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Biomedical subjects

M Gill

Publications and source records attributed to M Gill.

At least 145 records · Page 8Linked to original sources
PubMed1993

Schizophrenia: genetics and the maternal immune response to viral infection.

Thirty years ago, Eliot Slater suggested that the reason schizophrenia was not progressively eliminated from the population was that the responsible gene also conveyed a compensatory advantage in terms of increased resistance to infection. If this selective advantage lies in the antibody response to certain viral infections, this could explain recent studies suggesting that exposure to influenza in the second trimester of gestation increases the risk of later schizophrenia. We propose that prenatal exposure to influenza induces maternal antibodies which then cross-react with proteins in the developing foetal brain, becoming foetal autoantibodies. Thus an immunogenetic response by the mother results in aberrant foetal neurodevelopment, the biological substrate for a proportion of adult schizophrenia. Initial research strategies to test this hypothesis are proposed.

Antibodies, Viral↗
PubMed1993

A continuous linkage map of 22 short tandem repeat polymorphisms on human chromosome 12.

A continuous linkage map consisting of 22 short tandem repeat polymorphisms has been constructed for human chromosome 12 using 23 non-CEPH pedigrees. The markers were distributed at an average distance of 9.35 cM (3.1-33.9 cM). Eighteen of the markers could be positioned uniquely with a likelihood of > 1000:1. The physical locations of some of the markers suggest that the map covers 85-95% of the chromosome. This framework map of 18 markers has a female length of 213 cM and a male length of 131 cM. Female recombination frequencies were greater than male recombination frequencies except in the distal portion of the short arm. The map provides confirmatory evidence for orders established previously on CEPH pedigrees and uniquely positions 4 additional markers (CD4, ATPSB, D12S56, PLA2).

Chromosome Mapping↗
PubMed1993

A study of the association between schizophrenia and the dopamine D3 receptor gene.

A study of the genetic association between schizophrenia and a BalI polymorphism in exon 1 of the dopamine D3 (DRD3) gene, a candidate gene for schizophrenia, was conducted. The polymorphism was examined in 91 patients whose symptoms satisfied DSM-III-R for schizophrenia and 90 controls. There were no significant differences between the groups in allele frequencies or genotype counts. Contrary to a previous report, the patients were no more likely to be homozygous than controls. Moreover, no association with the presence of illness could be demonstrated when the patients were grouped according to sex, age of onset, history of admission to psychiatric institutions or positive family history.

Adult↗
PubMed1993

Comparative bronchoalveolar concentrations of ciprofloxacin and lomefloxacin following oral administration.

In a comparative study, the concentrations of two fluoroquinolone antimicrobials, ciprofloxacin and lomefloxacin, were measured in serum, bronchial mucosal biopsies, epithelial lining fluid (ELF) and alveolar macrophages (AM). Thirty-four subjects received either ciprofloxacin 250 mg b.d. (17 subjects) or lomefloxacin 400 mg o.d. for 4 days prior to sampling by bronchoscopic bronchial biopsy and bronchoalveolar lavage. Both ciprofloxacin and lomefloxacin showed favourable accumulation in the sites of infection with bronchial biopsy concentrations of 1.6 and 1.7 times those of serum respectively; ELF concentrations of 2.1 and 1.9 times serum; and AM concentrations of 11.8 and 20.1 times serum respectively. The MIC90 for most of the common chest pathogens was reliably exceeded by both agents except for that of Streptococcus pneumoniae.

Administration, Oral↗
PubMed1993

A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11.

We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis-specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease.

Alleles↗
PubMed1993

Examination of energy utilization in cattle offered a forage diet at near- and sub-maintenance levels of feeding.

Eight Friesian calves were reared from birth to the start of the experiment at a predetermined growth rate of 1.0 kg/d. Four calves (group 1) commenced the experiment at 22 weeks of age and the remainder (group 2) at 34 weeks, and feed intake was calculated to provide sufficient metabolizable energy to sustain zero energy balance (Em). Between experimental days 30 and 56 at maintenance levels of feeding, respiratory exchange measurements were made using open-circuit calorimetry to provide indirect estimates of heat production (H) simultaneous with measurements of faecal and urinary excretion of energy and N. A datum point for Em and H was established for each animal giving mean values for Em of 491 and 537 and for H of 476 and 511 kJ/kg live weight (LW)0.75 per d for groups 1 and 2 respectively. Treatment levels calculated as 0.25, 0.5, 0.75 and 1.25 of dry matter intake required to sustain the measured Em, were imposed on individual animals after day 56 and further measurements of H and faecal/urinary balance were made between days 72 and 84 followed by measurements of fasting heat production (FHP) during days 86-90 from the two animals in each group which had received the 0.75 and 1.25 levels of intake. Regression analysis of the treatment levels indicated separate linear models which predicted Em at 419 and 473 kJ/kg LW0.75 per d for groups 1 and 2 respectively. The incorporation of FHP with partitioning of faecal and urinary energy losses measured during fasting altered the relationship but not the predicted Em. Overall predicted Em (days 72-84) from all models were 406 and 478 kJ/kg LW0.75 per d for groups 1 and 2 respectively which were significantly lower (P < 0.05) than Em measured during days 30-56.

Animals↗
PubMed1993

The gene for Darier's disease maps to chromosome 12q23-q24.1.

Darier's disease is a rare autosomal dominant skin disorder in which there is abnormal adhesion between keratinocytes. It appears to be associated with an increased prevalence of neuropsychiatric disorders including mental retardation and epilepsy. In addition we have previously reported a family in which major affective disorder cosegregates with Darier's disease. In the present study we have localized the gene for Darier's disease to chromosome 12q23-q24.1 by linkage analysis in five British pedigrees. We obtained a maximum two point lod score of 4.29 with marker D12S84 at zero recombination fraction. All five families showed evidence of linkage between the disease gene and markers in this region. Subsequent identification of the Darier's disease gene will provide insights into normal mechanisms of cell adhesion and may be of importance in the genetic investigation of neuropsychiatric disorders as well as elucidating the pathogenesis of Darier's disease itself.

Chromosome Mapping↗
PubMed1993

Cosegregation of schizophrenia with Becker muscular dystrophy: susceptibility locus for schizophrenia at Xp21 or an effect of the dystrophin gene in the brain?

A family is reported in which four of five adult patients with Becker muscular dystrophy (BMD) also have schizophrenia or related spectrum disorders. Although the estimated lod scores are not sufficient to conclude the existence of linkage between BMD and schizophrenia, it is suggested that there may be an association between these two disorders. Two alternative hypotheses are proposed to explain such an association: (1) the existence of a susceptibility locus for schizophrenia and spectrum disorders on the short arm of the X chromosome at Xp21; (2) that these psychiatric disorders may result from an abnormality in the expression of the dystrophin gene in the brain.

Adult↗
PubMed1993

The dopamine D3 receptor gene: no association with bipolar affective disorder.

Bipolar affective disorder and schizophrenia share many clinical and genetic characteristics, and are thought by some to be different expressions of the same underlying disorder. A recent study showed an excess of homozygosity at a BalI polymorphism in the dopamine D3 receptor gene in schizophrenic patients compared with controls, from two independent centres. We have found no evidence of such an excess in a comparable sample of patients with bipolar affective disorder compared with matched controls. If these findings are confirmed then at least one genetic distinction between these two disorders will have been ascertained and doubt cast upon theories of a common genetic aetiology.

Alleles↗
PubMed1993

Prospective randomized study of two different doses of clindamycin admixed with gentamicin in the management of perforated appendicitis.

Septic complications after surgery for enterogenous peritonitis are minimized by adjuvant antibiotics effective against aerobes and anaerobes. Historically, "gold standard" therapy included an aminoglycoside plus clindamycin, the latter given at 600 mg intravenous piggyback (IVPB), every 6 hours. Clindamycin pharmacokinetics suggests that it can be given q8h and admixed with gentamicin, thereby markedly reducing the cost of administration. Although this is now common practice, there is no prospective study comparing the efficacy of the two dose schedules in peritonitis. This study was designed to test the hypothesis regarding the clinical efficacy of the two regimens. One hundred twenty-six patients with gangrenous (n = 34) or perforated appendicitis (n = 91) were randomized (2:1) to receive gentamicin admixed with clindamycin 900 mg IVPB every 8 hours (Group I n = 80) or gentamicin IVPB q8h plus clindamycin 600 mg IVPB every 6 hours (Group II n = 46). Appendectomy was performed, and aerobic and anaerobic cultures were obtained. Twenty-one patients had simultaneous determinations of clindamycin levels in plasma, peritoneal fluid, and appendix. Outcome analysis revealed no significant differences in postoperative days of fever, days non per os, antibiotic therapy, or hospitalization. There were 6 failures (4 abscesses and 2 wound infections) in Group I and 4 failures (1 abscess and 3 wound infections) in Group II. Both antibiotic regimens provided clinically equivalent results in mixed infections due to aerobic and anaerobic bacteria. The admixed clindamycin, administered every 8 hours, results in at least 20% reduction in costs. This is an important consideration.

Adult↗
PubMed1992

Survival in extreme dryness and DNA-single-strand breaks.

A wide variety of organisms (the so-called "anhydrobiotes') is able to survive long periods of time in a state of utmost dehydration and can thus survive in extremely dry environments including artificially imposed or space vacuum. Known strategies of survival include the accumulation of certain polyols, especially disaccharides, which help prevent damage to membranes and proteins. Here we report that DNA in vacuum-dried spores is damaged to a very substantial degree by processes leading to DNA strand breaks. Most of these lesions are obviously repaired during germination, but extensive damage to DNA and enzymes after long exposure times (months to years) finally diminish the chances of survival.

Autoradiography↗
PubMed1992

Variations in breast cancer management between a teaching and a non-teaching district.

We compared the management and outcome of 999 women with breast cancer presenting between 1982 and 1986 at two centres in a region, one in a teaching district. A comparison was also made with relevant research and The Kings Fund Consensus Statement. The centres frequently differed markedly in the investigations done, diagnostic procedures, histology reporting, axillary sampling, and in the treatment given, also differing from the Consensus with no trend towards it. Survival was better at the teaching centre, both disease-free (N.S.) and overall [odds ratio 1.46 (1.16-1.84) P = 0.0009 unadjusted]. This should be interpreted cautiously as the median follow-up time was relatively short and the study was non-randomised. We conclude that how women with breast cancer are managed is determined as much by where they are referred as by scientific evidence. This indicates the need to introduce standards and protocols into business plans, making audit and service specifications easier.

Aged↗