Search PubMed⌕ Search

Biomedical subjects

C Grant

Publications and source records attributed to C Grant.

At least 91 records · Page 5Linked to original sources
PubMed1995

Autosomal dominant cerebellar ataxia deafness and narcolepsy.

A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.

Adolescent↗
PubMed1995

A method for frequent measurement of sedation and analgesia in sheep using the response to a ramped electrical stimulus.

A method for the frequent, precise measurement of the analgesic and sedative (or anesthetic) effects of drugs after bolus administration to sheep was developed. A ramped pulsed DC electrical stimulus was delivered to the hind limb of sheep via subcutaneous needles by use of a peripheral nerve stimulator modified to allow control of current ramp rate and pulse frequency, and limb withdrawal was used as an endpoint. The optimal stimulus pattern was found to be a pulse frequency of 20 Hz, with a 5-sec ramp time and measurement intervals of 30 sec. The effects of a range of analgesic and sedative drugs on the threshold current to produce limb withdrawal were examined. Administration of the sedative/anesthetic drugs propofol and thiopentone intravenously and of the analgesic xylazine both intravenously and intramuscularly resulted in a reproducible dose-dependent rise in the threshold current required to produce limb withdrawal. Administration of the opioids alfentanil and pethidine produced agitation, making measurements unreliable. It is concluded that this device allows repeated reproducible measurements of analgesia and sedation to be made in sheep at a frequency sufficient to characterize the initial effects of analgesic and sedative drugs, particularly after intravenous administration.

Analgesics↗
PubMed1995

Molecular detection of a common mutation in coagulation factor V causing thrombosis via hereditary resistance to activated protein C.

More than half of all patients with familial or recurring venous thrombosis have hereditary resistance to activated protein C (HRAPC) as the result of specific missense mutation in the gene for coagulation factor V. Because the mutant factor Va (with an Arg to Gln substitution at codon 506) cannot be cleaved and inactivated by activated protein C, carriers of this mutation are at significantly increased risk of venous thrombosis. We have recently introduced a direct polymerase chain reaction (PCR)-based clinical diagnostic test for the factor V codon 506 mutation based on the destruction of an Mnl I restriction site by the causative nucleotide substitution. To assess the accuracy of this PCR-based assay, we compared a functional clotting time test for HRAPC with the direct mutation test. Of 47 patients dually tested, only five had discrepant values for the functional test versus the DNA test. Either of these two complementary assays is useful for the accurate diagnosis of HRAPC. The DNA-based test is, however, specifically recommended for evaluation of anticoagulated patients or patients with borderline functional tests and confirmation of genotype in HRAPC families. In an additional analysis of 287 normal individuals, we found an extremely high prevalence of the mutated codon 506 allele-- approximately 4% in each of two different populations. The absence of disease in the majority of heterozygous carriers suggests that symptomatic thrombosis requires the simultaneous presence of both a mutated factor V protein and additional synergistic factors.

Codon↗
PubMed1995

Heart rate variation, age, and behavior in subjects with senile dementia of Alzheimer type.

Minute-by-minute heart rate (HR) recordings over a period of 24 h were obtained once for 30 elderly subjects diagnosed as having senile dementia of Alzheimer type (SDAT). Twenty-one of the subjects were studied in a hospital ward setting, and nine were studied in their own homes. Twelve were men and 18 were women. Eleven took some form of sedative medication; 10 took no medication. Thirty-minute mean values were unmasked to take account of the effects of activity and sleep on HR. Results indicate that the masked HR circadian rhythm of SDAT may be more often unimodal than that of normal subjects of similar age, and that phase shift of the endogenous, clock-mediated component of the rhythm (with higher HR at night) is to be expected in a proportion of individuals with SDAT.

Age Factors↗
PubMed1994

DNA ploidy and the percentage of cells in S-phase as prognostic factors for women with lymph node negative breast cancer.

BACKGROUND: Previous cell kinetic studies have shown that the percentage of cells in S-phase (%S) of the tumor may be an important prognostic factor for relapse-free survival (RFS) and overall survival (OS) in patients with resected lymph node negative breast cancer. METHODS: This study examined DNA ploidy and %S from the paraffin embedded primary tumors of 265 patients who had surgery between 1975 and 1981, had lymph node negative cancer, and had no adjuvant therapy. The %S and %G2M values were calculated using a debris and aggregate subtraction model. RESULTS: The results of the DNA ploidy analysis revealed 130 (49%) DNA diploid tumors and 135 (51%) DNA nondiploid tumors. Ploidy was not significant for either RFS (P = 0.20) or OS (P = 0.13). The total %S (using a cutoff of 8%) was a statistically significant prognostic factor for RFS (P = 0.003) and borderline for OS (P = 0.08). The proliferation fraction (%S + %G2M), using a cutoff of 12.5, was a statistically significant prognostic factor for RFS (P = 0.01) and for OS (P = 0.01). In a Cox multivariate analysis for RFS, the total %S remained significant (P = 0.05) along with tumor size. In the analysis of OS, the proliferation fraction remained significant (P = 0.03) along with tumor size and age. DNA ploidy was not significant in any multivariate analysis. CONCLUSIONS: This study suggests that tumor size and cell proliferation parameters are independent prognostic factors for patients with resected lymph node negative breast cancer. However, the clinical usefulness of the cell kinetic parameters appears limited.

Adult↗
PubMed1994

Variation in coverage by ethnic group of neonatal (Guthrie) screening programme in south London.

OBJECTIVES: To determine whether coverage of the neonatal (Guthrie) screening programme in Britain is different for groups at highest risk of sickle cell disease and to identify possible reasons for incomplete coverage. DESIGN: Descriptive study of coverage of screening programme and its variation by mobility, district of residence, and ethnic group. SUBJECTS: 1727 infants born between 1 October and 31 December 1991. SETTING: Former West Lambeth and Camberwell District Health Authorities, London. MAIN OUTCOME MEASURE: Proportion of infants with an identifiable screening test result. RESULTS: Screening covered 1663/1727 (96.3%) infants overall (745/786 (94.8%) in West Lambeth; 918/941 (97.6%) in Camberwell). The relative odds ratio of an African infant not having been tested compared with a white infant was 3.05 (95% confidence interval 1.30 to 7.14) (2.08 (0.86 to 5.01) after adjustment for mobility and district of residence). For infants whose families moved into the districts after the birth compared with those born and resident in the districts the relative odds ratio of having been tested was 10.16 (4.85 to 21.29). The odds ratio of locally delivered infants in West Lambeth not having been tested compared with those in Camberwell was 2.12 (1.08 to 4.16) after adjustment for ethnic group. CONCLUSION: Coverage of the screening programme is incomplete and poorer in infants of African ethnic group than in white infants. Poorer coverage is also associated with mobility of the family around the time of birth. The findings have implications for using the neonatal programme for testing for sickle cell disease and other disorders. Arrangements for monitoring the existing screening programme are inadequate and an improved system should be established, similar to the scheme that monitors the immunisation programme.

Africa↗
PubMed1994

Risk factors for repeatedly reactive HIV-1 EIA and indeterminate western blots. A population-based case-control study.

OBJECTIVE: Causes of indeterminate results of Western blot testing (IWB) for human immunodeficiency virus (HIV) type 1 include seroconversion, HIV-2 cross-reactivity, and autoimmune disease, but most IWB results remain unexplained. This case-control study assessed risk factors for IWB results, including early HIV infection, other retroviral infection, autoantibodies, and other medical conditions. DESIGN: Prospective study to determine HIV seroconversion rate, with a case-control design to assess other risk factors for IWB. Cases (persons with one or more repeatedly reactive HIV-1 enzyme immunoassay with IWB), their current sexual partners, and controls (persons with negative enzyme immunoassay and Western blot results) were recruited from blood banks, health department and prenatal clinics, and private providers in Washington and Oregon. RESULTS: Of 244 cases enrolled, 206 were followed up for 6 months or longer, and six (3.0%; 95% confidence interval [CI], 0.7% to 5.3%) with recent HIV risk behaviors seroconverted. The Western blot banding patterns differed among groups; cases usually had p17 or p24 bands, while controls and cases' sexual partners usually had polymerase bands. Conditional logistic regression indicated that independent risk factors for IWB among male cases and controls were a tetanus booster in the past 2 years (odds ratio, 3.2; 95% CI, 1.2 to 8.6) and sexual contact with a prostitute (odds ratio, 3.0; 95% CI, 1.0 to 9.5). Independent risk factors for women were parity (odds ratio, 1.2; 95% CI, 1.02 to 1.4) and autoantibodies, either rheumatoid factor or antinuclear antibodies (odds ratio, 2.3; 95% CI, 1.03 to 5.6). No cross-reactivity was detected with HIV-2, human T-lymphotrophic virus type 1, feline immunodeficiency or feline leukemia, or bovine immunodeficiency viruses. CONCLUSIONS: Evaluation of persons with reactive HIV-1 enzyme immunoassays and IWB should include an assessment of HIV risk and other possible risk factors, such as alloimmunization (ie, parity or recent immunization) or autoantibodies (ie, antinuclear antibodies and rheumatoid factor). The relationship of IWB among men who reported sex with prostitutes is intriguing and warrants further study.

Adolescent↗
PubMed1994

An ultrasonic Doppler venous outflow method for the continuous measurement of cerebral blood flow in conscious sheep.

A pulsed ultrasonic Doppler venous outflow method was developed for the continuous measurement of global cerebral blood flow (CBF) in conscious sheep. The sheep were prepared under anesthesia with a "suture down"-style ultrasonic flow probe on the dorsal sagittal sinus placed via a trephine hole. Angiographic and dye studies showed that the dorsal sagittal sinus at the point of placement of the probe collected the majority of the blood from the cerebral hemispheres. Studies of the blood velocity profile across the sinus showed that the dimensions of the dorsal sagittal sinus changed minimally with changes in CBF in vivo. The velocity measurements were calibrated under anesthesia against an in vivo direct venous outflow method. Control CBF values for six sheep ranged from 31 to 53 ml/min for the area of brain described above; for two sheep in which the weight of the brain was determined, this gave total CBF values of approximately 34 and 30 ml min-1 100 g-1. The CBF measured varied in the expected manner with changes in the end-tidal CO2 concentration in expired breath and showed transient reductions with the barbiturate thiopentone and transient increases with the opiate alfentanil. It is concluded that the method is simple and accurate.

Alfentanil↗
PubMed1994

Doppler echocardiography and the early diagnosis of carditis in acute rheumatic fever.

BACKGROUND: The incidence of acute rheumatic fever in New Zealand remains relatively high. Reliable early diagnosis of carditis is difficult and important in management. AIM: To determine if Doppler echocardiography contributed to the early diagnosis of carditis in acute rheumatic fever. METHODS: Forty-seven patients admitted to hospital with suspected acute rheumatic fever and 19 control patients, with a febrile illness due to a documented non-cardiac bacterial infection, were assessed two days and two weeks following admission. Presence or absence of clinical carditis was determined by a cardiologist unaware of the suspected diagnosis, from clinical examination, chest radiograph, electrocardiogram (ECG) and two dimensional echocardiogram. Doppler echocardiography was then performed and interpreted by a second cardiologist unaware of the diagnosis. After completion of the study the Jones criteria were applied, to categorise the patients with suspected acute rheumatic fever into four groups for the final diagnosis: no acute rheumatic fever, possible acute rheumatic fever, definite acute rheumatic fever without carditis, and definite acute rheumatic fever with carditis. RESULTS: In 19 patients with a final diagnosis of acute rheumatic fever and carditis at the baseline assessment carditis was detected by clinical assessment in 15 patients, compared with 19 patients with evidence of significant valve regurgitation by Doppler echocardiography. Following the two week assessment, all 19 patients had both clinical and Doppler evidence of carditis. Five patients with a final clinical diagnosis of possible acute rheumatic fever or definite acute rheumatic fever without carditis, had a Doppler abnormality detected. There was no clinical or Doppler abnormality in the febrile controls. CONCLUSIONS: Doppler echocardiography is more sensitive than clinical assessment in the detection of carditis in acute rheumatic fever, and can contribute to earlier diagnosis.

Acute Disease↗
PubMed1994

Comparative evaluation of alternative methods for broth dilution susceptibility testing of fluconazole against Candida albicans.

A comparative evaluation of methods for broth macro- and microdilution susceptibility testing of fluconazole was conducted with 119 clinical isolates of Candida albicans. Macro- and microdilution testing were performed according to National Committee for Clinical Laboratory Standards recommendations. For reference macrodilution testing, an 80% inhibition endpoint (MIC 80%) was determined after 48 h of incubation in accordance with National Committee for Clinical Laboratory Standards proposed standard M27-P. Microdilution endpoints were scored as the first tube or well in which a prominent reduction in turbidity (score 2 out of a possible 4) was observed compared with the growth control (Micro MIC-2). Alternative endpoint criteria were assessed independently of the reference MIC 80% and Micro MIC-2 values and included a colorimetric microdilution endpoint determined by using an oxidation-reduction indicator (Alamar Blue; Alamar Bio-sciences Inc., Sacramento, Calif.). The MICs for the two microdilution test systems were read after 24 and 48 h of incubation. The percentage of fluconazole MICs within 2 doubling dilutions of the macrodilution reference values was 94% for both microdilution tests read at 24 h. Agreement was slightly lower at 48 h and ranged from 91 to 93%. Comparison of Micro MIC-2 and colorimetric microdilution MICs resulted in agreements of 97 and 93% at 24 and 48 h, respectively. These results show excellent agreement among alternative methods for fluconazole susceptibility testing.

Candida albicans↗
PubMed1994

Multisite reproducibility of colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates.

MICs of fluconazole and amphotericin B were determined independently for 100 coded yeast isolates by each of six laboratories to determine reproducibility of results by using a colorimetric oxidation-reduction-based broth microdilution test. In addition, each site tested five quality control isolates on at least four different occasions during the study. Results agreed within a three-dilution range (mode +/- 1 log2 dilution) for 96.2% of fluconazole tests and 92.7% of amphotericin B tests. Agreement among tests with the quality control isolates was 99.4% with fluconazole and 98.6% with amphotericin B. These results indicate that the colorimetric microdilution method is reproducible among laboratories.

Amphotericin B↗
PubMed1994

Managers, myths and misses: target efficiency and health care management education in Australia.

The Australian penchant for monitoring overseas developments in general and health matters is noted. The face validity of the findings of the International Project on Culture and Management (IPCM) is assessed positively and certain structural commonalities of the health systems of the USA and Australia are identified, without attributing causality in the development of managers' attributes. Linkages between Australia, Malaysia and Hong Kong are also explored briefly. In addition, key attributes of the sample of Australian managers are discussed together with the limitations related to emerging forms of provision and organization in health services and to their distribution in the study sample. The IPCM findings may be used in course design but are unlikely to cause any major change, although one may debate on the values of applicants towards health service management education courses. The findings may help to stimulate the establishment of performance measures for management education in Australia.

Administrative Personnel↗
PubMed1993

Effect of short- and long-term experimental hyperthyroidism on plasma glucose level and insulin secretion during an intravenous glucose load and on insulin binding, insulin receptor kinase activity, and insulin action in adipose tissue.

Glucose disposal, insulin secretion, and insulin action in adipose tissue were measured in rats treated for 10 or 30 days with high doses of thyroxine (T4). Acutely induced hyperthyroidism produced a high rate of glucose disposal after an intravenous glucose tolerance test (IVGTT), accompanied by a high glucose-stimulated insulin secretion. In addition, in these rats the following phenomena were observed: (1) high insulin binding to isolated adipocytes due to an increase in the insulin receptor number; (2) high insulin binding to partially purified fat insulin receptors; (3) normal tyrosine kinase activity of fat insulin receptors; and (4) high insulin action in isolated adipocytes, such as glucose transport and lipogenesis. Chronically induced hyperthyroidism produced high rates of glucose disposal after an IVGTT, accompanied by an increase of basal and glucose-stimulated insulin secretion. These rats showed (1) normal insulin binding to either isolated adipocytes or partially purified insulin receptors; (2) normal tyrosine kinase activity of fat insulin receptors; (3) normal insulin action in isolated adipocytes. In conclusion, exogenous hyperthyroidism induced an increase in glucose disposal, probably due in part to high insulin secretion. In short-term T4-treated rats an additional increase of insulin action in adipocytes was also observed.

Adipose Tissue↗
PubMed1993

Presentation of a circulating self protein (C5) to MHC class II restricted T cells.

Presentation of a soluble self antigen, the fifth component of complement (C5), is discussed with emphasis on the differential ability of presentation by subpopulations of APC (dendritic cells, macrophages, B cells, fibroblasts, B cell lines and bone marrow macrophages). Constitutive presentation of C5 in C5 sufficient mice is a prerequisite for tolerance induction in MHC class II restricted T cells and can be directly demonstrated by the ability of ex-vivo APC from C5 sufficient, but not C5 deficient mice, to activate C5 specific T cells in vitro in the absence of added antigen. C5 presentation and tolerance induction in MHC class II restricted T cells is strictly dependent on an exogenous source of self antigen. C5 biosynthesized, but not secreted by macrophages is ignored by MHC class II restricted cells and induces neither tolerance nor autoimmunity. C5 presentation for tolerance induction depends largely on the efficiency of antigen uptake by APC, a property which varies within different APC subpopulations and with the nature of the antigen.

Animals↗
PubMed1992

Parathyroid autotransplantation.

Although rare following initial cervical exploration, reoperative parathyroid surgery may cause permanent hypoparathyroidism in 15% to 30% of patients. Immediate fresh or delayed cryopreserved parathyroid autotransplantation is the principal surgical option to resolve this complication. Between 1980 and 1990, 18 and 12 patients underwent immediate and cryopreserved autotransplantation, respectively. With a mean follow-up of nearly 5 years, 61% of the immediate and 42% of the cryopreserved tissue showed evidence of function. However, only 10 (55%) and two (17%) of the respective patients had completely discontinued treatment with calcium supplementation. Graft-dependent hypercalcemia can occur with either technique. We conclude that until cryopreserved tissue can be transplanted with more reliable success and if the excised abnormal parathyroid likely represents the only remaining gland, we would advise immediate autotransplantation. In the reoperative setting, unless a residual normal parathyroid gland is confirmed, a portion of the excised parathyroid tissue should be cryopreserved for possible autotransplantation in case hypoparathyroidism develops subsequently.

Cryopreservation↗
PubMed1992

Microbiology of postoperative wound infection: a prospective study of 1770 wounds.

A prospective study of postoperative wound infection was carried out over a 12-month period. Intra-operative swabs from the patients' anterior nares, the opened viscus and parietes were cultured using standard bacteriological techniques. Of the 1770 wounds studied, 167 (9.4%) became infected. Wound infection rates, according to clinical wound types, were clean 5.9%, clean-contaminated 10.7%, contaminated 24.3% and dirty 52.9%. The figures according to microbiological wound types were clean 4.7%, and potentially, lightly and heavily contaminated 15.3%, 22.1% and 30.2% respectively. The commonest causative organisms were Staphylococcus aureus 23.7%, Escherichia coli 16.9%, Staphylococcus epidermidis 13.5% and Pseudomonas aeruginosa 13.0%. When isolated intra-operatively, Enterobacter spp., Proteus spp., Klebsiella spp. and P. aeruginosa appeared to have a high probability of causing postoperative wound infection, but the intra-operative isolation of Bacteroides sp. was a poor predictor of subsequent wound infection.

Adolescent↗
PubMed1992

The relative effects of hypoxic hypoxia and carbon monoxide on brain function in rabbits.

New Zealand white rabbits were exposed to control conditions (n = 11), or to either a progressive hypoxic hypoxia produced by dilution of oxygen (O2) with nitrogen (n = 10) or a 1% carbon monoxide (CO) admixture for 15 min (n = 11). Both exposures caused a significant increase in cerebral blood flow (CBF) of up to 300% such that O2 delivery to the brain was unchanged. In the hypoxia group, a cortical somatosensory evoked response (CSER) was unaffected until the arterial O2 tension was below 20 mmHg. At this time, the rabbits became hypotensive, O2 delivery to the brain decreased dramatically and the CSER could not be elicited. In contrast, despite the maintenance of O2 delivery to the brain during and after the CO exposure, the CSER voltages were halved during the exposure and only recovered to about 80% of baseline subsequently. We conclude that the primary toxicity of CO to the brain in rabbits is not due to a reduction in O2 delivery.

Animals↗