Frontal lobe or 'nonspecific' dementias are genetically heterogeneous.
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Biomedical subjects
Publications and source records attributed to J Hardy.
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Six horses were subjected to 3 hours of low-flow ischemia and 3 hours of reperfusion of the large colon. After induction of anesthesia, the large colon was exteriorized through a ventral midline celiotomy. Colonic blood flow was measured continuously, using Doppler ultrasonic flow probes placed on the colonic arteries supplying the dorsal and ventral colons and was allowed to stabilize for 15 to 30 minutes after instrumentation. Low-flow ischemia was induced by reducing colonic arterial blood flow to 20% of baseline (BL) flow. Colonic mucosal, seromuscular, and full-thickness blood flow were determined on a tissue-weight basis by injecting colored microspheres proximally into the colonic artery supplying the ventral colon. Reference blood samples were obtained at a known flow rate from the colonic artery and vein at a site more distal to the site of injection. Left ventral colon biopsy specimens were harvested at BL, 3 hours of ischemia, and 15 minutes of reperfusion. Blood and tissue samples were digested and filtered to collect the microspheres, and dimethylformamide was added to release the colored dyes. Dye concentration in blood and tissue samples was measured by use of spectrophotometry, and tissue-blood flow was calculated. Data were analyzed, using two-way ANOVA for repeated measures; statistical significance was set at P < 0.05. Doppler blood flow decreased to approximately 20% of BL, whereas microsphere blood flow ranged between 13.7 and 15.5% of BL at 3 hours of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have examined the apolipoprotein E (ApoE) allele distributions in Alzheimer's disease, Parkinson's disease, senile dementia of the Lewy body type and neurologically normal controls. We have confirmed the strong genetic association between the epsilon 4 allele and Alzheimer's disease, shown that there is no association between the epsilon 4 allele and Parkinson's disease and shown that senile dementia of the Lewy body type has an epsilon 4 allele distribution intermediate between Alzheimer's disease and Parkinson's disease. On this basis, we suggest that senile dementia of the Lewy body type represents the co-occurrence of two syndromes.
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We confirm that familial clustering in late onset Alzheimer's disease is associated with the zeta 4 allele of apolipoprotein E. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Together with previously published data, it is suggested that the effect of a single zeta 4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of zeta 4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age.
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A recent study has demonstrated an association of the apolipoprotein E allele epsilon 4 (APOE*4) to familial and sporadic late-onset Alzheimer's disease (AD). Also, in late-onset AD families linked to chromosome 19, the onset age decreased when the number of APOE*4 alleles increased. A similar effect of the APOE*4 genotype was observed in early-onset AD families linked to mutations in the APP gene located on chromosome 21. We assessed whether the APOE genotype had an influence on the age of onset of AD in chromosome 14 linked early-onset AD families. No significant effect of the APOE genotype on onset age could be detected.
Since the report of a double mutation at codons 670 and 671 of the amyloid precursor protein (APP) gene identified in two Swedish families with clinically diagnosed Alzheimer's disease (AD), a carrier with dementia has died. Neuropathology confirmed the clinical diagnosis of AD. Genealogical investigations have confirmed that the two families are related to common founders. Two-point linkage analysis of the mutation versus the disease in the revised pedigree now gives a lod score of 7.62.
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Current methods of genotyping an individual's apolipoprotein (ApoE) alleles involve time-consuming separations of digested fragments on high-percentage non-denaturing polyacrylamide gels. However, it is possible to separate the fragments quicker and with greater ease using agarose.
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Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose level showed a Cpmax of 163 ng/ml and a t1/2 of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.
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The successful implantation of an ICD system with hardware from three different manufacturers is described. This case exemplifies the need for compatibility of components among different manufacturers. This is most relevant at a time when rapidly changing technology and hardware availability may require a mixing, by informed practitioners, of ICD system components. The parallel to the development of the uniform IS-1 standard for bradycardia devices is made.
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The object of this study was to assess the quantity and quality of morphine prescribing in a specialist cancer hospital. An audit of prescription charts of all patients was performed using palliative care unit recommendations as the standard. The major weaknesses identified in morphine prescription were a lack of provision of breakthrough doses, the use of 'as required' (prn) oral morphine in the absence of regular oral morphine, and the lack of reference in the unit guidelines to co-prescription of aperients, antiemetics and night sedation. These deficiencies were targeted in an education programme and the survey was repeated to complete the audit cycle. Although some improvement in prescribing practice was shown, persistent problems have illustrated the need for an ongoing hospital-wide education programme.