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Biomedical subjects

J Peters

Publications and source records attributed to J Peters.

At least 271 records · Page 15Linked to original sources
PubMed1996

Genetic counseling in a Navajo hereditary nonpolyposis colorectal cancer kindred.

BACKGROUND: Cross-cultural genetic counseling was provided to an extended Navajo Indian family in which the MLH1 gene mutation for hereditary nonpolyposis colorectal cancer (HNPCC) had been identified. The family had been observed by the authors since 1983 and over the years had been provided with intensive education regarding the natural history of HNPCC as well as recommendations for cancer surveillance and management that was responsive to this natural history. METHODS: Following identification of the MLH1 mutation, DNA from family members was evaluated by a reference laboratory (OncorMed, Gaithersburg, MD), where sequences were checked in both the forward and reverse directions against the published sequence for MLH1. The 4bp deletion beginning at the first nucleotide of codon 727 was easily visualized in the heterozygous condition in both affected and predispositional individuals. The family was reeducated as a group and then provided further education individually during genetic counseling sessions, at which time they were appraised of potential penalties, such as insurance and employer discrimination, and psychological sequelae that could result from knowledge of the MLH1 mutation. Strict confidentiality of this information was assured. RESULTS: DNA testing was performed on 51 family members. Twenty-three individuals were counseled, seven of whom were positive for MHL1. Reactions ranged from full acceptance of the genetic implications to traditional Navajo reasoning such as the family had been cursed. CONCLUSIONS: DNA-based genetic counseling requires comparison and empathy, coupled with intensive preeducation regarding potential penalties and advantages that might emanate from this knowledge. Special care must be given to patients' culture, beliefs, and traditions.

Adult↗
PubMed1996

Detection of human viruses using primary cells immortalised by oncogene transfection, in comparison with primary cells and established cell lines.

No single established cell line was found capable of substituting for primary baboon kidney (PBK) or primary rhesus macacque kidney (PRK) cells for detection of human viruses. Although a panel of cell lines could detect influenza, parainfluenza, and enteroviruses, which are among the most important viruses encountered in routine diagnostic laboratories, the sensitivity of this panel was not as high as that of PBK or PRK cells. However, in a promising complementary approach, PBK and PRK cells have been immortalised successfully by oncogene transfection, and some of the resulting cell lines have retained susceptibility to human viruses, and may be suitable for routine diagnostic use.

Animals↗
PubMed1996

Population pharmacokinetics of intravenous amiodarone in patients with refractory ventricular tachycardia/fibrillation.

A population approach was used to determine the pharmacokinetics of amiodarone in 245 patients receiving intravenous amiodarone for the short-term treatment of refractory, hemodynamically destabilizing, ventricular tachycardia and/or fibrillation. A two-compartment model employing proportional statistical models to estimate intersubject variability and an additive-proportional model to estimate residual error were found to best describe the data. The mean (% coefficient of variation, CV) value for clearance was 0.22 L/hr/kg (13%), central volume of distribution was 0.30 L/kg (11%), peripheral volume of distribution was 10.0 L/kg (9.5%), and intercompartmental clearance was 0.71 L/hr/kg (16%). The mean (%CV) intersubject variance estimates were 1.52 (31%) for clearance, 0.37 (46%) for central volume, 0.37 (67%) for peripheral volume, and 0.44 (39%) for intercompartmental clearance. The estimate of residual error (%CV) was 0.53 (13%). Age, gender, height, serum creatinine concentration, serum alkaline phosphatase activity, ejection fraction, and therapeutic response to treatment did not contribute to the variability in patient pharmacokinetics. It was concluded that the pharmacokinetic parameters of amiodarone in these patients were similar to those reported for healthy volunteers and were similarly variable. Estimates of pharmacokinetic parameters made during short periods of observation may not be entirely consistent with parameters estimated during prolonged periods of observation of healthy volunteers who receive single doses.

Aged↗
PubMed1996

Circumvention of natural killer cell and T-cell mediated allogeneic target killing with tacrolimus (FK506) in small bowel transplantation related graft-vs-host disease.

The role of simultaneous donor-specific transfusion of unprocessed cellular bone marrow (BM) together with solid organ transplantation, a postulated concept to achieve long-term graft acceptance, was investigated in an experimental setting of semiallogeneic transplantation of parental small bowel (SBTx) to F1 hybrids. The established graft-vs-host (GvH) model revealed that simultaneous transfer of SB/BM substantially enhanced GvH-mediated immune responses in recipient target organs, e.g. skin, gut, and liver. In comparison to isolated SBTx, animal survival decreased from 16.1 (+/- 0.9) to 10.1 (+/- 0.8) days after additional BM transfusion, P < 0.001. Severe tissue injury of GvH-susceptible target organs in the setting of simultaneous SB and BMTx was associated with significant changes in recruitment and tissue distribution of NKR-P1+ cells during the GvH-related proliferative immune response. Tacrolimus effectively suppressed these initial events and prevented recipient animals from clinically and histologically observed damage caused by GvH disease.

Animals↗
PubMed1996

Swelling, intracellular acidosis, and damage of glial cells.

Cerebral ischemia and severe head injury among others are associated with a limited availability of oxygen, leading to cell catabolism as well as anaerobic glycolysis. Resulting metabolites, such as arachidonic- and lactic acid, can be expected to leak into perifocal brain areas, contributing there to cytotoxic swelling and damage of neurons and glia. Since elucidation of mechanisms underlying cell swelling and damage in the brain is difficult in vivo, respective investigations were carried out in vitro using suspended glial cells. Thereby, effects of arachidonic acid (AA) and of lactacidosis on glial cell volume, intracellular pH (pHi), and cell damage were analyzed utilizing flow cytometry. AA led to an immediate, dose dependent swelling and intracellular acidosis of glial cells. A concentration of 0.1 mM increased cell volume to 110% of control and decreased pHi to 7.05. Whereas glial swelling was permanent, pHi recovered to baseline after 90 min. Cell viability of 90% remained unchanged after addition of AA up to 0.1 mM, while at 0.5 mM it was significantly decreasing. Glial swelling from AA was nearly completely inhibited by the aminosteroid U-74389F or by using a Na(+)-free suspension medium for the experiment. Acidification of the medium to pH 6.8 or 6.2 led to a cell volume of 110% or 120% of control without affecting cell viability. The cells were not capable to defend their normal pHi during lactacidosis of the suspension medium but became acidotic as well. Addition of amiloride or utilization of Na(+)-free medium inhibited cell swelling from lactacidosis, while intracellular acidosis was even more pronounced. The results indicate that AA as well as acidosis are potent mediators of glial swelling and damage at levels found under pathophysiological conditions in the brain in vivo. Whereas intracellular acidification caused by AA was reversible, glial cells were unable to regulate their pHi during maintenance of extracellular acidosis. Concerning the mechanisms of glial swelling by AA, the production of oxygen- and lipid radicals might play a major role in the swelling process. The results indicate a role of the Na+/H(+)-antiporter in acidosis-induced glial swelling, whereas the exchanger has a limited significance for maintenance of pHi. As seen, the final pathway of glial swelling from both, AA and lactacidosis, requires a net influx of Na(+)-ions, probably together with Cl-ions, and osmotically obliged water.

Acid-Base Equilibrium↗
PubMed1996

Laparoscopic fundoplication 1 month prior to lung transplantation.

Upper midline laparotomy in the presence of pulmonary failure is often complicated by a prolonged period of mechanical ventilation postoperatively. We report the successful performance of laparoscopic fundoplication, without ventilatory support, in a woman with end stage pulmonary disease and resting hypercarbia, one month prior to lung transplantation.

Female↗
PubMed1996

Correlation between graft-versus-host induced immunosuppression and host natural killer cell activity in small bowel transplantation.

The occurrence of graft-versus-host disease (GvHD) following small bowel transplantation (SBTx) can be tuned by the recipient's initial natural killer (NK) cell activity, which modifies the immunogeneic balance between donor and host immunocompetent cells. This study was aimed to investigate the role of host NK cells on the incidence and severity of GvHD following SBTx. Intraperitoneal administration of 50 microl ascites fluid of the highly specific anti-NKR-P1 monoclonal antibody (mAb) 3.2.3 into F1 recipient animals on three consecutive days prior to SBTx was performed to suppress NK activity in F1 hybrids. In vivo treatment with 3.2.3 mAb effectively depleted recipient NK activity for at least 10 days in spleens and mesenteric lymph nodes of F1 hosts. In contrast to nontreated F1 recipients, all 3.2.3 mAb-pretreated F1 animals suffered from severe signs of GvHD, and the mean survival time was decreased significantly from 16.0 +/- 0.9 days to 11.0 +/- 0.8 days (p < 0.01) in nontreated and NKR-P1-depleted F1 animals, respectively. Other sequelae included earlier onset of GvH manifestations, pronounced damage of primary and secondary lymphatic organs, substantial increase in spleen index, and lower CD4(+)/CD8(+ )ratios over the course of progressing GvHD. Our results underline the important immunoregulatory role of NK cells as a first defensive line acting on the alloreactivity of donor-derived immunocompetent cells in this model of solid organ transplantation.

Animals↗
PubMed1996

Using buried water molecules to explore the energy landscape of proteins.

Buried water molecules constitute a highly conserved, integral part of nearly all known protein structures. Such water molecules exchange with external solvent as a result of protein conformational fluctuations. We report here the results of water (17)O and (2)H magnetic relaxation dispersion measurements on wild-type and mutant bovine pancreatic trypsin inhibitor in aqueous solution at 4-80 degrees C. These data lead to the first determination of the exchange rate of a water molecule buried in a protein. The strong temperature dependence of this rate is ascribed to large-scale conformational fluctuations in an energy landscape with a statistical ruggedness of approximately 10 kJ mol(-1).

Aprotinin↗
PubMed1996

Effects of an ambient air pollution intervention and environmental tobacco smoke on children's respiratory health in Hong Kong.

BACKGROUND: Two-thirds of complaints received by the Hong Kong Environmental Protection Department in 1988 were related to poor air quality. In July 1990 legislation was implemented to reduce fuel sulphur levels. The objective of this study was to measure the impact of the intervention on respiratory health in primary school children. METHODS: In all, 3521 children, mean age 9.51 years (SD = 0.78), from two districts with good and poor air quality respectively before intervention were followed yearly from 1989 to 1991. Children and parents reported the children's respiratory symptoms using self-completed questionnaires. Factor analysis was used to derive independent scores from 12 symptoms. Four groups of related symptoms were identified and binary variables (presence of any symptom in each group) were treated as dependent variables in modelling using generalized estimating equations procedures. RESULTS: In 1989 and 1990 an excess of respiratory symptoms was observed in the polluted compared with unpolluted district. The significant effects (odds ratio [OR], 95% confidence interval [CI], P value) associated with living in the polluted district were: cough and sore throat (OR = 1.22, 95% CI: 1.04-1.43, P < 0.01) and wheezing (OR = 1.35, 95% CI: 1.10-1.66, P < 0.01). After the intervention, in the polluted district only, sulphur dioxide levels fell by up to 80% and sulphate concentrations in respirable particulates by 38%. Between 1989 and 1990-1991 there was a greater decline in the polluted compared with the unpolluted district for reported symptoms of cough or sore throat, phlegm, and wheezing. The risks to respiratory health for children exposed to tobacco smoke in the home were higher than those for air pollution in both 1989 and 1990 and remained unchanged in 1991. CONCLUSIONS: Air quality can be improved by fuel controls but an effective intersectoral approach is required if other risks from environmental tobacco smoke are to be avoided.

Air Pollution↗
PubMed1996

Deletion of the long arm of chromosome 6: two new patients and literature review.

Two children with a partial monosomy 6q are reported: a girl with an interstitial deletion [46,XX,del(6)(q16.2q23.1)], and a boy with a terminal deletion [46,XY,del(6)(q25.1)]. Both children presented with developmental delay, facial dysmorphism and a cardiac defect. The patients have been studied using G banding and cosmid probes specific for the long arm of chromosome 6. Clinical data are compared with patients reported in the literature.

Abnormalities, Multiple↗
PubMed1996

The use of countercurrent heat exchangers diminishes accidental hypothermia during abdominal aortic aneurysm surgery.

BACKGROUND: Perioperative hypothermia is common and likely contributes to morbidity, but the efficacy of prophylactic fluid warning has hardly been analyzed systematically. We tested the hypothesis that the use of an infusion/blood warmer, based on the principle of countercurrent heat exchange, reduces incidence and degree of severe hypothermia following aortic surgery. METHODS: In a prospective randomized investigation of patients (n = 50) undergoing elective abdominal aortic aneurysm surgery, all fluids/blood products (approx. 3500 ml) administered intraoperatively were infused either (n = 25) via countercurrent-like heat exchangers (Hotline Level 1 Technologies Inc.) or without (n = 25) taking special precautions (infusions stored at 21 degrees C, blood products heated to 37 degrees C in a water bath). Anaesthesia was standardized using a thiopentone, fentanyl, vecuronium induction sequence, and maintained by isoflurane in N2O/O2. RESULTS: The perioperative decrease of oesophageal temperature (-0.35 degree C +/- 0.4) in the group managed with heat exchangers was significantly smaller (P < 0.0001) than in the control group (-1.5 degrees C +/- 0.54), and oesophageal temperature at the end of surgery was considerably higher (35.1 degrees C +/- 0.45 vs. 34.2 degrees C +/- 0.7; P < 0.0001). Furthermore, while postoperative hypothermia below 34.5 degrees C was observed in 16 patients (incidence: 64%) of the control group, it occurred in only 2 patients (incidence: 8%) managed with heat exchangers (P < 0.001). CONCLUSIONS: The efficacy of fluid/blood warmers has hitherto only been evaluated in bench tests. Our results demonstrate that the use of heat exchangers alone, while not completely preventing hypothermia, markedly reduces the incidence of severe perioperative hypothermia, and lessens its degree during abdominal aortic aneurysm surgery.

Aged↗
PubMed1996

Systemic availability of itraconazole in lung transplantation.

Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum.

Absorption↗
PubMed1996

Presence of renin within intramitochondrial dense bodies of the rat adrenal cortex.

It has been suggested that tissue-specific expression of the genes of the renin-angiotensin system (RAS) leads to local generation of angiotensin (ANG) II with specific physiological implications. We demonstrate here that an intracellular RAS exists in adrenal glomerulosa cells; 60 h after bilateral nephrectomy and hemodialysis, renin and prorenin were eliminated from the circulation, whereas intra-adrenal renin content increased (control rats: 2 +/- 0.5 ng ANG I.mg-1.h-1; anephric rats: 25 +/- 2). Thus renin is produced locally within adrenal cells. We obtained immunocytochemical and biochemical evidence for the presence of renin within intramitochondrial dense bodies of the zona glomerulosa. After nephrectomy, dense bodies increased in number, size, and renin content (control rats: 2.5 +/- 0.7 ngANGI.mg-1.h-1; anephric rats: 43 +/- 7). Angiotensin-converting enzyme (ACE) was also present within mitochondria and their dense bodies. In addition, in adrenal cortex of anephric rats, giant dense bodies were observed, which contain renin and strongly react with an anti-angiotensinogen antibody. The localization of renin, ACE, and angiotensinogen at these sites provides new evidence for the existence of an intracellular adrenal RAS.

Adrenal Cortex↗
PubMed1996

Targeted inactivation of the Ren-2 gene in mice.

Several recent studies have demonstrated that ablation of genes of the renin-angiotensin system can have wide-ranging and sometimes unexpected effects. Renin is directly involved in blood pressure regulation and is encoded by a single gene in most mammals. Wild mouse strains and some inbred laboratory strains have a duplicated renin gene (Ren-2), the physiological significance of which is unclear. Significant differences exist in the structure and expression of these renin genes, but as yet, no distinct biological function that distinguishes these genes has been defined. We have used gene targeting to discover the effects of inactivating the duplicated (Ren-2) gene in strain 129 mice, and we show that mice lacking the Ren-2 gene are viable and healthy. There appear to be no histopathological differences in renin-expressing tissues between Ren-2-null mice and their controls. Studies of our Ren-2-null mice allow, for the first time, a direct evaluation of the ability of the Ren-1d gene to regulate blood pressure in the absence of expression of the Ren-2 enzyme. We observed no alteration to blood pressure in adult mice homozygous for the mutated Ren-2 gene, even though the concentration of active renin is increased and of prorenin is decreased in plasma of these mice. Ren-1d is therefore capable of regulating normal blood pressure and despite a different tissue expression profile, is functionally equivalent to Ren-1c.

Animals↗
PubMed1996

Effects of gonadotropin-releasing hormone on bioactivity of follicle-stimulating hormone (FSH) and microstructure of FSH, luteinizing hormone and sex hormone-binding globulin in a testosterone-based contraceptive trial: evaluation of responders and non-responders.

Only a proportion of normal men participating in testosterone-based contraceptive trials develop azoospermia (responders). This study analyzed whether serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) are qualitatively different between responders and non-responders. Determination of in vitro bioactive FSH after stimulation with gonadotropin-releasing hormone (GnRH) and analysis of molecular heterogeneity of serum FSH, LH and SHBG was carried out by chromatofocusing and concanavalin-A affinity chromatography in eight men who had participated in a previous contraceptive study with testosterone buciclate. Blood was withdrawn at 15-min intervals on two basal occasions and 30, 45 and 60 min after i.v. administration of GnRH (100 micrograms). Pools of sera were separated by chromatofocusing in the pH range 3-6 and by lectin chromatography on concanavalin A. Immunoreactive FSH, LH and SHBG were assayed in the eluates. Bioactive FSH was analyzed by the rat Sertoli cell bioassay. Serum bioactive FSH increased after GnRH stimulation, without significant differences between responders and non-responders. The chromatofocusing profiles of serum FSH showed a significant shift towards the less acidic region after GnRH. The isoform distribution was similar in responders and non-responders. No significant differences were found in the relative proportion of FSH, LH and SHBG retained by concanavalin A. It is concluded that the extent of suppression of sperm production by androgen administration cannot be foreseen either on the basis of the response of bioactive FSH to GnRH administration or from the glycosylation pattern of serum FSH, LH and SHBG.

Adult↗