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M Gill

Publications and source records attributed to M Gill.

At least 127 records · Page 7Linked to original sources
PubMed1994

Genetic mapping of 14 short tandem repeat polymorphisms on human chromosome 22.

We have constructed a linkage map of 14 short tandem repeat polymorphisms (11 with heterozygosity > 70%) on the long arm of human chromosome 22 using 23 non-CEPH pedigrees. Twelve of the markers could be positioned uniquely with a likelihood of at least 1,000:1, and distributed at an average distance of 6.62 cM (range 1.5-16.1 cM). The sex-combined map covers a total of 79.6 cM, the female map 93.2 cM and the male map 64.6 cM. Based on comparisons between physical maps and other genetic maps, we estimate that our map covers 70%-80% of the chromosome. The map integrates markers from previous genetic maps and uniquely positions one marker (D22S307). Data from physical mapping on the location of four genetic markers correlates well with our linkage map, and provides information on an additional marker (D22S315). This map will facilitate high resolution mapping of additional polymorphic loci and disease genes on chromosome 22, and act as a reference for building and verifying physical maps.

Chromosome Mapping↗
PubMed1994

Renal haemodynamic effects of bunazosin retard and prazosin in mild to moderately hypertensive patients with normal or moderately impaired renal function.

Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured in 53 hypertensive patients (26 renally impaired, 27 with normal renal function) before and after treatment with sufficient bunazosin retard or prazosin to control their high blood pressure. After a 3-week placebo run-in period, patients were classified as normal (creatinine clearance > 80 ml/min) or renally impaired (20-55 ml/min), and randomly assigned to bunazosin retard or prazosin. There followed a dose titration (T) phase of 6-7 weeks, and a maintenance (M) phase of 4 weeks. Blood pressure was satisfactorily controlled (sitting diastolic pressure < or = 90 mmHg or decreased by > or = 10 mmHg) by both drugs in both groups. Bunazosin Retard was associated with increases in GFR and ERPF in both normal and renally impaired groups; the increases were statistically significant in the renally impaired group (n = 14). Prazosin was associated with small decreases in both measures in both groups. One patient died of myocardial infarction during the placebo run-in. There were no other serious adverse events. Four patients reported dizziness (2 with each drug). We conclude that with appropriate dose titration, bunazosin retard is well tolerated and preserves renal blood flow when used to treat hypertension in patients with renal insufficiency.

Adolescent↗
PubMed1994

Magnetic resonance imaging and spectroscopy of small ring-enhancing lesions using a rat glioma model.

RATIONALE AND OBJECTIVES: We sought to demonstrate the usefulness of proton and fluorine magnetic resonance spectroscopy (MRS) techniques in characterizing small ring enhancing lesions produced by experimental malignant gliomas. METHODS: The growth characteristics of a rat glioma model (RT2) were studied using contrast-enhanced magnetic resonance imaging scans of the tumors and histologic correlates obtained at various times. Changes in tumor metabolite levels were monitored on a serial basis using water-suppressed proton spectroscopy. The existence of tumor hypoxia was established using 19F MRS in combination with a fluorinated nitroimidazole and subsequently confirmed by immunohistochemical staining of tumor sections. RESULTS: Ring-enhancing lesions are produced by RT2 rat brain gliomas approximately 7 days after intracerebral implantation. Beginning at day 5, marked deviations in brain metabolite levels are observed on proton MR spectra. However, while the signal from the fluorinated nitroimidazole is first detected by 19F MRS at day 7, immunohistochemical staining of tissue sections reveals bound drug as early as day 5, when the first histologic signs of necrosis become apparent. CONCLUSIONS: Magnetic resonance imaging of RT2 rat brain glioma exhibits ring-enhancing characteristics similar to those observed in clinical studies. The appearance of the ring enhancement corresponds with the development of central necrosis and could serve as an indicator for rapid growth. Proton and fluorine MRS may be useful in confirming that a small ring-enhancing lesion represents an active tumor process early in its development.

Animals↗
PubMed1994

Association and haplotype analysis at the tyrosine hydroxylase locus in a combined German-British sample of manic depressive patients and controls.

Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines and may therefore be of aetiological relevance in the development of psychiatric illness. Hipolar affective disorder association studies, with restriction fragment length polymorphisms located in flanking regions of the TH gene, have shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4) located in intron 1 of the gene were tested for association with bipolar affective disorder in a combined German and British sample of 183 bipolar patients and 209 healthy control probands. No differences in TH4 allele frequencies were found in the two groups. A subset of patients and controls was typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two-locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7 and TH4-pJ4.7. Haplotype frequencies did not differ between patients and controls.

Alleles↗
PubMed1994

Analysis of the conserved Asp(114) residue of the dopamine D2 receptor in schizophrenic patients.

The factors that influence response to antipsychotics treatment in chlorpromazine remain difficult to delineate but are thought to include genetic factors. Site-directed mutagenesis studies have demonstrated that substitution of the conserved residues Asp(113) to an Asn or Glu greatly reduces the binding affinity of propranolol in the beta-adrenergic receptor and the substitution of an Asp(114) has similar effects in the dopamine D2 receptor. In this study we have found the Asp(114) in the dopamine D2 receptor to be unaltered in 72 unrelated schizophrenic individuals including 12 patients classified according to their response to chlorpromazine.

Aspartic Acid↗
PubMed1994

An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in schizophrenia.

The cytochrome P450 mono-oxygenases are a group of enzymes that metabolize a variety of exogenous and endogenous compounds, some of which are potentially toxic. Individual variations in the metabolism of potential toxins could influence susceptibility to disorders having genetic and environmental components, such as schizophrenia. The frequency of two common mutant alleles of the gene for the cytochrome P450 enzyme debrisoquine-4-hydroxylase (CYP2D6) was determined in 264 Caucasian schizophrenic patients and 217 controls, using the polymerase chain reaction and restriction enzyme digestions. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and the frequency of each mutant allele (CYP2D6A and CYP2D6B) did not differ between patients and controls.

Alleles↗
PubMed1994

Postal self-exposure treatment of recurrent nightmares.

BACKGROUND: Case reports suggest that recurrent nightmares are alleviated by behavioural treatment. We have administered such treatment to a client by post. METHOD: The frequency of nightmares was recorded by the client before and during treatment, and at one and six months follow-up. Nightmare problem and target scales, and treatment expectation were recorded at the end of each period. Treatment was by rehearsal relief, self-administered using written instructions. RESULTS: A reduction in nightmare frequency from 5.5 per week in the baseline period to an average of one per week resulted after treatment. CONCLUSIONS: The client's chronic nightmares were lastingly relieved after self-administered exposure treatment. A controlled trial is underway.

Adult↗
PubMed1994

Functional neuroimaging and pharmacogenetic studies of clozapine's action at dopamine receptors.

The factors that influence response to neuroleptic drugs are poorly understood. These factors may include clinical variables such as length of illness before treatment, age at onset, and the presence of negative symptoms; and pharmacologic factors such as rates of drug metabolism. For example, pharmacodynamic differences in therapeutic response to haloperidol have been observed between Chinese and Caucasian patients. Response rates may also reflect clinical heterogeneity, although familiality, history of obstetric trauma, or ventricular enlargement have been not shown to be significant factors. It is also possible that genetic differences in receptors that are targets for these drugs may influence response.

Adult↗
PubMed1994

Single-dose cefuroxime versus multiple-dose cefazolin as prophylactic therapy for high-risk cholecystectomy.

The ideal regimen for the prevention of postoperative infections occurring after elective cholecystectomy has been widely debated. This double-blind, randomized study was conducted to compare the effectiveness and safety of cefuroxime with that of cefazolin in 295 patients undergoing elective cholecystectomy who were considered to be at high risk for postoperative infection. Patients were randomly assigned to receive either a single 1.5 gram dose of cefuroxime plus three doses of placebo, or four 1 gram doses of cefazolin. Each regimen was begun 30 to 60 minutes preoperatively and repeated every six hours for three doses postoperatively. Patients were evaluated during the hospitalization period and again at 30 days. All postoperative infections, including remote infections, were included in the definition of failure. Bacteriologic success rates were 95.5 percent in the cefuroxime group and 98.2 percent in the cefazolin group (p > 0.05). Corresponding clinical success rates were 91.4 and 94.9 percent (p > 0.05), respectively. There was no association between intraoperative bile cultures and the risk of failure or the type of microorganism isolated from postoperative infections. Both regimens were well-tolerated. In view of the additional costs and time associated with preparation and administration of multiple doses, a single preoperative 1.5 gram dose of cefuroxime may be a cost-effective alternative to four 1 gram doses of cefazolin in patients undergoing elective cholecystectomy who are at high risk for postoperative infection.

Cefazolin↗
PubMed1993

Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees.

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity.

Female↗
PubMed1993

Failure to find linkage between schizophrenia and genetic markers on chromosome 21.

We sought evidence for the involvement of mutations in the amyloid precursor protein gene (APP) in the pathogenesis of schizophrenia in two ways. First, linkage analysis was performed in a sample of 24 families multiply affected with schizophrenia. The genotypes were studied for GT12 (D21S210), a highly polymorphic microsatellite marker at the APP locus. Second, we used single strand conformation analysis (SSCA) to screen for mutations in exon 17 of APP in one affected member from each family and in a sample of 44 unrelated patients. In addition, we looked for linkage between schizophrenia and a series of highly polymorphic markers situated at approximately 20cM intervals along the long arm of chromosome 21. We were unable to find evidence for linkage to GT12 or the other markers studied. SSCA did not reveal any mutations in exon 17 of AP. We conclude that mutations within APP are an unlikely cause of schizophrenia. Moreover, this study provides no evidence for a major gene for schizophrenia on chromosome 21, and linkage can be excluded from much of this region under some genetic models.

Adult↗