Midwives and the maternity benefit.
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Biomedical subjects
Publications and source records attributed to A Scott.
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The excavations at Christ Church, Spitalfields (1984-86) produced a sample of 968 human skeletons which were interred between 1729 and 1859. Of these, 387 were recovered in association with coffin plates stating name, age at death, and date of death. There are 138 adult females in the named sample and the obstetric histories of 94 have been reconstructed from historical documentation. Such variables as birth spacing, number of children, and age at first and last births are known for the majority of this sample. Any individual about whose history there is any doubt has been excluded from the analysis. A middle-class group, they were largely of high nutritional status and, by the standards of the day, lived in sanitary and comfortable conditions. Both males and females have a mean age at death of 56 years. The presence or absence, the typology, the severity, the width and the length of the preauricular sulcus, the presence or absence and the number of pits on the dorsal aspect of the pubic body, sulci along the anterior sacrum adjacent to the auricular facet, and the extension of the pubic tubercle were evaluated in relation to the obstetric histories of these females. Statistical analysis has demonstrated a relationship between the presence of pubic tubercle extension and parity status and between the degree of extension and the number of children borne (P < .02). Statistically there is no significant relationship (P > .05) between either the preauricular sulcus or pubic pitting and parity status. Sacral scarring is significantly associated (P < .05) with parity status, but as it was evident in only eight females it has little practical application. Sample sizes are small, and it must be considered that statistical evaluation of larger samples might detect associations between variables not demonstrated here. There is no significant relationship between any of the cortical variants under consideration and age at death.
We have recently described the production of large amounts (< or = 65 grams per litre) of enzymatically active human alpha 1 antitrypsin in the milk of transgenic sheep (Wright et al., 1991). Here, we describe in more detail the expression of the human protein in the milk of these animals throughout the lactation period. Human alpha 1 antitrypsin is also found at much lower levels in the plasma of transgenic ewes before, during and after lactation. It is also detected in male plasma at very low levels. We have previously shown human alpha 1 antitrypsin purified from transgenic sheep milk to be indistinguishable from commercially available human plasma derived alpha 1 antitrypsin in terms of gross sugar content and in vitro activity. Here we extend this comparison to more detailed analyses of glycosylation state, amino-terminal sequence, pI value, and molecular weight determination by mass spectrometry.
All patients admitted to an Intensive Care Unit were assigned randomly to one of two groups, A and B. Group A received colloid volume replacement as 4.5% albumin whilst group B received a synthetic colloid, polygeline. This study describes the changes in serum albumin concentration in survivors and nonsurvivors in the two groups during their stay in the Intensive Care Unit. The incidences of renal failure and pulmonary oedema were also assessed. Serum albumin concentration decreased in all nonsurvivors. In survivors the serum albumin concentration decreased to a greater extent in the synthetic colloid group than in the albumin group. Despite the differences in serum albumin concentration there were no significant differences between the groups in the incidences of pulmonary oedema or renal failure.
The design and methods of this longitudinal study of dementia which is underway are described. An age- and sex-stratified random sample of 6,000 elderly community subjects are being re-assessed after a 2-year interval using the GMS-AGECAT package. Alpha forms part of the MRC funded UK multicentre incidence study and an international network of collaborative studies using comparable measures.
The GMS-AGECAT package was used in the initial assessment and 3-year follow-up of a random sample of 1,070 elderly people living in the community. A prevalence of 4.3% is found for dementia after confirmation of diagnoses by outcome at year 3. The overall incidence of dementia was 9.2/1,000 per year after partial adjustments for outcome of year 6. Incidence per year for sub-types of dementia were AD 6.3/1,000, vascular 1.9/1,000, and alcohol-related 1.0/1,000.
A group of 1070 community-living persons aged 65 and over was assessed using the GMS-AGECAT package and other interviews at years 0 and 3. Year 3 interviewers were 'blind' to the findings at year 0, and the prevalence of organic disorders and depression was very similar in both years. According to the results at year 3, minimum and maximum prevalence figures for dementia at year 0 were 2.4% and 3.8% for moderate to severe and 0.4% and 2.4% for mild or early cases, with a best estimate of 3.5% and 0.8%, or 4.3% overall, divided into: senile, Alzheimer's type 3.3%; vascular 0.7%; and alcohol-related 0.3%. The overall incidence of dementia, clinically confirmed by six-year follow-up, was 9.2/1000 per year (Alzheimer type 6.3, vascular 1.9, alcohol related 1.0). Three years later, 72.0% of those with depressive psychosis and 62.3% of those with depressive neurosis were either dead or had some kind of psychiatric illness. Nearly 60% of milder depressive cases (7.2% of the total sample) had either died or developed a chronic mental illness. The outcome of depressive pseudodementias is equivocal so far. Findings at year 3 provide validation of AGECAT computer diagnosis against outcome; organic and depression diagnoses are seen to have important implications for prognosis.
Concentrations of urinary albumin and the albumin:creatinine ratio were measured in early-morning urine specimens from 5670 people older than 40 years who participated in a health screening survey of a local workforce. Sex-specific reference intervals were determined in a subgroup of 3597 people after excluding 2073 individuals with Albustix-positive proteinuria; diabetes mellitus; bacteriuria; current hypertension; body mass index greater than or equal to 30 kg/m2; or serum triglyceride greater than or equal to 2.5 mmol/L. The 97.5 percentile concentration for urinary albumin was 28 mg/L in men and 29 mg/L in women; for the albumin:creatinine ratio this was 2.3 g/mol in men and 2.8 g/mol in women. In the study population, the degree of albuminuria showed piecewise log-linear relationships with diastolic blood pressure (P = 0.0001) and body mass index (P = 0.0001), log-linear relationships with hypertriglyceridemia (P = 0.0001) and hypercholesterolemia (P = 0.0001), and a negative piecewise linear relationship with high-density lipoprotein (HDL) cholesterol (P = 0.0461).
Although, major histocompatibility complex (MHC) class II antigen expression in allografts is thoroughly studied, regulation of the genes for these antigens is not fully understood. The graft-specific MHC class II genes are potentially important in determining the immunogenicity of graft but their detection in a mixed-cell population such as in the allograft would require unambiguous differentiation of graft-specific class II expression from those in host lymphoid cells. With an oligonucleotide probe that specifically hybridizes to I-Ab mRNA from H-2k haplotype mice, we have studied I-A gene expression in cardiac allografts heterotopically transplanted from B10.Br (H-2k) to B10.D2 (H-2d) mice. Normal B10.Br hearts do not have appreciable I-Ab transcripts as determined with this probe, but 4 days after allografting, a substantial increase in I-Abk messenger RNA (mRNA) content was noted in the allografted hearts which persisted for the next 2 days and then decreased concomitant with destruction of the heart. The increase in I-Abk mRNA preceded the expression of surface Iak antigens on dendritic and endothelial cells in the allograft. These data indicate increased transcription of the I-Ab gene in cells of graft origin suggesting that transcriptional regulation is the initial mechanism for expression of class II genes in allografts. The sustained rise in graft-specific class II mRNA also seen in these allografts suggests that increased mRNA stability may be another mechanism for the increased density of class II antigens in allografts undergoing rejection.
It has been suggested that surgery for abdominal aortic aneurysm (AAA) be confined to designated centres. A prospective audit of 200 consecutive AAA repairs at a district general hospital was performed between 1981 and 1990. The 30-day mortality rates for elective, symptomatic and ruptured aneurysm repair were 1.4%, 3.5% and 30%, respectively. The major factor affecting outcome after the mode of presentation was the age of the patient, with 30-day mortality rates for emergency treatment increasing from 21% (age range 60-69 years) to 42% (age range 70-79 years). This mortality rate for ruptured aneurysms is an underestimate, with two-thirds of patients with rupture dying before reaching hospital and some patients dying in hospital undiagnosed. The major contribution to improved overall mortality would therefore be detection before rupture (usually by ultrasound) and improved diagnostic accuracy. Many patients with ruptured aneurysms had symptoms for only a short period before presentation (42% for less than 6 h) and required urgent surgery (26% reached theatre within 1 h). These two factors make long-distance transfer of these patients an unrealistic option. The concentration of this type of surgery in relatively few centres will distance the patient from their relatives and reduce the opportunity for the majority of junior doctors to acquire an understanding of the presentation, natural history and management of aortic aneurysms. This understanding when combined with a screening programme is likely to have a far greater impact on the overall mortality from AAA than restricting the centres for surgical treatment.
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The treatment of visceral leishmaniasis (VL) may be complicated by drug toxicity or intolerance, and by drug resistance. Amphotericin B (AmB) is effective, but its use is limited by toxicity: renal impairment, anaemia, fever, malaise, and hypokalaemia are common. Liposomes have been proposed as an effective way to target drugs at macrophages, which are the cells infected in visceral leishmaniasis. In animals AmB incorporated into liposomes is highly effective against experimental leishmaniasis, with low toxicity. This report is of the successful treatment of a patient with multiply drug-resistant visceral leishmaniasis with a commercially prepared formulation of liposomal amphotericin B (L-AmB) ('AmBisome', Vestar, San Dimas, California, USA). We also report, for comparison, a patient treated with conventional AmB, and preliminary studies in mice comparing the two agents.
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Caffeine is both ingested by pregnant women in their third trimesters and administered therapeutically to premature infants to stimulate respiration. This experiment attempted to delineate any persistent effects of low dose caffeine exposure during the first week of life in rats, since this time period provides an animal model equivalent to the human third trimester or premature infant exposure. Rat pups who had received either 1 or 9 mg/kg of caffeine during the first week of life grew more slowly, were hypoactive at two weeks of age, and were impaired on an operant spatial learning task as adults. Adding visual cues to the operant task did not improve their performance. The timing of the appearance of developmental landmarks, adult body weight and adult brain weight, however, were not affected by postnatal caffeine exposure. The persistent behavioral deficits noted after postnatal caffeine exposure were all opposite in direction to the acute effects of caffeine, and similar to the effects of adenosine. Thus the behavioral deficits reported here may reflect an upregulation of developing adenosine receptors that persists into adulthood subsequent to early chronic postnatal caffeine exposure.
We describe the generation of five sheep transgenic for a fusion of the ovine beta-lactoglobulin gene promotor to the human alpha 1-antitrypsin (h alpha 1AT) genomic sequences. Four of these animals are female and one male. Analysis of the expression of h alpha 1AT in the milk of three of these females shows that all express the human protein at levels greater than 1 gram per liter. In one case initial levels exceeded 60 grams per liter and stabilized at approximately 35 grams per liter as lactation progressed. Human alpha 1AT purified from the milk of these animals appears to be fully N-glycosylated and has a biological activity indistinguishable from human plasma-derived material.
The mechanism by which isoproterenol (ISO) prevents the prolongation of action potential duration (APD) and refractory period (RP) by the class III antiarrhythmic agent E-4031 was studied. E-4031 (1 microM) increased RP by 50% with no effect on contractile force in papillary muscles isolated from guinea pig heart. ISO (1 microM) increased force of contraction more than fivefold and decreased RP by 25%. The prolongation of RP by E-4031 was prevented by pretreatment of muscles with ISO. The prolongation of APD in isolated guinea pig ventricular myocytes by 5 microM E-4031 also was antagonized by prior exposure of the cells to 1 microM ISO. Instantaneous currents and delayed rectifier K+ currents, IK, were measured in isolated myocytes using the suction microelectrode voltage-clamp technique. Currents were measured in response to 225-msec depolarizing pulses from a holding potential of -40 mV. Previous studies have demonstrated that IK in these cells results from activation of two distinct outward K+ currents, IKs and IKr (specifically blocked by E-4031). ISO doubled the magnitude of IKs without significant effect on IKr. The instantaneous current, putatively identified as a Cl- current, also was doubled by ISO but was unaffected by E-4031. The augmented conductance of IKs and instantaneous current by ISO results in a decrease in RP. The small effect of E-4031 on APD and RP in the presence of ISO results from the smaller contribution of IKr relative to the augmented repolarizing currents.