Family secrets. Most patients speak more freely when on their own.
Explore the source record for details and available documents.
Confidentiality↗
Biomedical subjects
A Barnett
Publications and source records attributed to A Barnett.
Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18q21.
Type 1 diabetes is a common polygenic disease. Fine mapping of polygenes by affected sibpair linkage analysis is not practical and allelic association or linkage disequilibrium mapping will have to be employed to attempt to detect founder chromosomes. Given prior evidence of linkage of the Jk-D18S64 region of chromosome 18q12-q21 to type 1 diabetes, we evaluated the 12 informative microsatellite markers in the region for linkage with disease by the transmission disequilibrium test (TDT) in a UK data set of type 1 diabetic families (n = 195). Increased transmission of allele 4 of marker D18S487 to affected children was detected (P = 0.02). Support for this was extended in a total of 1067 families from four different countries by isolating, and evaluating by the TDT, two novel microsatellites within 70 kb of D18S487. Evidence for linkage and association was P = 5 x 10(-5) and 3 x 10(-4), respectively. There was no evidence for increased transmission of associated alleles to nonaffected siblings. Analysis of an additional 390 families by the TDT did not extend the evidence further, and reduced support in the total 1457 families to P = 0.001 for linkage and P = 0.003 for association. However, evidence for linkage by affected sibpair allele sharing was strong (P = 3.2 x 10(-5)) in the second data set. Heterogeneity in TDT results between data sets was, in part, accounted for by the presence of more than one common disease-associated haplotype (allelic heterogeneity) which confounds the analysis of individual alleles by the TDT. Guidelines for strategies for the mapping of polygenes are suggested with the emphasis on collections of large numbers of families from multiple populations that should be as genetically homogeneous as possible.
Adolescent↗
Evidence for a type 1 diabetes susceptibility locus (IDDM10) on human chromosome 10p11-q11.
A region of linkage to type 1 diabetes has been defined on human chromosome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected sibpairs and a 1 cM resolution microsatellite marker map. Analysis by the transmission disequilibrium test (TDT) in 1159 families with at least one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006, Pc = 0.17). Notably, 5.1 cM distal to D10S193, marker D10S588 also provided positive TDT results (P = 0.009, Pc = 0.25) but the allele under analysis was also preferentially transmitted to nonaffected siblings (P = 0.0008, Pc = 0.02). This allele was positively associated in an independent UK case control study and, importantly, was neutrally transmitted in control CEPH families. These results suggest a type 1 diabetes susceptibility locus on chromosome 10p11-q11 (provisionally designated IDDM10) and demonstrate the necessity of analysis of non affected siblings in disease families, as well as analysis of control families.
Adolescent↗
The molecular basis of the Kidd blood group polymorphism and its lack of association with type 1 diabetes susceptibility.
The Kidd blood group locus encodes a urea transporter which is expressed on human red cells and in the kidney. This gene is located on chromosome 18q12, and evidence for linkage and association with type 1 diabetes mellitus has been reported. To investigate this further, the genetic basis for the blood group Jk(a)/Jk(b) polymorphism was first determined by sequencing reverse-transcribed reticulocyte RNAs from Jk(a+b-) and Jk(a-b+) donors. The Jk(a)/Jk(b) polymorphism was caused by a transition (G838A), resulting in a Asp280Asn amino acid substitution and an MnlI restriction fragment length polymorphism (RFLP). Using the MnlI RFLP, we found that the Jk(a)/Jk(b) polymorphism was not in linkage disequilibrium with type 1 diabetes in 228 multiplex UK and US families tested.
Adolescent↗
High temporal resolution diffusion MRI of global cerebral ischemia and reperfusion.
Although brain ischemia has been extensively studied using diffusion-weighted magnetic resonance imaging, most studies performed so far have not had adequate time resolution to follow the temporal changes in the water apparent diffusion coefficient (ADC) in hyperacute ischemia. Using diffusion echo planar imaging, we obtained ADC maps (calculated from measurements made with 8 b-values) with a time resolution of 43 s in a feline model of global brain ischemia and reperfusion. Different protocols were performed: 10-min hypoperfusion, 10- and 22-min ischemia followed by reperfusion, and cardiac arrest. ADC values were obtained from white matter of the internal capsule and from the thalamus. Cortical gray matter measurements were not deemed reliable due to the close proximity of CSF in the cortical sulci. Following occlusion, the ADC declined in the thalamus to < 2 SD of its normal baseline value within 1.5-2.5 min. This decay was exponential with a time constant (tau +/- SD) of 6.0 +/- 2.6 min; no further decrease in the ADC was observed 10 min following ischemia. Following reperfusion, in animals that showed ADC recovery, the ADC began increasing immediately, returning to its preischemic value in approximately 15 min. No significant ADC changes were observed during hypoperfusion. Following cardiac arrest, the decay of ADC was more rapid in the thalamus (tau = 2.6 +/- 0.6 min) than in white matter (tau = 6.6 +/- 1.8 min). We observed that the ADC at 40 min after cardiac arrest was similar to the ADC at 10 min after ischemia. Given that all animals subjected to 10-min ischemic episodes showed ADC recovery with reperfusion, doubt is cast on whether it is possible to define a threshold value of the ADC below which brain tissue is irreversibly damaged. Finally, despite variability in the time constants of the ADC decay induced by ischemia, the ADC values at 10 min were very similar in all the animals. This suggests that when blood flow is diminished sufficiently to induce an ADC reduction, differences in perfusion affect the rapidity of the decrease but not the final asymptotic value reached.
Animals↗
Diffusion tensor MR imaging of the human brain.
PURPOSE: To assess intrinsic properties of water diffusion in normal human brain by using quantitative parameters derived from the diffusion tensor, D, which are insensitive to patient orientation. MATERIALS AND METHODS: Maps of the principal diffusivities of D, of Trace(D), and of diffusion anisotropy indices were calculated in eight healthy adults from 31 multisection, interleaved echo-planar diffusion-weighted images acquired in about 25 minutes. RESULTS: No statistically significant differences in Trace(D) (approximately 2,100 x 10(-6) mm2/sec) were found within normal brain parenchyma, except in the cortex, where Trace(D) was higher. Diffusion anisotropy varied widely among different white matter regions, reflecting differences in fiber-tract architecture. In the corpus callosum and pyramidal tracts, the ratio of parallel to perpendicular diffusivities was approximately threefold higher than previously reported, and diffusion appeared cylindrically symmetric. However, in other white matter regions, particularly in the centrum semiovale, diffusion anisotropy was low, and cylindrical symmetry was not observed. Maps of parameters derived from D were also used to segment tissues based on their diffusion properties. CONCLUSION: A quantitative characterization of water diffusion in anisotropic, heterogeneously oriented tissues is clinically feasible. This should improve the neuroradiologic assessment of a variety of gray and white matter disorders.
Adult↗
Effectiveness of doxycycline combined with primaquine for malaria prophylaxis.
OBJECTIVE: To assess the causal prophylactic activity (activity against the pre-erythrocytic liver stage) of a daily regimen of doxycycline combined with low dose primaquine against malaria in Australian Defence Force personnel deployed to Papua New Guinea (PNG). PARTICIPANTS AND SETTING: A 53-strong Australian Army engineer detachment deployed to the north coast of PNG for 42 days starting in July 1993. INTERVENTIONS: The soldiers took doxycycline (100 mg) and primaquine (7.5 mg) daily, starting at least two days before they entered the endemic area and continuing for three days after their return to Australia. No primaquine eradication course was given at that time. MAIN OUTCOME MEASURES: The number of soldiers who developed malaria, plasma drug concentrations and drug side effects. RESULTS: None of the 53 men developed malaria while in PNG. Three developed falciparum malaria two to three weeks after leaving the endemic area, although one of them had taken doxycycline alone because of glucose-6-phosphate dehydrogenase deficiency. Nine men developed vivax malaria between three and 40 weeks after leaving PNG, and three had relapses. Doxycycline was generally well tolerated, with only three of the men requiring a change of medication to mefloquine because of adverse gastrointestinal symptoms. CONCLUSIONS: Although doxycycline generally provides good protection against malaria infection, it cannot be relied on for causal prophylaxis, even when combined with low dose primaquine. Because the malaria infections occurred only after return to Australia, doxycycline appears to be effective in suppressing malaria while the drug is being taken. Intense, repeated exposure to malaria may require an extended period of chemoprophylaxis on return from an endemic area.
Australia↗
Integration leader Friendly Hills switches models--again. Interview by Terese Hudson.
The Friendly Hills HealthCare Network keeps moving forward along the leading edge of systems integration, and making headlines in the process. In 1993, it became the first physician-driven integrated delivery system to have its tax-exempt status approved by the Internal Revenue Service. This year, the La Habra, CA-based network took the health care field by surprise when it struck a deal to sell its assets to Caremark International, a nationwide alternate-site provider with a diverse portfolio of services. The purchase, expected to be finalized by the end of the year, will turn Friendly Hills back into a for-profit entity. Chairman and CEO Albert E. Barnett, N.D., spoke recently with senior editor Terese Hudson about the change.
California↗
Selective antagonism of the anticonvulsant effects of felbamate by glycine.
Glycine blocked the anticonvulsant effects of felbamate on electroshock- and NMDA-induced seizures in mice. In contrast to its effects on felbamate, glycine either potentiated or had no effect on the anticonvulsant actions of phenytoin, valproate, carbamazepine and phenobarbital on electroshock seizures in mice. The data support that the glycine-felbamate blockade is a specific interaction. Felbamate is likely to be the first clinically available anticonvulsant drug that acts through this unique mechanism.
Animals↗
Evaluation of the CNS properties of SCH 29851, a potential non-sedating antihistamine. 1984.
Explore the source record for details and available documents.
Animals↗
Visuospatial difficulties and clumsiness: on the interpretation of conjoined deficits.
Sixteen children with motor difficulties and 16 controls, matched on age, gender and verbal I.Q., were assessed on the Test Of Motor Impairment, various graphic tasks and a measure of visuospatial discrimination. Poor perceptual and motor performance tended to co-occur but contrary to the visuospatial deficit account of clumsiness these abilities were uncorrelated even when attention was restricted to the less proficient children. There was no tendency for the control group's superiority in graphic reproduction to diminish when visual feedback was withheld. Some suggestions are offered concerning more appropriate methods for framing and testing causal deficit hypotheses.
Aptitude↗
Response of unacclimatized males to repeated weekly bouts of exercise in the heat.
The purpose of the present study was to determine if there is an acclimation effect when unacclimatized males exercise in the heat at weekly intervals. Five subjects performed four exercise bouts, each lasting 1 h at 55% VO2max. The first trial was in moderate conditions (mean(s.d.) temperature (Ta) = 22.0(0.8)degrees C; mean(s.d.) relative humidity (rh) = 67(6)%) and the subsequent three trials were carried out at weekly intervals in the heat (mean(s.d.) Ta = 34.6(0.6)degrees C; mean(s.d.) rh = 60(7)%). There were no significant differences between trials in the heat for heart rate, rectal temperature, skin temperature or VO2 (repeated measures analysis of variance), and total sweat loss (one-way analysis of variance). As changes in these variables are seen with heat acclimation it was concluded that there was no heat acclimation effect and separating exercise bouts by 1 week was a valid method for comparing the effects of different treatments on unacclimatized males during exercise in the heat.
Acclimatization↗
Antiphospholipid syndrome in scleroderma.
Scleroderma has not been described in association with the antiphospholipid syndrome (APS). Only a single manifestation, that of large vessel arterial thrombosis, has been noted in patients with scleroderma and antiphospholipid antibodies. We describe the first case report of a patient with scleroderma and a "full house" for the APS. Clinical suspicion, appropriate investigation and early treatment may help limit the progression of the vasculopathy seen with this syndrome.
Adult↗
In vivo binding to dopamine receptors: a correlate of potential antipsychotic activity.
Antagonists of dopamine receptors (especially those of the D2 subtype) have long been recognized as effective antipsychotics. SCH 39166, a dopamine D1 selective antagonist, is now also being evaluated for its clinical antipsychotic properties. The studies described herein determine the binding affinity of a variety of dopamine receptor antagonists (both dopamine D1 and D2 selective compounds) for the dopamine D1 and D2 receptors, in vivo, and correlate this affinity with their behavioral activity in the rat conditioned avoidance response (CAR) test. The in vivo binding affinities of the D1 selective compounds at the dopamine D1 site exhibited a high correlation (r = 0.97) with their activities in the rat CAR test. Likewise, D2 selective compounds' inhibition of in vivo binding to dopamine D2 receptors correlated with their behavioral potencies (r = 0.98). Conversely, any binding of selective agents to their non-targeted receptor did not correlate with their behavioral activity. These data suggest that in vivo binding to either dopamine D1 and/or D2 receptors is predictive of potential antipsychotic efficacy.
Animals↗
Safety of fluconazole in women taking oral hypoglycaemic agents.
Explore the source record for details and available documents.
Administration, Oral↗
Highlights of D1 dopamine receptor antagonist research.
SCH 39166 is now undergoing clinical trials in schizophrenics as a selective D1 dopamine receptor antagonist. It differs from SCH 23390, the prototype D1 receptor antagonist, by having reduced affinity for serotonin receptors and a longer duration of action in primates, as measured in the squirrel monkey conditioned avoidance paradigm. Further studies on this difference in primates indicates that it may be attributable to reduced affinity of SCH 39166 compared to SCH 23390 for the hepatic glucuronosyltransferase system. Their affinities are similar in rats, a species in which both have similar duration of action. These and other studies presented are consistent with the novel profile of SCH 39166.
Animals↗
SCH 39166, a potential antipsychotic drug, does not evoke movement disorders in cebus monkeys.
Subchronic administration of a neuroleptic in cebus monkeys can reliably mimic the abnormal movements produced by these drugs in humans. SCH 39166 is the best candidate to test in this model to determine if selective antagonism at the dopamine D1 receptor is devoid of these side effects. It has superior selectivity for the dopamine D1 site versus several other sites and a significantly longer duration in primates than the prototypical D1 antagonist, SCH 23390. In contrast to haloperidol, weekly administration of SCH 39166 for 14 weeks did not produce abnormal movements but did produce equivalent sedative effects. Thus dopamine D1 antagonists are uniquely different from D2 antagonists with regards to the production of abnormal movements.
Animals↗
Some observations in the figure drawings of clumsy children.
This paper presents two exploratory studies of figure drawing by clumsy children. In the first, the drawings of 42 such children and controls, matched pairwise on chronological age and verbal IQ, were compared. Not only were the impaired children's drawings found to be generally delayed but there was also a suggestion that some fell further behind their peers as they got older. In a follow up study of a subset of the clumsy group it was found that increasing delay was indeed characteristic of some children, but others improved. In spite of improvement in some aspects of figure representation, however, the children's poor motor control persisted.
Adolescent↗