PubMed HealthSearch

Biomedical subjects

L Watson

Publications and source records attributed to L Watson.

At least 19 recordsLinked to original sources

Breast and ovarian cancer incidence after infertility and in vitro fertilisation.

Concern has been expressed that exposure to fertility drugs might be associated with a risk of ovarian cancer. We have examined the incidence of breast and ovarian cancer in a cohort of 10,358 women referred for in-vitro fertilisation (IVF) treatment in Victoria, Australia, between 1978 and 1992. The "exposed" group (n = 5564) had had ovarian stimulation to induce multiple folliculogenesis and the "unexposed" group (n = 4794) had been referred for IVF but were untreated or had had "natural cycle" treatment without ovarian stimulation. Duration of follow-up ranged from 1 to 15 years. Cases of cancer were determined by record linkage with data from population-based cancer registries. 34 cases of invasive breast cancer and 6 of invasive ovarian cancer were observed. A comparison with the expected numbers, derived by applying age-standardised general population rates to the cohort gave standardised incidence ratios (SIR) for breast cancer of 0.89 (95% CI 0.55-1.46) in the exposed group and 0.98 (0.62-1.56) in the unexposed group, and for ovarian cancer SIRs were 1.70 (0.55-5.27) and 1.62 (0.52-5.02), respectively. Rates of all cancers were not significantly different from general population rates. The relative risk (RR) of cancer, adjusted for age and infertility type, was, in the treated group compared with the untreated group, 1.11 (95% CI 0.56-2.20) for breast cancer and 1.45 (0.28-7.55) for ovarian cancer. The risk of body of uterus cancer was increased in the exposed and unexposed groups combined (SIR 2.84 [1.18-6.81]). Women with unexplained infertility, independent of IVF exposure, had significantly increased risks of ovarian cancer (RR = 19.19 [2.23-165.0]) and body of uterus cancer (RR = 6.34 [1.06-38.0]) compared with women with known causes of infertility. This relatively short-term follow-up suggests that ovarian stimulation with IVF is not associated with an increased risk of breast cancer. Although there was no significantly increased risk of ovarian cancer after ovarian stimulation with IVF the small number of cases limits the conclusions that can be drawn. Longer-term follow-up of large cohorts of women who have been in IVF programmes will be necessary.

Adult

Octreotide reduces alcohol-induced hypotension and orthostatic symptoms in primary autonomic failure.

Symptomatic postural hypotension is a major problem in patients with primary idiopathic autonomic failure, and ingestion of small quantities of alcohol may worsen the degree of postural hypotension. The proposed mechanisms include mesenteric vasodilation and release of vasodilatory gut peptides. We measured systemic, mesenteric, other regional vascular and biochemical responses to alcohol ingestion before and after pre-treatment with the somatostatin analogue Octreotide (which inhibits the release of a wide range of gut peptides normally released in response to food ingestion) in six patients with primary autonomic failure. Octreotide effectively prevented alcohol-induced hypotension and vasodilatation of the mesenteric vascular bed, with improvement of signs and symptoms of hypotension post-alcohol. This suggests that the mechanism of alcohol-induced symptomatic hypotension in autonomic failure is at least partly mediated by release of vasodilatatory gut peptides with resultant mesenteric vasodilatation.

Aged

Growth hormone response to clonidine in central and peripheral primary autonomic failure.

Patients with primary autonomic failure may have either pure autonomic failure (PAF) or multiple system atrophy (MSA) in which there is additional neurological involvement. Distinction between PAF and MSA at an early stage is important because a wide range of complications is associated with MSA, which has a poor response to drug therapy and a less favourable prognosis. We have investigated the growth hormone (GH) releasing effects of clonidine in patients with PAF and MSA to see whether this hormonal response could serve as a neuroendocrine marker to distinguish between the groups. Age-matched normal subjects were studied as controls. Both groups of patients had severe postural hypotension due to primary sympathetic failure of presumed central origin in MSA and peripheral origin in PAF. After clonidine, plasma GH concentrations increased in controls and PAF, with no change in MSA. Changes in plasma glucose and insulin concentrations were similar in all groups. Clonidine, therefore, stimulates growth hormone release in PAF but not MSA and may serve as a neuroendocrine marker in differentiating patients with MSA and a central autonomic defect from those with PAF with a peripheral defect.

Adult

Trends in perinatal mortality and cerebral palsy in Western Australia, 1967 to 1985.

OBJECTIVE: To analyse the trends in stillbirths, neonatal deaths, and cerebral palsy in all infants born in Western Australia from 1967 to 1985. To relate these trends to changes in perinatal care, particularly in relation to avoidance of intrapartum asphyxia in term infants and the increased survival of low birthweight infants. DESIGN: Descriptive epidemiological study calculating population rates for perinatal deaths and cerebral palsy according to year of birth and birth weight. SETTING: Western Australia. SUBJECTS: All infants born after 20 weeks' gestation or weighing at least 400 g (live and stillborn). MAIN OUTCOME MEASURES: Stillbirths, neonatal deaths (from perinatal death certificates), and cerebral palsy (from a population based register). RESULTS: Overall stillbirth rates fell from 12.1/1000 total births in 1967-70 to 8.1 in 1983-5. Early neonatal mortality fell from 13.0/1000 live births to 4.4 over the same period whereas total cerebral palsy rates remained at around 2-2.5/1000 live births. Death rates fell in all birth weight categories, particularly in low birthweight infants between 1975 and 1985, the period when birthweight data were available. In contrast, cerebral palsy rates in infants under 1500 g rose significantly over this period (from 12.1 in 1968 to 64.9 in 1985). The rise was seen in all spastic categories, including severely and multiply handicapped children. CONCLUSIONS: Large increases in the use of interventions aimed at reducing birth asphyxia and handicaps had not (by 1985) resulted in lower rates of cerebral palsy. This suggests that birth asphyxia is not a major cause. The increased survival of low birthweight infants has resulted in more cerebral palsy in this group, due either to postnatal complications of immaturity or prenatal damage to the fetal brain. These findings have implications for planning perinatal care and for litigation for putative obstetric malpractice in cerebral palsy cases.

Asphyxia Neonatorum

Pulmonary function after spinal surgery for idiopathic scoliosis.

Respiratory function was assessed in 20 patients with idiopathic scoliosis undergoing spinal surgery (median age, 15 years; range, 11-34 years; median preoperative vital capacity, 67%; range, 28-109% predicted). Ten patients underwent anterior spinal surgery through a thoracotomy incision, seven of whom had posterior spinal surgery as a second-stage procedure. The other ten had posterior spinal surgery as their initial operation. Postoperatively, three patients had clinical evidence of respiratory complications. Daytime oxygen saturation was reduced throughout the first postoperative week, with no significant difference between anterior and posterior spinal surgery. Hypercapnia was unusual and generally mild. Vital capacity was reduced significantly 1 week after both anterior and posterior spinal surgery (P less than 0.05). The median vital capacity 1 week after anterior spinal surgery was 45% of preoperative values compared with 78% after posterior surgery (P less than 0.05). Inspiratory muscle strength, as assessed by sniff mouth pressure, was 56% of preoperative values 1 week after anterior spinal surgery (P less than 0.05) and 85% after posterior spinal surgery (not significant). Vital capacity, but not sniff mouth pressure, remained significantly reduced 6 weeks after surgery. Oxygen saturation should be monitored noninvasively during the first week after both anterior and posterior spinal surgery even in patients at low risk of developing respiratory complications.

Adolescent

Respiratory disease in systemic lupus erythematosus: correlation with results of laboratory tests and histological appearance of muscle biopsy specimens.

BACKGROUND: In systemic lupus erythematosus, certain laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis reflect disease activity. A study was designed to determine if such indices predict respiratory lesions, and in particular whether the presence of vasculitis in quadriceps muscle reflects respiratory muscle function. METHODS: Twenty seven 27 patients with systemic lupus erythematosus were studied, ten of whom were consecutive untreated patients and 17 having clinically active disease and being treated. They were prospectively evaluated on the basis of erythrocyte sedimentation rate, lymphocyte count, C3 degradation products, quadriceps muscle biopsy, spirometry, lung volumes, carbon monoxide transfer factor, and mouth pressure during a maximal sniff. RESULTS: Lung function test results were abnormal in 12 patients. Vital capacity was reduced in seven, carbon monoxide transfer factor capacity in five, and mouth pressure was low (< 70% predicted) in ten. Lymphocytic vasculitis was seen in the muscle biopsy specimens of ten patients. No correlation was found between laboratory tests and lung function or mouth pressure, or between the presence of lymphocytic vasculitis and mouth pressure. In untreated patients, those with lymphocytic vasculitis had lower spirometric values. CONCLUSIONS: In systemic lupus erythematosus, evidence from muscle biopsy specimens of lymphocytic vasculitis is not predictive of impaired inspiratory muscle function as measured by mouth pressure. In untreated patients there were relationships between some laboratory test results and respiratory function, but this was not the case for the whole group. In systemic lupus erythematosus, laboratory tests and evidence from muscle biopsy specimens of lymphocytic vasculitis are therefore unlikely to be helpful in the assessment of respiratory disease.

Adult

Social class, gay men and AIDS prevention.

The relationship between sexuality, gay communities and class is potentially a very large problem for AIDS prevention. Class is a historical process which interacts with sexuality in ways still little understood. The complexities of modern class structures need full acknowledgement; labour market groupings are internally divided, and cultural privilege and exclusion are important. A community survey in New South Wales of men who have sex with men shows the class selectiveness usual in such research. An exploration of correlates of labour market position, income and education finds few relationships with attachment to milieu except for involvement with gay organisations, and minor differences in broad measures of sexuality but some class differences in HIV risk-taking and some differences in exposure to information and in attitude. An exploration of several cases from a life-history study of working-class gay men shows the impact of class circumstance on the formation of sexual relationships and points to the accessibility of unlabelled homosexual activity in working-class milieux. Research on working-class education points to the importance of curriculum change in overcoming class exclusion, and is moving towards empowerment models of great relevance in AIDS education.

Acquired Immunodeficiency Syndrome

Abnormalities of the seminal tract causing infertility: diagnosis with endorectal sonography.

Endorectal sonography, developed primarily for use in the diagnosis and staging of prostatic carcinoma, should be the first imaging technique used in the evaluation of an infertile man with low semen volume in whom either a hypoplastic or obstructed seminal tract is suspected. Endorectal sonography allows visualization of the seminal vesicles, which are otherwise difficult to examine. We used endorectal sonography to evaluate six young men, five of whom were being evaluated for azoospermia and infertility. One patient had no identifiable seminal vesicle on either side. Four patients had unilateral absence of the seminal vesicles. Of these four, three had a sonographically normal-appearing seminal vesicle on the contralateral side, and the fourth had an obstructed system contralaterally. The sixth patient had a hypoplastic system on the left and an obstructed system on the right. The delineation of an obstructed or agenetic seminal vesicle and seminal tract on endorectal sonography allows decisions to be made regarding treatment and prognosis.

Adult

Affective exchanges between young autistic children and their mothers.

This study examined autistic children's social behavior, affect, and use of gaze during naturalistic interactions with their mothers. Sixteen autistic children, 30 to 70 months of age, and 16 normal children, matched on receptive language, participated. Children and their mothers were videotaped during three situations: a free-play period, a more structured period during which communicative demand was made on the child, and a face-to-face interaction. In all three situations, autistic and normal children did not differ in the frequency or duration of gaze at mother's face. In the one condition (face-to-face interaction) during which affective expressions were coded, autistic and normal children also were not found to differ significantly in the frequency or duration of smiles displayed, and neither group displayed frowns. However, autistic children were much less likely than normal children to combine their smiles with eye contact in a single act that conveyed communicative intent. Autistic and normal children were not found to differ in the percentages of smiles they displayed to social versus nonsocial events. However, when autistic children's responses to mother's smiles specifically were examined, it was found that they were much less likely to smile in response to mother's smiles than were normal children. Finally, it was found that mothers of autistic children displayed fewer smiles and were less likely to smile in response to their children's smiles, when compared with mothers of normal children. These findings suggest that the autistic child's unusual affective behavior may negatively affect the behavior of others.

Affect

Hematologic effects of recombinant murine granulocyte-macrophage colony-stimulating factor on the peripheral blood and bone marrow.

Recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was noted to support rat bone marrow colony formation in vitro. The in vivo hematologic effects of a single intravenous injection of murine GM-CSF were therefore investigated. Doses of murine GM-CSF between 0.1 and 5 micrograms/rat caused an increasing leukocytosis that did not further increase with a dose of 25 micrograms/rat. In contrast, human GM-CSF at 25 micrograms/rat did not induce any significant peripheral hematologic effects. Murine GM-CSF induced peripheral neutrophilia and monocytosis, peaking between 4 and 8 hours and subsiding to baseline by 12 hours. Neutropenia and monocytopenia, which reached a nadir at 15 minutes, preceded the leukocytosis, suggesting that GM-CSF activates these leukocytes and causes transient intravascular margination. A mild lymphopenia occurred between 2 to 8 hours. The bone marrow at 6 hours after injection of GM-CSF demonstrated a variable and slight left-shifted myeloid hyperplasia most noticeable at the level of promyelocytes and myelocytes, suggesting a myeloproliferative effect. The marrow at 6 hours also demonstrated a decrease in mature neutrophils, documenting that the marrow contributes to the increased number of circulating neutrophils. Once-daily injection of GM-CSF for 7 days induced a repetitive daily neutrophilia of the same magnitude. The marrow after 1 week of injections did not show a generalized myeloid hyperplasia, but did show an increase in eosinophils and a decrease in lymphocytes. Granulocyte-macrophage colony-stimulating factor plus granulocyte colony-stimulating factor (G-CSF) have been reported to synergize in vitro in both mouse and human bone marrow colony assays. However GM-CSF plus G-CSF in vivo, administered as either a single injection or as daily injections for 1 week, were found in the present study to induce, at most, an additive effect on circulating numbers of neutrophils. It is concluded that murine GM-CSF will be useful in the rat model to study the in vivo hematoreconstitutive effects of GM-CSF alone and in combination with other hematologic growth factors. The relatively rapid kinetics and lesser magnitude of GM-CSF-induced neutrophilia and monocytosis, as compared to G-CSF and M-CSF, respectively, and the lesser myeloproliferative effect of GM-CSF in bone marrow smears, as compared to G-CSF, might be taken to suggest that GM-CSF's natural activity is predominantly as an inflammatory rather than a myeloproliferative factor.

Animals

Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase.

A brother and sister with long-standing symptoms of postural hypotension are described. They were considerably worse in the morning, after exercise and in warm weather. In the male, erection was unaffected but ejaculation was prolonged or absent. Both had nocturia, but there were no urinary bladder, bowel or sweating abnormalities. Autonomic function tests confirmed sympathetic adrenergic failure with spared sympathetic cholinergic and intact parasympathetic function. There were no other neurological abnormalities. Noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was elevated. Urinary levels of noradrenaline and adrenaline metabolites were below detection limits, but dopamine metabolites were normal or elevated. Dopamine beta-hydroxylase activity was undetectable in the plasma. Immunohistochemical studies of perivascular cutaneous tissue confirmed normal peptidergic and tyrosine hydroxylase immunoreactivity, with absent dopamine beta-hydroxylase immunoreactivity. The findings were consistent with an enzymatic deficit in the conversion of dopamine to noradrenaline. The parents were clinically and biochemically normal. Treatment of both patients with the synthetic amino acid, d-l-threo-dihydroxyphenylserine, which contains a hydroxyl group and is converted to noradrenaline by dopa-decarboxylase, reduced symptoms and signs of postural hypotension and increased levels of plasma noradrenaline and its urinary metabolites. In the male, ejaculation became possible. Behavioural changes included a feeling of confidence and optimism, with a tendency to be argumentative. The laevo isomer also raised blood pressure and plasma noradrenaline levels. The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa.

Adult

Occupational carbamate pesticide intoxication in three farm workers. Implications and significance for occupational health in Jamaica.

The importance of occupational health practice principles in the delivery of health care to the working population is stressed by the authors' management of an incident of occupational pesticide poisoning. The clinical management of the patients involved, as well as the occupational and environmental health management of that incident, is discussed. An illustrative case report is used to describe an occurrence of carbofuran pesticide poisoning in three female farm workers in Jamaica. This report highlights the implications and significance of this incident in terms of the sensitivity of the medical profession to similar occupational health problems.

Adult

Relationship between splanchnic vasodilation and postprandial hypotension in patients with primary autonomic failure.

The haemodynamic responses to a standard liquid meal were measured in patients with autonomic failure and in normal subjects. Resting superior mesenteric artery blood flow was similar in both groups, but mean supine arterial pressure and the superior mesenteric artery vascular resistance were higher in the patients with autonomic failure than in the normal subjects. After the meal there was a rise in superior mesenteric artery blood flow and a fall in superior mesenteric artery vascular resistance in both groups. Mean arterial blood pressure fell substantially after food in the patients with autonomic failure but not in the normal subjects. The basal heart rate, stroke distance and cardiac index were higher in the patients with autonomic failure, and rose significantly after the meal only in the normal subjects. Forearm blood flow fell and the vascular resistance rose after the meal in the normal subjects but not in the patients with autonomic failure. We conclude that superior mesenteric artery blood flow rose and superior mesenteric artery vascular resistance fell after the meal in the normal subjects and in the patients with autonomic failure. However, in the normal subjects the blood pressure was maintained by factors which include a rise in the heart rate and cardiac output. The lack of such compensatory changes probably accounts for postprandial hypotension in patients with autonomic failure.

Adult

Postnatal changes in capillary density of rat sternomastoid muscle.

The changes in muscle capillarity during postnatal growth have been difficult to study using standard histochemical methods. This laboratory has proposed the use of a lectin, Griffonia simplicifolia I (GSI), as a histochemical marker that may be appropriate for developing muscle. The purpose of the study was to compare the capillary densities (capillaries per muscle fiber) determined by the GSI lectin method, alkaline phosphatase-periodic acid-Schiff (APase-PAS) staining method, and by direct counting from 1-micron plastic sections. Sternomastoid muscles from 10-day or 6-wk-old rats were used. Results from the 10-day rats showed that the GSI method and the 1-micron method gave comparable results (1.44, 1.58 capillaries per fiber), which were significantly higher than that with APase-PAS (0.56). Capillary densities in the white region of the sternomastoid from 6-wk-old rats were identical (2.80) using both the GSI and APase-PAS methods. In contrast, the GSI method yielded significantly higher capillary densities in the red region than did the APase-PAS method (4.80 vs. 3.83). These results indicate that the GSI method for visualizing capillaries is a sensitive method for visualizing capillaries in muscle during the postnatal and juvenile growth period.

Alkaline Phosphatase

Accuracy of in vivo aminoacylation requires proper balance of tRNA and aminoacyl-tRNA synthetase.

The fidelity of protein biosynthesis in any cell rests on the accuracy of aminoacylation of tRNA. The exquisite specificity of this reaction is critically dependent on the correct recognition of tRNA by aminoacyl-tRNA synthetases. It is shown here that the relative concentrations of a tRNA and its cognate aminoacyl-tRNA synthetase are normally well balanced and crucial for maintenance of accurate aminoacylation. When Escherichia coli Gln-tRNA synthetase is overproduced in vivo, it incorrectly acylates the supF amber suppressor tRNA(Tyr) with Gln. This effect is abolished when the intracellular concentration of the cognate tRNA(Gln2) is also elevate. These data indicate that the presence of aminoacyl-tRNA synthetase and the cognate tRNAs in complexed form, which requires the proper balance of the two macromolecules, is critical in maintaining the fidelity of protein biosynthesis. Thus, limits exist on the relative levels of tRNAs and aminoacyl-tRNA synthetases within a cell.

Amino Acyl-tRNA Synthetases