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Biomedical subjects

R Harris

Publications and source records attributed to R Harris.

At least 253 records · Page 14Linked to original sources
PubMed1990

Recombination or heterogeneity: is there a second locus for adult polycystic kidney disease?

Twenty-four families with adult onset polycystic kidney disease were typed for markers flanking the PKD1 locus on chromosome 16. The aggregated results gave a significant lod score in favour of linkage to PKD1. Within this group of families two showed unusual features: recombinations, including double recombinations, and, in one family, an unexpectedly high proportion of affected people. We consider the evidence that in these families the disease might result from a mutation at a different locus, PKD2, not linked to PKD1. We suggest that a useful test is to compare the relative numbers of meioses apparently non-recombinant and doubly recombinant for markers flanking the normal disease locus, ignoring meioses recombinant for only a single marker. Using this test, neither our two families nor the data published so far on other families provide compelling evidence for the existence of a second locus for adult polycystic kidney disease. For genetic counselling in families too small to give internal evidence for or against linkage, the extra uncertainty can be handled by using a higher recombination rate.

Adolescent↗
PubMed1990

Adult polycystic kidney disease: knowledge, experience, and attitudes to prenatal diagnosis.

One hundred and ninety subjects from 100 adult polycystic kidney disease (APKD) families on the North Western Regional Genetic Register were interviewed to determine the likely demand for prenatal diagnosis. A detailed questionnaire was used to assess understanding and experience of clinical, therapeutic, and genetic aspects of APKD. Major features of the disease (presence of renal cysts which can lead to renal failure) and forms of therapy (dialysis and transplantation) were known; knowledge of less common features was related to experience. The cohort had had genetic counselling and the majority knew the risk to their own offspring, although the mechanics of the mode of inheritance was often misunderstood. Uptake of presymptomatic ultrasound testing was high, and some implications of early diagnosis are noted. A minority changed their reproductive behaviour as a result of APKD, and although the majority felt a prenatal test should be available, only 23% at high risk of passing on the disease and contemplating children felt they would be interested, and so far only one request for prenatal diagnosis has been received. Thus, demand appears to be low and to be related to perception of the seriousness of APKD.

Adolescent↗
PubMed1990

High peripheral and axial bone densities in a postmenopausal woman with untreated hypoparathyroidism.

It has been reported that bone density is increased in patients with treated hypoparathyroidism, though it is unclear whether this increase is attributable to the condition itself or to its treatment. We have recently investigated a 70 year old woman with untreated hypoparathyroidism from the time of thyroid surgery at the age of 29 years. Bone mineral content of the non-dominant distal forearm was 3.7 standard deviations above the mean normal value found in 23 healthy volunteers of comparable menopausal age, and was also above the mean normal value found in premenopausal women. The vertebral mineral density of her lumbar spine (measured by quantitative computed tomography) was 3.0 standard deviations above the mean normal value. These findings suggest that high bone density is a feature of hypoparathyroidism per se and that postmenopausal bone loss may be significantly attenuated in this condition.

Aged↗
PubMed1990

Pediatric bone marrow transplants: psychological aspects.

On a pediatric bone marrow transplant unit, hematologist-oncologists, nurses, social workers, psychiatrists, psychologists, and others on the team deal with children and adolescents whose cancers are either treatable by marrow transplantation or are ultimately fatal. Contrary to original assumptions, many children and families cope well, especially in relatively uncomplicated cases with good outcome. Treatment may include direct psychotherapeutic intervention with the child and family, as well as use of psychopharmacologic agents such as antidepressants or anxiolytics for frank psychiatric disorders. Psychotherapists often have to function adjunctively with other staff members in their interactions with the patient and the family. A stress disorder model appears to best explain child, parent and family reactions to bone marrow transplantation. Given the medical severity and complexity of the conditions treated, and the approximately equal rates of overall success and failure, a supportive consultative approach is usually most helpful for child patients, parents and staff throughout the procedure. A retrospective study of the children treated over seven years in a tertiary pediatric hospital bone marrow transplant unit is presented. The level of child, parent, and family psychopathology was usually mild to moderate, but there were clear differences between patients. Mothers were more supportive than fathers under this extreme type of stress. Prospective longitudinal studies of children and families are needed to establish causal chains and optimal therapeutic interventions.

Adaptation, Psychological↗
PubMed1990

Optic nerve involvement in viral spread in herpes simplex virus type 1 retinitis.

Colchicine was used to block fast axonal transport of the optic nerve of the uninjected eye after uniocular anterior chamber inoculation of herpes simplex virus type 1 (HSV-1). The results of these experiments suggest that second-wave virus is transported to the retina of the uninjected contralateral eye through the optic nerve of the uninjected eye, since intravitreal treatment with colchicine reduced both the viral titer and prevalence of animals with histopathologic evidence of retinitis. The chemical block to viral entry provided by colchicine was both dose- and time-dependent, with administration of colchicine that was timed to interfere with the second viral wave being the most effective. Colchicine did not appear to be directly inhibitory to viral replication or toxic to the virus, and colchicine did not cause clinical or microscopic evidence of retinal inflammation. Intravitreal injection of colchicine did not alter the timing or recovery of the first wave of virus.

Animals↗
PubMed1990

Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse.

We have demonstrated close linkage between the locus for the autosomal dominant Waardenburg syndrome type I and the placental alkaline phosphatase locus on chromosome 2q37. In five families the peak lod score was 4.76 at a recombination fraction of .023. In the mouse the Splotch locus maps to near the homologous position. Splotch mice have white spotting and hearing defects, suggesting that Splotch may be the murine homologue of Waardenburg syndrome type I.

Abnormalities, Multiple↗
PubMed1989

Uptake of presymptomatic predictive testing for Huntington's disease.

Predictive testing by means of gene probes was offered to 110 adults at risk of Huntington's disease (HD). A further 91 individuals spontaneously sought predictive testing. Acceptance rates were highest (85.1%) amongst 47 individuals who spontaneously sought testing and were referred from outside the region, and lowest (15.5%) among the 110 invited to consider predictive testing. Many expressed an interest in predictive testing, then withdrew. Fetal exclusion testing was rarely requested, and then only by individuals who lacked the necessary pedigree structure for predictive testing for themselves.

Adult↗
PubMed1989

Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes.

The human steroid 21-hydroxylase gene, CYP21B, and its closely homologous pseudogene, CYP21A, are each normally located centromeric to a complement C4 gene C4B and C4A respectively, in an organization suggesting tandem duplication of a CYP21 + C4 unit. Such an organization has been considered to facilitate gene deletion and addition events by unequal crossover between the tandem repeats. However, the large size (approximately 30 kb) of the individual CYP21 + C4 repeat units together with the difficulty in identifying reliable CYP21A- and CYP21B-specific markers has prevented direct monitoring of gene organization on individual haplotypes by conventional Southern analyses. In the present investigation we have sought to clarify the CYP21 and C4 gene organization in members of 32 British 21-hydroxylase deficiency families by employing additional experimental approaches, notably a long-range restriction mapping approach, which permits assessment through a VNTR type of analysis, of the number of CYP21 and C4 units on individual haplotypes. Our results show that there is a very high frequency (33%) of 21-hydroxylase deficiency haplotypes where functional CYP21B gene sequence has been removed as a consequence of CYP21 + C4 gene deletion while several haplotypes show evidence of gene addition. In each case that we have investigated the gene deletion and gene addition haplotypes differ in length from conventional haplotypes by integral multiples of approximately 30 kb, which strongly supports the involvement of unequal crossover mechanisms. Additionally, the comparatively frequent occurrence of CYP21 fusion genes which contain both CYP21A- and CYP21B-associated markers is suggested by the combined data from Southern analyses, long-range restriction mapping and characterization of selected regions of CYP21 genes which have been amplified in vitro.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Biochemical validation of self-reported exposure to environmental tobacco smoke.

Biochemical validation of reported exposure to environmental tobacco smoke (ETS) lends credibility to epidemiological studies investigating the association of passive inhalation of smoke to respiratory disease or lung cancer. In the current study, a series of questions regarding ETS exposure was self-administered to nonsmokers and self-reported intensity of exposure was compared with cotinine levels in urine samples obtained on site. The target population of this study was a group of municipal workers who reported exposure in a domestic setting and/or in the workplace. When asked if they were exposed to ETS on social occasions, both males and females who responded positively had higher urinary cotinine levels (P less than 0.02) than those who gave a negative response. Mean urinary cotinine concentrations were found to be elevated in both men and women who reported that they lived with a smoker. Cotinine levels in the urine of those reporting exposure were over twice as high as those in the urine of respondents who denied having been exposed. ETS exposure in the home was the greatest contributor to increased urinary cotinine levels in both men and women. Among individuals who were exposed at work only, the reported degree of exposure agreed well with the mean urinary cotinine values. Those findings emphasize that the validation of exposure status with a biomarker is an essential prerequisite for epidemiological studies investigating passive smoking.

Adult↗
PubMed1989

In-vitro and in-vivo activity of cefpirome (HR 810) against methicillin-susceptible and -resistant Staphylococcus aureus and Streptococcus faecalis.

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.

Aminoglycosides↗