrophage lineage rapidly (< 15 s) transformed this eicosanoid. The major radiolabeled LXA4-derived metabolites were characterized by physical methods and were shown to be 15-oxo-LXA4, 13,14-dihydro-15-oxo-LXA4, and 13,14-dihydro-LXA4. Substrate competition with cell-free supernatants from differentiated HL-60 cells suggests that lipoxins compete for 15-hydroxyprostaglandin dehydrogenase activity or an equivalent enzyme system. In addition, adherent monocytes exposed to [11,12-3H]LXA4 rapidly metabolized (> 60% within 30 s) the label to its oxo and dihydro derivatives. These results indicate that, unlike leukotrienes, LXA4 is subject to dehydrogenation and reduction of its conjugated tetraene to form triene-containing products. Moreover, they suggest that monocytes participate in lipoxin metabolism in their local milieu.

Alprostadil↗