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Biomedical subjects

M Abbott

Publications and source records attributed to M Abbott.

At least 37 records · Page 2Linked to original sources
PubMed1996

Oral retinoids and pregnancy.

The oral retinoids isotretinoin and etretinate are uniquely effective in the treatment of severe cystic acne and keratinisation disorders. Because of their known teratogenicity, there are strict prescription guidelines, but exposure during pregnancy still occurs. A dedicated effort by women and their clinicians is required, involving patient selection, education and informed consent, detailed contraceptive counselling, and careful monitoring and management, including pregnancy testing before commencement of therapy.

Abnormalities, Drug-Induced↗
PubMed1996

Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than-2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand malformation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus.

Cholesterol↗
PubMed1995

Prevalence of cortisol deficiency in late HIV disease.

In order to determine the prevalence of cortisol deficiency in advanced HIV disease and to examine whether it may be predicted by clinical features or biochemical abnormalities, we conducted a prospective study which assessed responses to a rapid ACTH stimulation test (short-duration synthetic corticotrophin test, synacthen test) in HIV-positive patients with a CD4 count of < or = 50 x 10(6)/l. Subjective fatigue, postural drop in blood pressure, electrolyte changes, presence of concurrent opportunist infection and drug treatment were recorded. Cortisol responses were defined as 'normal' (a post stimulation cortisol level > or = 450 nmol/l), 'abnormal' (post stimulation cortisol level < 350 nmol/l) or 'impaired' (an intermediate response). Of 49 patients tested (42 male, seven female), a suboptimal response (abnormal or impaired) was found in 14 (29%) and frank insufficiency in eight (16%). Cortisol deficiency was not predicted by postural drop in blood pressure, biochemistry or symptoms of fatigue. Patients with an impaired/abnormal test were not more likely to have cytomegalovirus or mycobacterial disease but were more likely to be taking megestrol acetate (P = 0.05, Fisher's exact test). Two of three patients with initially normal tests developed impaired/abnormal cortisol responses on re-testing 6-9 months later. Cortisol deficiency is common in late stage HIV disease, but symptoms of fatigue and postural hypotension, as well as biochemical findings, are poor predictors of cortisol deficiency. We found good subjective response to therapy. Routine screening by a rapid ACTH stimulation test is recommended in HIV-positive patients with CD4 count < or = 50 x 10(6)/l. Re-testing at regular intervals may be necessary. The interaction between megestrol acetate, cortisol metabolism and synacthen testing requires further investigation.

Adrenal Cortex↗
PubMed1995

Terminations of pregnancy for exposure to oral retinoids in South Australia, 1985-1993.

The oral retinoids, isotretinoin and etretinate, are highly teratogenic drugs which have been available in Australia since 1985 because of their unique effectiveness in severe cystic acne, psoriasis and other keratinization disorders. Only dermatologists can prescribe them, but in spite of strict guidelines by the manufacturers and the College of Dermatologists, exposed pregnancies have occurred. We attempted to determine the circumstances of exposure to these drugs for the 18 pregnancies terminated in South Australia in 1985-1993, using questionnaires to medical practitioners who notified the terminations under legislation. The main reason for their occurrence was the lack of compliance with the use of effective contraception by the women. In South Australia, some prescriptions of oral retinoids by unauthorized doctors have been dispensed during this period. Using statistics on prescriptions dispensed, an estimate was made of 1 termination of pregnancy for 319 courses of treatment for women with isotretinoin. Extension of guidelines for prescription and more detailed counselling in relation to the use of contraception are recommended. It is also suggested that doctors intending to recommend terminations obtain consent to discuss exposure with the dermatologists concerned, who may not be aware of the exposed pregnancy.

Abortion, Induced↗
PubMed1994

Pathological gamblers--will they use a new telephone hotline?

AIMS: This paper reports on the preparedness of pathological gamblers to seek help through a new national toll-free telephone hotline and compares these callers, on some key dimensions, with a representative sample of pathological gamblers living in the community. METHODS: Callers were assessed using standard diagnostic screens. Sociodemographic data and reported symptoms of stress and depression were also recorded. Callers identified as pathological gamblers were compared with their counterparts in a recent nationwide epidemiological survey. RESULTS: During the first 3 months of operation, 1506 calls were received from 329 callers. Of these 167 were pathological gamblers, 117 were partners or family members and 45 were from various agencies. Pathological gamblers contacting the hotline resembled those from the community survey with respect to gender and age. Maori and Pacific Islanders were underrepresented. Suicidal ideation was reported by over 90% of pathological gambler callers. CONCLUSIONS: The new service provides a means to reach people with serious gambling-related problems and provides information to family members and helping agencies. High reported suicidal ideation was consistent with previous studies showing elevated rates of stress and depression among pathological gamblers. Underutilization by Maori, Pacific Islanders and people with less severe gambling disorders indicates the need to find better ways to engage these groups.

Gambling↗
PubMed1993

Trinucleotide repeat length instability and age of onset in Huntington's disease.

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Adult↗
PubMed1993

A type X collagen mutation causes Schmid metaphyseal chondrodysplasia.

The expression of type X collagen is restricted to hypertrophic chondrocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the tissue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (osteochondrodysplasias). We have identified a 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score = 18.2 at theta = 0). The mutation produces a frameshift which alters the highly conserved C-terminal domain of the alpha 1(X) chain and reduces the length of the polypeptide by nine residues. This mutation may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein.

Alleles↗
PubMed1993

Reverse transcription takes place within extracellular HIV-1 virions: potential biological significance.

Extracellular HIV-1 virions purified from cell culture supernatants have been found to contain viral DNA that is the result of partial reverse transcription within the virus particles. Our data supported these observations and further indicated that the ratio of genomic RNA to viral DNA was approximately 10(3):1 for the "strong stop" (R-U5) region and 10(5):1 for the gag region. We have shown that, in the absence of detergent, large amounts of DNase-resistant viral DNA can be synthesized within intact HIV-1 virions, indicating that this phenomenon is not dependent on perturbation of the viral envelope. Nascent viral DNA synthesis also occurred in purified virions incubated at 37 degrees C in cell-free human physiological fluids including seminal plasma, blood plasma, breast milk, and fecal fluid. In vitro HIV-1 infection assays, in which HIV-1 DNA synthesis was initiated in HIV-1 virions by prior incubation with deoxyribonucleoside triphosphates, demonstrated that virus particles so treated had an increased infectious titer over untreated virions when incubated with target human T cells. Our data suggest that HIV-1 virion-associated DNA synthesis may occur in vivo and may impact on the efficiency of intra- and interhost virus transmission. If so, this phenomenon should prove to be an important target for antiviral therapeutic strategies.

Base Sequence↗
PubMed1991

Clinical profile in Barrett's esophagus: who should be screened for cancer?

A retrospective survey identified 96 patients (58 males) with Barrett's esophagus, diagnosed at the Royal Melbourne Hospital between 1978 and 1986. The age at presentation varied from 20 to 93 years, and 43% were greater than 70 years. Heartburn was a presenting symptom in 71%, regurgitation into the pharynx in 54%, dysphagia in 31% and hematemesis or melena in 29%. At endoscopy, the length of Barrett's epithelium ranged from 3 cm to 15 cm. Macroscopic esophagitis was observed in 69%, benign esophageal strictures in 14% and a co-existent adenocarcinoma of the lower esophagus in 10% of patients. Only 30% of the patients were cigarette smokers at the time of diagnosis, but 64% drank alcohol (9% greater than 80 g alcohol daily). Patients with esophageal cancer at presentation were more likely to be male and cigarette smokers (Fisher's exact probability test). It has been suggested that patients with Barrett's esophagus should be screened to detect the early development of esophageal cancer. If patients who already have cancer, the elderly (age greater than 70 years) and those with a chronic alcohol problem (greater than 80 g intake daily) are excluded from endoscopic cancer surveillance, only 42% of the patients described in this survey would be eligible for enrollment in such a program. This represents a recruitment of only 5 new patients yearly in a large teaching hospital endoscopy unit.

Adenocarcinoma↗