Oestrogen replacement therapy after hysterectomy.
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Biomedical subjects
Publications and source records attributed to P Rowe.
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Irradiation fragment hybrids potentially provide highly enriched sources of region-specific human DNA. However, such hybrids often contain multiple human pieces, not all of which can be easily detected. To develop specific resources for rapidly generating markers from Xp21.3-p22.2, we have single cell cloned two previously constructed irradiation hybrids that contain markers in this region and have achieved segregation of the different known fragments originally retained. Alu-PCR products were generated from subclones positive or negative for Xp21.3-p22.2 markers, and comparison of the ethidium bromide patterns between sister subclones facilitated identification of bands likely to map to particular regions; in contrast, subclones that shared markers but were derived from independent lines showed no overlap in ethidium bromide pattern. All Alu-PCR products from one subclone, 50K-19E, in which only three closely linked markers were detected (DXS41, DXS208, DXS274) were mapped back to their region of origin. Of 28 products, 15 mapped to Xp21.2-p22.2, and these make up a new set of regionally assigned markers. However, the mapping data identified four separate Xp fragments in 50K-19E, only one of which had been picked up by marker analysis. Mapping back gel-isolated Alu-PCR products from an irradiation hybrid prior to any cloning or screening generates a comprehensive profile of the human DNA retained and permits rapid selection of sequences derived only from the region of interest.
In mice, immune responses to subunits of defined malaria antigens are regulated by genes mapping within the MHC and it has been suggested that such genetic restriction will be a major obstacle in the development of a human malaria vaccine. The relationship between class II human leukocyte antigen (HLA) genes and immune recognition of three candidate antigens for a vaccine against Plasmodium falciparum malaria has been investigated in a human population living in a malaria endemic area of West Africa. The study population was shown to be extremely heterogeneous for HLA class II alleles and marked differences in allelic frequency were detected between members of different ethnic groups. One class II DQA-DQB combination (serological specificity DQw2) was particularly common among members of the Fula ethnic group. This haplotype was significantly associated with higher than average levels of antibody to a peptide epitope, (EENV)6, of the malaria antigen Pf155/RESA. There was little evidence of association between HLA class II genotype and cellular proliferative or interferon gamma responses to the antigens tested. Overall, the number of significant associations between immune responses and specific HLA class II haplotypes was greater than would be expected by chance but less than would be expected if class II-dependent genetic restriction were a major factor governing human immune responses to malaria antigens. Thus, although some qualitative variation in the immune response to vaccine antigens may occur in ethnically different target populations, widespread HLA-associated nonresponsiveness to a multivalent subunit malaria vaccine is unlikely.
This paper describes an infant with multiple congenital anomalies who developed an unusual reaction to recurrent hospitalization before age two. After spending much of her first year in hospital, she protested strongly whenever she left the hospital. We report the evolution and treatment of this patient's misdirected attachment behaviour.
Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, greater than 90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. We demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron-exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene.
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Although evidence suggests that adolescents with chronic illness are at a greater risk for psychosocial disability, little is known about the adolescent's perception of the impact of the disease on his or her day-to-day life. Standardized measures of coping strategies, mastery, self-efficacy, social support, depression, and a semistructured interview on everyday difficulties were administered to matched groups (sex and age) of 31 adolescents with cystic fibrosis, 31 adolescents with diabetes, and 31 healthy controls. No differences were found between control and adolescents with a chronic disease responses on the standardized measures. The semistructured interview, however, revealed that the adolescent's perception of his or her physical health and the reaction of other family members to the illness were important sources of stress. These findings suggest that, in general, adolescents with a chronic illness cope effectively with their disability but that parents and clinicians must be sensitive to the adolescents' feelings and concerns regarding their health and its impact on the family.
The prevalence of variant alkaline phosphatase in the serum of 335 southern African blacks with hepatocellular carcinoma was determined using polyacrylamide gel electrophoresis. The isoenzyme was detected in 2% (seven of 335) of the patients: it could not be found in the serum of 300 matched, healthy individuals or in 56 patients with various benign hepatic diseases. Variant alkaline phosphatase is thus of little use as a diagnostic marker of hepatocellular carcinoma in southern African blacks. The reported prevalence of this isoenzyme in hepatocellular carcinoma ranges between 3% and 31%. Higher frequencies usually are recorded in populations with a low incidence of the tumor, and the lowest frequencies have been found in Chinese patients. Our finding of variant alkaline phosphatase in only 2% of another high incidence population fits this trend. Patients with tumors that secreted the variant isoenzyme had a significantly higher serum total alkaline phosphatase activity than those with tumors lacking this property.
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1. The concentrations of adrenaline and other catecholamines (noradrenaline and its major metabolite DHPG, dopamine and its major metabolite DOPAC) were measured in the hypothalamus and medulla oblongata of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) which had received a continuous subcutaneous infusion of clonidine (10 micrograms/kg per h) for 10 days, and also in WKY and SHR rats which were killed 15-18 h after the cessation of the 10-day infusion. 2. The concentrations of adrenaline in the hypothalamus and medulla oblongata/pons of the clonidine treated WKY and SHR rats were not different from their respective controls. However, the adrenaline concentrations in the hypothalamus (but not the medulla oblongata) were significantly decreased in the post-infusion WKY and SHR. 3. These results suggest that hypothalamic adrenergic mechanisms may have a common involvement in the post-clonidine infusion syndromes displayed by the WKY and SHR strains.
Motor function was assessed by use of a swim test in C57 Black mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Thirty minutes after the last MPTP injection significant motor impairment was observed while striatal dopamine was reduced to 13.9% of control levels. At 24 h and 7 days post MPTP injection dopamine levels were still reduced to 17.3% and 26.4% of control values but swimming abilities of the mice were unimpaired. Histofluorescence of catecholaminergic neurons confirmed the presence of catecholamine depletion but showed little evidence of neuronal destruction. The use of MPTP as a non-invasive means of nigrostriatal dopamine depletion in rodents and higher animals allows a re-evaluation of the role of the dopaminergic system in the modulation of movement.
Peripheral aneurysms of the leg are rare, and nearly always involve the popliteal artery. We describe the unusual presentation of a swollen leg caused by a large false aneurysm of a branch of the posterior tibial artery. This developed in the absence of either a history of trauma, local infection or infective endocarditis.
The recent discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a syndrome of Parkinsonism in man and monkey has stimulated the search for a small animal model of Parkinsonism. In this study, MPTP was administered to a series of small animals and observations made on clinical and neurochemical changes. The clinical effects of MPTP in rabbits, guinea pigs, and rats were short lived, and no chronic Parkinsonian syndrome developed. The C57 black mouse, however, although also not showing clinical changes, proved to be an ideal neurochemical model in which to study the effects of MPTP since striatal dopamine levels were reliably reduced to 13% of control values after 4 intraperitoneal injections of 30 mg/kg MPTP. Pathological study of the striatum and substantia nigra in the mouse model failed to show any alteration in neuronal morphology or numbers. Although the effect of MPTP on striatal dopamine lasted for up to 2 weeks after the last MPTP injection, the possibility exists that no neurotoxic effects occur and the observed dopamine depletion is pharmacological only.
The utility of a new glucose reflectance meter (the Reflolux; Boehringer Mannheim) and the accuracy of visually interpreted strips (Haemo-Glukotest 20-800R; Boehringer Mannheim) for the determination of blood glucose levels were assessed in a study of 50 insulin-dependent diabetics who regularly used the strips for home monitoring of their blood glucose levels. There was a highly significant correlation (r = 0,970, P less than 0,0001) between readings on the meter and results of a laboratory reference plasma glucose determination method. The patients' visual assessment of their blood glucose levels using the strips also correlated with the results of a reference method in 44 cases (88%), especially at levels below 11 mmol/l (r = 0,944, P less than 0,0001). However, readings from 6 patients were inaccurate, despite the fact that these patients regularly used the strips. A patient's ability to use the strips should be properly evaluated before it is recommended that they be used for monitoring of blood glucose levels at home. Reflectance meters are not usually necessary for satisfactory blood glucose monitoring at home. This meter may prove useful in training patients to read blood glucose assessment strips accurately, and is suitable for hospital or office use.
Sera from 391 southern African Blacks with hepatocellular carcinoma, matched controls, patients with other malignant tumours, and with various forms of hepatobiliary disease were fractionated by polyacrylamide gradient gel electrophoresis to determine the prevalence of tumour-associated gamma-glutamyl transferase isoenzymes in Black patients with hepatocellular carcinoma. One or more tumour-associated isoenzymes (I', I'' or II') were present in 58.6% of the patients with hepatocellular carcinoma: I' in 54.5%, I'' in 27.1%, and II' in 34%. These isoenzymes were detected in one patient with prostatic cancer, occasionally in patients with acute viral hepatitis, but in no normal individuals. The presence of tumour-associated isoenzymes was not related to patient age, sex or hepatitis-B virus status or to the tumour burden. Isoenzymes were present in 42 percent of hepatocellular carcinoma patients with a normal serum alpha-foetoprotein concentration and in 50% of those with a non-diagnostic value. gamma-glutamyl transferase isoenzymes may be supplementary to alpha-foetoprotein in the diagnosis of hepatocellular carcinoma.
A computer program has been prepared for grouping soil actinomycetes into cluster groups based on the presence or absence of aerial mycelium, the color of soluble pigment, and the shade of color of surface and reverse mycelium. The program automatically condenses cultures with wide ranges of characteristics into a limited number of groups and provides a permanent record so that comparisons can be made among experiments performed over a span of time. The program permits the grouping of large numbers of cultures with minimal laboratory effort and has proven useful in defining some of the ecological factors that lead to changed actinomycete populations in soils.
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A randomised double blind study of a plain T-shaped IUD and an active T-shaped IUD releasing 65 micrograms/day of progesterone, has been completed in four centres. A study of 1320 progesterone-releasing IUD's in parous women for 9660 women months of use significant to 18 months, gave a pregnancy rate of 1.0 +/- 0.4, expulsion of 4.7 +/- 0.6 and removals for pain and bleeding of 6.0 +/- 0.7. A detailed analysis of the menstrual bleeding patterns in these patients gave details of the number and length of bleeding and spotting episodes, count of bleeding days, and count of spotting episodes and days for four one-hundred-day reference periods. While the plain IUD contributed a significant number of intermenstrual spotting and bleeding days, the progesterone-releasing IUD contributed more spotting days.