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Biomedical subjects

M Gill

Publications and source records attributed to M Gill.

At least 19 recordsLinked to original sources

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

Alleles

Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.

Alleles

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

Studies of method of conserving grass herbage and frequency of feeding in cattle. 1. Voluntary feed intake, digestion and rate of passage.

The effect of method of conserving grass herbage and the frequency of feeding on digestion in and passage from the rumen was studied in growing cattle. A single sward of perennial ryegrass (Lolium perenne cv. Endura) was cut on 1 d and conserved as silage or hay. These forages were offered as the only feed to twelve rumen-cannulated Friesian steers (average initial live weight (LW) 128 kg) either at a restricted level of intake (20 g dry matter (DM)/kg LW; Expt 1) or ad lib. (Expt 2). In Expt 1 the forages were offered either once or eight times daily. When fed once or eight times daily, in vivo digestibility of DM was very similar for hay and silage (0.771 and 0.783 respectively), while the fractional rate of digestion measured by incubation in Dacron bags was significantly (P less than 0.05) higher for silage (0.069) than hay (0.057). The rate of passage of mordanted feed out of the rumen was significantly (P less than 0.01) faster for silage when determined from concentrations of marker in the rumen (0.034 v. 0.028/h). The volume of liquid in the rumen was lower (P less than 0.01) for animals consuming silage (27.51) compared with hay (37.11), while the fractional rate of passage of liquid from the rumen was higher (0.141 v. 0.098/h, P less than 0.05). The volume of liquid in the rumen was also lower (P less than 0.05) in steers offered feed eight times daily (29.5 l), compared with once daily (35.1 l), but frequency of feeding had no significant effect either on total digestibility or on rate of digestion in the rumen. The ad lib. intake of silage was significantly (P less than 0.01) lower than that of hay (4.53 v. 5.16 kg DM/d) in Expt 2.

Animal Feed

Studies of method of conserving grass herbage and frequency of feeding in cattle. 2. Eating behaviour, rumen motility and rumen fill.

The influence of the method of conserving grass herbage and the frequency of feeding on eating behaviour, rumen motility and rumen fill was studied in growing steers. Silage and hay were offered to twelve rumen-cannulated Friesian steers (average initial live weight (LW) 128 kg) at a restricted level of intake (20 g dry matter (DM)/kg LW) either once or eight times daily. With once daily feeding, the daily intake of hay was consumed in a single large meal which lasted about 2 h, while silage was eaten in many small meals throughout the day. The proportion of the day spent ruminating was higher (0.39) for steers offered hay once daily than for those offered silage (0.28) or hay eight times per day (0.29). There was little effect of conservation method on frequency of rumen contraction, but contractile intensity (integration of frequency and amplitude) increased during the second half of the 24 h feeding cycle in steers offered hay either once daily or eight times daily, while the same effect was only observed when silage was offered once daily. Total daily contractile activity (the integration of the frequency and duration of myoelectric spike bursts) was significantly (P less than 0.05) higher in steers offered hay, compared with silage, once daily. The mean weight of organic matter in the reticulo-rumen of steers offered hay was significantly higher than for silage both with once (1593 v. 1326 g organic matter (OM)/100 kg LW, P less than 0.01) and eight (1367 v. 1160 g OM/100 kg LW, P less than 0.05) times daily feeding. The proportion of the particulate pool which was present as small (less than 1.2 mm) particles was always greater than 0.60.

Animals

Simulation of nutrient digestion, absorption and outflow in the rumen: model evaluation.

A mathematical model of the rumen fermentation processes constructed to predict nutrient supply to the host animal was evaluated. Sensitivity analysis on high fiber, starch and protein diets indicated that the model responds appropriately to these types of diets and to changes in parameter values, and revealed that the model is sensitive to the availability of hexose for non-growth microbial processes and to the maximum storage rate of polysaccharides in amylolytic microbes, although sensitivity varied with diet composition. Of the parameters whose values were dependent on diet, the fraction of protozoa in the amylolytic microbial pool and the fluid and solid passage rates needed the most careful estimation. When model predictions of nutrient supply were compared with the experimental observations, those for duodenal flows of neutral detergent fiber, total non-ammonia nitrogen (NAN) and total volatile fatty acid rumen concentration were satisfactory for several feeding strategies. The partition of NAN flow into microbial and non-microbial NAN flow and the molar proportions of volatile fatty acid production and concentration were not predicted well. The representation of the complex interactions between rumen microbial populations and of their effects on the production of specific volatile fatty acids merits further study for an improvement in the prediction of nutrient supply.

Absorption

Linkage study of schizophrenia with markers on chromosome 11 in two Japanese pedigrees.

We examined the linkage between schizophrenia and DNA markers on chromosome 11 in two Japanese pedigrees. Thirty individuals from the two pedigrees were genotyped at the eleven polymorphisms (eight loci) studied. Data were analyzed according to three models, representing a range of single gene models from near dominant to an intermediate model. For all markers, except those at the D11S35 locus, there is no evidence for the linkage. Positive LOD scores between 1 and 1.5 are obtained for some genetic models with the polymorphism at D11S35. Two point scores for the broad diagnostic model and for the intermediate parameter set peak at 1.49.

Chromosome Mapping

Correlation of various in vitro testing methods with clinical outcomes in patients with Bacteroides fragilis group infections treated with cefoxitin: a retrospective analysis.

There is limited information regarding the correlation of anaerobic susceptibility testing and outcome in the treatment of Bacteroides fragilis infections. We retrospectively analyzed the clinical outcomes of B. fragilis infections in patients treated with cefoxitin; the analysis was blinded for susceptibility results. Isolates of B. fragilis were tested by multiple agar dilution methods, disk elution, and commercial broth microdilution methods. Of 19 patients analyzed, 11 were cured and 8 were treatment failures. No significant differences existed between the groups with respect to age, sex distribution, weight, APACHE II score, dose of cefoxitin, or bacteremia. Failure was associated with a longer cefoxitin dosing interval (P = 0.019), a longer duration of hospitalization (P = 0.038), and decreased duration of cefoxitin treatment (P = 0.05). Four agar dilution systems (brucella plus blood, Wilkins-Chalgren, Wilkins-Chalgren plus blood, brain heart infusion plus blood) and two broth systems (Wilkins-Chalgren microdilution and a commercial system [Micromedia; Beckman, Carlsbad, Calif.]) all demonstrated lower geometric mean MICs for isolates from the group of patients that could be cured. Only the commercial broth microdilution medium (Micromedia) demonstrated a significantly reduced geometric mean MIC (P = 0.056). By using a logistic regression analysis, the shorter cefoxitin dosing interval (P = 0.0004) and the lower geometric mean MIC (P = 0.0088) in the commercial broth microdilution system were shown to be independent predictors of treatment success. These data suggest that the time that the concentration of cefoxitin is over the MIC for B. fragilis may be an important predictor of treatment success.

Adult

No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families.

Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism.

Blotting, Southern

A mathematical integration of energy and amino acid metabolism of lactating sows.

A dynamic mathematical model of energy and protein metabolism of lactating sows is described in this article. The model is designed to contribute to a systematic and quantitative understanding of the biological connection between diet and reproduction. It traces the flow of energy-containing nutrients from absorption through intermediary metabolism, into and out of body stores, and into milk. State variables (pools) include lysine, other amino acids, glucose, fatty acids, acetate, propionate, acetyl-coenzyme A, ATP, oxygen, carbon dioxide, urea, lean-body protein, visceral protein, storage triacylglycerol, milk protein, milk triacylglycerol, and milk lactose. The rate of each transaction is a function of substrate and inhibitor concentrations, assuming saturable kinetics. Protein and fat turnover, substrate cycles, and the energy cost of membrane transport are explicitly considered. Dynamic simulation of a complete lactation is accomplished by iterating the numerical integration of 16 first-order, nonlinear differential equations, each associated with a pool. Most kinetic parameters were estimated indirectly. Preliminary tests suggest the model is sound. It promises to be useful as a research tool and, with further development, as a guide to practical feeding strategies.

Absorption

Evaluation of a mathematical model of lactating sow metabolism.

A mathematical model of lactating sow metabolism was evaluated using three types of tests. First, 16 experimental treatments from four experiments reported in the literature were simulated with the model, and the simulated values for change in BW and protein and fat content were compared to reported or calculated values. Second, the model's response to level of feed intake, level of milk production, BW and composition at farrowing, and dietary lysine concentration was compared to expected responses. Third, the model's sensitivity to changes in several of its kinetic parameters was measured. There was good agreement between simulated and measured values for BW and fat loss and reasonable agreement for body protein loss. All responses to changes in external conditions were in expected directions and biologically reasonable. The model seemed rather robust with respect to changes in the kinetic parameters considered, although important changes in simulated values were found in some cases. Overall, the model seems sound. It can be useful in evaluation of feeding programs and in understanding biological relationships.

Adipose Tissue

Evaluation of a fluorinated 2-nitroimidazole binding to hypoxic cells in tumor-bearing rats by 19F magnetic resonance spectroscopy and immunohistochemistry.

We have examined a hexafluorinated 2-nitroimidazole, CCI-103F, as a probe for hypoxic tumor cells by in vivo 19F magnetic resonance spectroscopy (MRS). Following initial intraperitoneal injections of the drug in tumor-bearing (Dunning R3327-AT1-Matlylu) rats, 19F spectra were obtained on an Otsuka 2.0T Vivospec spectrometer using a 1.5-cm surface coil. Signal at 1- and 2-h time points indicated initial biodistribution of drug in the tumor. At 4 and 8 h, a progressive increase in signal intensity was observed, indicating retention of drug within the tumor. Tumor signal remained detectable in 4 of 10 rats at 24 h, indicating possible nitroreductive bioactivation by hypoxic cells. Immunohistochemistry of these tumors revealed a staining pattern consistent with labeling of hypoxic cells. No detectable 19F signal was found at 24 h for the other rats, indicating complete washout of unbound drug. Immunohistochemical assessment of these tumors revealed some staining for bound drug at the periphery of necrotic zones. 31P-MRS of the tumors showed good correlation with the presence or absence of hypoxia as evaluated by 19F-MRS, T1- and T2-weighted images, and immunohistochemistry. These results provide the groundwork for further studies using this misonidazole analog for noninvasive identification of hypoxic tumor cells in vivo by MRS.

Adenocarcinoma

Utilisation by homeless people of acute hospital services in London.

OBJECTIVES: To estimate the numbers and distribution of homeless people in London; to quantify the utilisation of acute inpatient services by homeless people in two health authorities; and to predict the total numbers of admissions in homeless people in district health authorities across London. DESIGN: Data were collected from various sources on the distribution of homeless people across London boroughs. All unplanned acute inpatient admissions during November 1990 to relevant hospitals were identified. SETTING: Bloomsbury and Paddington and North Kensington, two former inner London district health authorities. SUBJECTS: Homeless people in London residing in bed and breakfast and private sector leased accommodation, residing in hostels, and of no fixed abode. MAIN OUTCOME MEASURES: Number and cost of acute unplanned admissions in homeless people in two health authorities in November 1990; predicted number of such admissions each year in district health authorities in London. RESULTS: There were at least 60,000 homeless people in London in March 1990. The majority were housed in temporary accommodation (55,412). There were at least 3295 hostel dwellers and 651 people sleeping rough. Homeless people accounted for 105 (8%) of the 1256 acute unbooked admissions in residents of Bloomsbury and Paddington and North Kensington health authorities in November 1990. Considerable variations in the pattern of acute unplanned admissions in homeless people were observed in the two districts with respect to housing status and specialty of admission. The total number of acute unplanned admissions in homeless people across London each year was estimated at 7598, ranging from 38 in Bexley to 1515 in Parkside. CONCLUSIONS: The results have fundamental implications for resource allocation across London. Allocation must take better account of the heterogeneity, uneven distribution, and extra health needs of homeless people.

Adolescent