Search PubMed⌕ Search

Biomedical subjects

J Lynch

Publications and source records attributed to J Lynch.

At least 181 records · Page 10Linked to original sources
PubMed1993

Nuclear magnetic resonance study of cerebrospinal fluid from patients with multiple sclerosis.

Proton nuclear magnetic resonance (NMR) spectroscopy was used to examine cerebrospinal fluid (CSF) from patients (n = 30) with actively progressive multiple sclerosis (MS). Metabolite concentrations obtained from the spectra were compared to those determined from the spectra of CSF from control patients (n = 27) with benign spinal disorders. No significant difference was found between the 2 groups for most constituents, including lactate, glutamine, citrate, creatine and creatinine, and glucose. Acetate levels were significantly higher in MS patients, while formate levels were significantly lower, than the controls. There were no significant differences in metabolite concentrations in CSF from early and longstanding MS patients. A peak due to an unidentified compound was found at 2.82 ppm in the spectra of CSF from patients with actively progressive MS, but not in the spectra of CSF from the controls. The peak was not found in spectra of CSF from patients with AIDS dementia complex (n = 9) or Parkinson's disease (n = 5), but it did appear in spectra of CSF from 1 patient with Jakob-Creutzfeldt disease (out of 3 examined) and from 1 patient (out of 7) with Guillain-Barré disease. The unidentified compound is volatile and, from the chemical shift of the observed NMR peak, is probably an N-methyl compound. As such, it may be an intermediate in the cholinoglycine cycle, in which an abnormality has been proposed to exist in MS patients.

Adult↗
PubMed1993

Expression of endothelin receptor subtypes in rabbit saphenous vein.

Recent investigations have revealed the presence of vasoconstrictory endothelin (ET)-B receptors in several tissues, including the rabbit saphenous vein (RSV). To determine the nature of the ET binding sites in RSV, radioligand-receptor binding studies with selective ligands and Northern analyses with probes from the ET-A and ET-B receptor cDNAs were conducted. ET-1 inhibited 125I-ET-1 binding to RSV in a monophasic manner, with an inhibition constant (Ki) of 0.08 +/- 0.02 nM and a slope factor of 0.9 +/- 0.1. ET-3 inhibition of 125I-ET-1 binding was biphasic, with 68% of the 125I-ET-1 binding sites being displaceable with a Ki value of 31 +/- 4 nM. The remaining 32% of the sites displayed high affinity for ET-3 (Ki = 0.2 +/- 0.1 nM). The ET-A-selective peptide BQ-123 inhibited 125I-ET-1 binding in a biphasic manner, with Ki values of 10.4 +/- 1.9 nM and 3.2 +/- 0.9 microM. The high affinity BQ-123 site comprised 70% of the binding sites, whereas the low affinity site comprised 30%. The correspondence of high affinity binding sites for BQ-123 and low affinity binding sites for ET-3 is consistent with the suggestion that 70% of the 125I-ET-1 binding sites in this tissue are ET-A receptors. To further investigate the nature of the ET-B binding sites in RSV, 125I-ET-3 competition binding experiments were conducted. ET-1 and BQ-123 inhibited 125I-ET-3 binding in RSV with Ki values of 40 +/- 7 pM and 7.2 microM, respectively, whereas inhibition curves for ET-3 and the ET-B receptor-selective agonist sarafotoxin S6c (S6c) were best fit to two-site models. Resultant Ki values for ET-3 and S6c were 50 pM (71%)/4 pM (29%) and 0.7 nM (71%)/95 nM (29%), respectively. Binding in RSV differed from that in rat cerebellum, where ET-3 and S6c inhibition of 125I-ET-3 binding was monophasic (Ki values of 70 pM and 1.1 nM for ET-3 and S6c, respectively). The presence of the nonhydrolyzable guanine nucleotide analog guanosine-5'-O-(3-thio)triphosphate (200 microM) did not affect 125I-ET-3 binding. Low stringency Northern analysis of RSV RNA with [alpha-32P]dCTP-labeled fragments from the ET-A or ET-B receptor cDNAs revealed similar hybridization patterns with both probes, with two resolved RNA species migrating at 4.7 and 1.8 kilobases.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

A breast-ovarian cancer susceptibility gene maps to chromosome 17q21.

Nineteen North American Caucasian families that contain a minimum of four confirmed cases of breast or ovarian cancer have been studied. Four polymorphisms (cLB17.1, D17S579, D17S588, and D17S74), which span a region of approximately 15 cM on chromosome 17q12, were typed. Our data confirm the location of a dominant gene conferring susceptibility to breast and ovarian cancer (maximum lod = 9.78) and suggest that the breast-ovarian cancer syndrome is genetically heterogeneous. Two recombinants in one large family suggest that the breast-ovarian cancer locus lies between D17S588 and D17S579.

Adult↗
PubMed1992

Hereditary flat adenoma syndrome: a variant of familial adenomatous polyposis?

We describe the clinical and pathologic features in four extended kindreds that are consistent with the hereditary flat adenoma syndrome (HFAS). This colon cancer susceptibility disorder is believed to be inherited as an autosomal dominant. The principal phenotypic marker is multiple colonic adenomas (usually less than 100), with a tendency for proximal location. The majority of these adenomas are flat or slightly raised and plaquelike, as opposed to polypoid. Colon cancers have typically developed in middle age and show no unusual histologic features. There are a variety of extracolonic manifestations, including adenomas and carcinomas of the small bowel and fundic gland polyps. The HFAS is contrasted with hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis (FAP) and shown to be distinct from both in the numbers and distribution of colonic adenomas and the typical age of cancer diagnosis. The clinical implications of these findings are discussed. Given its linkage to the FAP locus on 5q and the phenotypic parallels between HFAS and FAP, we conclude that HFAS is a variant of FAP.

Adenoma↗
PubMed1992

A rationale and framework for establishing the quality of human exposure assessments.

Exposure assessments, performed as input to an evaluation of potential human health risk, are an element of risk assessment. Risk assessment results feed governmental and corporate risk management decisions, which seek to balance the estimated potential human health risks with other factors. Risk managers presume that the risk information provided to them is scientifically valid and accurate. Government agencies have begun to apply a system known as good laboratory practices (GLP) to ensure adequate data quality on animal studies, which are often the first step in the health-effects evaluation of risk assessment. This paper explores a rationale and framework for establishing the quality of human exposure assessments and proposes a set of good exposure assessment practices (GEAP). The components of the proposed GEAP include the writing of a study protocol before conducting the study, consideration of available resources, specification of an exposure model, a study design (including sampling and analytical methods and data analysis), quality assurance, archiving, communications, and a statement of overall uncertainty in exposure estimates. The GEAP concept is offered as a starting point for developing a consensus among the community of exposure assessors regarding a minimum standard for good practices. If a consensus on GEAP can be reached and applied, exposure assessments would have improved scientific bases, interpretability, and utility.

Environmental Monitoring↗
PubMed1992

An industrial hygiene methodology developed in support of a retrospective morbidity case-control study.

An industrial hygiene methodology that was developed in support of an epidemiologic case-control study is described. This study was conducted to investigate a potentially increased incidence of colorectal cancer among employees who worked at a unit that manufactured polypropylene by a heavy diluent process. Retrospective epidemiologic case-control studies typically have exposure assessment problems because industrial hygiene monitoring data are often not available. Misleading job titles are another problem that can provide a poor framework for estimating exposures. In addition, a job title-based exposure assessment assumes individual work patterns are not important in assessing worker exposures, although this is contradictory to industrial hygiene experience. The design of the case-control study provided an innovative industrial hygiene approach to circumvent these typical exposure estimating problems. The industrial hygiene methodology of the case-control study included assessing historical exposures, developing an exposure estimating matrix, selecting candidate etiologic agents based on a joint toxicologic and industrial hygiene review, administering a work activity questionnaire, calculating exposure scores, and conducting a statistical analysis. The study design also provided an additional exposure measurement independent of the toxicologic and industrial hygiene review. This provided an opportunity to compare the likelihood of exposure misclassification and, as expected, showed that a more detailed exposure estimate resulted in less misclassification.

Colorectal Neoplasms↗
PubMed1992

Post-dural puncture headache in young orthopaedic in-patients: comparison of a 0.33 mm (29-gauge) Quincke-type with a 0.7 mm (22-gauge) Whitacre spinal needle in 200 patients.

The incidence of postdural puncture headache (PDPH) following spinal anaesthesia with a 0.33 mm (29-gauge) and two types of 0.7 mm (22-gauge) Whitacre needles was investigated in 400 patients less than 40 years old. The incidence of PDPH was 2% in the 0.33 mm group, and 3.5% in the 0.7 mm group. Headache of other origin was seen in 12 patients (6%) in the 0.33 mm and in five patients (2.5%) in the 0.7 mm group. These differences were not significant. The failure rate was significantly higher in the 0.33 mm group (8.5% vs 2%) than in the 0.7 mm group (P less than 0.05). It is concluded that the 0.33 mm needle is associated with a low incidence of PDPH in young patients, but has a significantly higher failure rate than the Whitacre 0.7 mm needle, which is also a suitable choice in this age-group because of its ease of handling and the low incidence of PDPH.

Adolescent↗
PubMed1992

Brain-death criteria currently used by pediatric intensivists.

A survey was done to identify how pediatric intensivists determine brain death in children. Forty-nine pediatric intensive-care units (PICUs) were surveyed. The questionnaire explored the following areas: 1) clinical and confirmatory studies performed, 2) types of physicians involved, and 3) reevaluation intervals. Thirty-four centers responded to the questionnaire. Sixty-nine percent were children's hospitals, and 94% were university affiliates. The mean number of PICU beds was 17, with a mean admission rate of 890 patients per year, and the mean mortality rate for these units was 6%. There was general agreement on the sufficiency of clinical examination to determine cortical and brain-stem function. All the pediatric intensivists noted that a positive apnea test, absent cephalic reflexes, fixed and dilated pupils, and no motor response to pain were reliable signs of brain death. Radionuclide cerebral-flow scan and EEG were the confirmatory tests routinely used. Most physicians (77%) felt a second clinical examination was required within 12 to 24 hours. The opinion of more than one physician, one of whom was a neurospecialist, was required in 80% of the surveyed institutions.

Blood Flow Velocity↗
PubMed1992

Whitacre 22-gauge pencil-point needle for spinal anaesthesia. A controlled trial in 300 young orthopaedic patients.

In a prospective study of 300 young orthopaedic in-patients (less than 40 years) given spinal anaesthesia through a 22-gauge Whitacre (n = 150) or a 25-gauge Quincke spinal needle (n = 150), we found a 5.3% and a 9.3% incidence of post-spinal headache (PSH) respectively. Females (10.6%) had a higher overall incidence of post-spinal headache than males (5.6%) with more than twice as many females being affected in the 25 than in the 22-gauge group (14.5% vs 6.1%). The average duration of post-spinal headache was less in the 22-gauge group (36 h vs 42.4 h) as was the incidence of severe headache. It is concluded that the Whitacre 22-gauge needle is more suited for spinal analgesia in young female patients due to its ease of handling and its lower incidence of post-spinal headache.

Adolescent↗
PubMed1992

Mivacurium: dose-response relationship and administration by repeated injection or infusion.

The dose-response relationship and neuromuscular blockade after infusion or repeated injection of mivacurium were studied in 65 patients in nitrous oxide-narcotic anesthesia. The ED95 (twitch tension) was determined in 45 patients by intravenous injection of a single bolus of 30, 39, 47, 54, or 60 micrograms/kg (9 patients per dose). Another 20 patients received an initial bolus of 2 x ED95 followed either by an infusion started at 5% twitch recovery (i.e., 95% depression) and adjusted to sustain 95% twitch depression (n = 10) or by repeated injection of 0.6 x ED95 whenever twitch tension had recovered to 25% of control (n = 10). Five patients in each of these two groups received 7 micrograms/kg of neostigmine at 25% twitch recovery, and the others recovered twitch tension spontaneously. The mean ED95 was 73 micrograms/kg. A 2 x ED95 bolus was followed by complete twitch depression within 2.2 +/- 0.7 min. The mean infusion rate resulted in 6 +/- 2 micrograms.kg-1.min-1. The ensuing recovery index was 6 +/- 3 min. A 6 +/- 2 min recovery index was found after up to 10 repeat injections given every 9 +/- 3 min. There was no significant effect of neostigmine in both groups. In conclusion, the recovery indices after the infusion or repeat injection of near-equal doses of mivacurium were identical.

Adolescent↗
PubMed1992

Cardiovascular effects of methamphetamine.

Stimulant abuse has grown in popularity, particularly since the advent of crack cocaine. Another commonly abused drug is methamphetamine (MAP) hydrochloride. Known as crank, crystal, ice, crystal meth, and speed, MAP can be produced easily from ephedrine, and it is widely available. This article describes the pharmacology, cardiovascular effects, and toxicology of MAP, as well as the management principles of MAP abuse.

Cardiovascular Diseases↗
PubMed1991

Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.

Chronic elevation of plasma homocysteine is associated with increased atherogenesis and thrombosis, and can be lowered by betaine (N,N,N-trimethylglycine) treatment which is thought to stimulate activity of the enzyme betaine:homocysteine methyltransferase. We have developed a new assay for this enzyme, in which the products of the enzyme-catalysed reaction between betaine and homocysteine are oxidised by performic acid before being separated and quantified by amino acid analysis. This assay confirmed that human liver contains abundant betaine:homocysteine methyltransferase (33.4 nmol/h/mg protein at 37 degrees C, pH 7.4). Chicken and lamb livers also contain the enzyme, with respective activities of 50.4 and 6.2 nmol/h/mg protein. However, phytohaemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts contained no detectable betaine:homocysteine methyltransferase (less than 1.4 nmol/h/mg protein), even after cells were pre-cultured in media designed to stimulate production of the enzyme. The results emphasize the importance of the liver in mediating the lowering of elevated circulating homocysteine by betaine.

Animals↗
PubMed1991

Familial breast-ovarian cancer locus on chromosome 17q12-q23.

Familial breast cancer has been linked to the D17S74 locus on chromosome 17q. To confirm this finding and to investigate whether ovarian cancer is also linked to this locus, five large families with a hereditary predisposition to cancer of the breast and ovary were investigated. Three families were positive for linkage. For the largest family the lod score was 2.72. These findings suggest that the chromosomal region 17q12-q23, previously shown to contain a gene for early-onset breast cancer, is also associated with a proportion of hereditary ovarian cancers.

Adult↗
PubMed1991

A follow-up study of colonic epithelial proliferation as a biomarker ina Native-American family with hereditary nonpolyposis colon cancer.

A 7-year follow-up study of colonic mucosa proliferation markers was conducted on members of a Native-American family with hereditary nonpolyposis colon cancer. Reproducibility of a tritiated thymidine autoradiography assay for labeling indexes during this 7-year biologically significant time frame was established. A good correlation between tritiated thymidine and a newer technique, bromodeoxyuridine immunoperoxidase staining, was seen. No confounding effect could be attributed to standard colon preparation. On average, both baseline and follow-up values for epithelial proliferation were within the accepted normal range. The presence of essentially normal labeling indexes among colon cancer patients and their high-risk offspring suggests the possibility of the significant effect of dietary factors in reducing proliferation. Such factors may account for the low risk of colon cancer that characterizes the Native-American population in the American Southwest.

Adult↗
PubMed1991

An adenomatous polyp case-control study to assess occupational risk factors following a workplace colorectal cancer cluster.

To assess potential etiologic factors among a population of Texas polypropylene workers previously found to have an excess of colorectal cancer (concentrated among mechanical and process workers), the authors conducted an adenomatous polyp case-control study. Cases (n = 24) were workers found to have adenomatous polyps during a company-sponsored colorectal cancer screening program, while controls (n = 72) were workers found to be free of polyps. Exposure assessment utilized a thorough industrial hygiene and toxicologic review of operations in conjunction with work activity interviews of cases and controls to develop chemical-specific exposure scores weighted by time, exposure level, and frequency of exposure. Stratified analyses and logistic regression found that cases tended to have higher exposure to pre-extrusion polymer plus additives (odds ratio (OR) = 2.6, 90% confidence interval (CI) 1.1-6.3) and higher exposure to certain finishing additives (OR = 4.8, 90% CI 1.5-15.3). Analyses by job category or area of the plant did not indicate additional risk factors. The exposures identified in this study are discussed in light of the available toxicologic data on these and related compounds. The need for confirmatory experimental and epidemiologic studies is noted.

Case-Control Studies↗