Embolism interruptus.
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Biomedical subjects
Publications and source records attributed to G Lancaster.
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To measure the accuracy of incidence rates for invasive cervical cancer derived from cancer registration data, a review of histopathology records was undertaken for all cases of invasive cervical cancer, a 20 per cent random sample of CIN 3 registrations and all cases of cancer of the uterus not otherwise specified (NOS) from Greater Manchester, which were registered by the North Western Regional Cancer Registry between 1988 and 1989. The subjects were 386 cases of invasive cervical cancer, 313 CIN 3 registrations and 69 cases of cancer of the uterus NOS. The main outcome measure was the incidence rate of invasive cervical cancer in Greater Manchester after adjusting for errors in cancer registration. It was found that 375 (97 per cent) of the 386 cases of invasive cervical cancer were verified against the original pathology report but 11 cases (3 per cent) had been registered as invasive cervical cancer in error. Nine cases of invasive cervical cancer were found to have been misclassified as CIN 3, and 10 cases as cancer of the uterus NOS. As the CIN 3 cases were a 20 per cent random sample of all CIN 3 registrations, the best estimate of the number of cases of invasive cervical cancer misclassified as CIN 3 is 45, which makes a total under-registration of 55 cases over the two-year period. After adjusting for under-and over-registration, the incidence rate of invasive cancer of the cervix in Greater Manchester for 1988-1989 increased from 16.5 to 18.1 per 100,000 population.(ABSTRACT TRUNCATED AT 250 WORDS)
During 1987 a system for the computer-aided diagnosis of abdominal pain was introduced on a trial basis in seven district health authorities in the North Western (NW) Region. Despite good reports of the system from other areas, by the end of a 12-month period only two of the seven districts continued to use it in the routine management of patients. A study was undertaken to determine the difficulties that had been encountered and the way in which these had hindered successful implementation of the system. Information was obtained by interview with key personnel involved in the trial, which included the chief executive in each district, a consultant designated as responsible for the system and clerical staff. The study identified three main factors undermining the implementation of the system: a lack of consultant support; the negative attitude of junior doctors; and inadequate clerical support.
OBJECTIVE: The aim was to determine what effect the offer of a cervical smear test when attending for breast screening has on the uptake of cervical and breast screening. DESIGN: The study involved randomisation to compare uptake in those women invited for cervical screening in advance with their breast screening invitation (group 1) with those invited for breast screening only and then offered a smear test upon arrival for breast screening (group 2). The main outcome measure was improvement in the uptake of cervical screening among older women without detriment to the breast screening service. SETTING: The study took place at the Northern Hospital in North Manchester. PARTICIPANTS: Participants were 2131 women aged 50-64 years invited for breast screening at the Northern Hospital in the summer of 1990. MAIN RESULTS: Overall, 54% of the women who were eligible attended for breast screening, 52% attended from group 1 and 55% from group 2. Of those attending for breast screening, 957 were eligible for cervical screening and 193 (20%) had a smear test. There was a difference in the proportion tested from each group (p < 0.001), 28% had a smear test from group 1 and 13% from group 2. Forty five percent of the 193 had not had a cervical smear for at least five years. CONCLUSIONS: The cervical screening facility did attract some women who were overdue for a smear test and who might not normally have attended for cervical screening, and there was no evidence to suggest that it had a detrimental effect on the breast screening uptake. An advanced cervical screening invitation seemed preferable to an invitation upon arrival at the breast screening unit.
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A small-for-gestational-age female infant born at term developed severe lactic acidosis and died on day 13 of life. Two previous sibs had also died of overwhelming lactic acidosis in the neonatal period. The lactate-to-pyruvate and 3-hydroxybutyrate-to-acetoacetate ratios were elevated at 136 and 42 to one, respectively. The activities of the pyruvate dehydrogenase complex and pyruvate carboxylase in cultured skin fibroblasts were normal but a defect in respiration was indicated by the low rates of conversion of 1-[14C]pyruvate, glutamate, and lactate to 14CO2 in these cells. Skin fibroblast cultures also displayed an elevated lactate-to-pyruvate ratio (72:1) when incubated with glucose as substrate compared to control cell cultures (20:1). When mitochondrial preparations of skin fibroblasts (prepared by digitonin extraction) were tested for their ability to synthesize ATP from a variety of substrates, it was found that those of the patient made adequate amounts of ATP with either succinate or ascorbate/tetramethyl-phenylenediamine as substrate but not with the NAD-linked substrates pyruvate, isocitrate, and palmitoyl carnitine. We propose that this is indicative of a defect in the respiratory chain between NADH and coenzyme Q, for the first time demonstrable in cultured skin fibroblasts.
Mitochondrial 4-aminobutyrate aminotransferase in rat kidney can utilize pyruvate as the acceptor for the amino group of 4-aminobutyrate. Renal 4-aminobutyrate aminotransferase activity at saturating equimolar concentration of 4-aminobutyrate and 5 mM pyruvate is 42.8 +/- 2.5 mumol/g protein per h (mean +/- S.E.M.) or 70% of 4-aminobutyrate aminotransferase activity with equimolar alpha-ketoglutarate. 4-Aminobutyrate aminotransferase in brain does not transaminate with pyruvate. Since pyruvate is an important mitochondrial metabolite in kidney, net disposal of glutamate via the 4-aminobutyrate pathway is possible. The renal 4-aminobutyrate pathway in the rat has other distinctive features when compared with the pathway in rat brain. Most inhibitors of rat neuronal glutamate decarboxylase were ineffective against the renal form of the enzyme, but 20 mM semicarbazide inhibited the latter form by 80% (P < 0.001) in vitro and reduced renal 4-aminobutyrate content by 75% (P < 0.001) in vivo. In the presence of 20 mM semicarbazide, ammoniagenesis by rat renal cortex slices incubated in 1 mM glutamine was inhibited 26% (P < 0.01). Semicarbazide was proportionately less effective (15% inhibition) when ammonia-genesis was stimulated (+243%) in slices prepared from chronically acidotic animals, and was no deterrant to ammoniagenesis when non-acidotic slices were incubated in supraphysiologic concentrations of 10 mM glutamine. We conclude that whereas integrity of the renal 4-aminobutyrate pathway may contribute to glutamate disposal and thus ammoniagenesis under physiologic conditions, the pathway is a passive participant in the overall process of ammoniagenesis.
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We have examined control subjects and patients in an effor to discover a metabolic basis for dominantly inherited osterogenesis imperfecta (OI). Studies were carried out in vitro with cultured skin fibroblasts obtained from OI patients, and in vivo on peptide-bound hydroxyproline excretion in urine. Urinary hydroxyproline excretion (milligrams/24 hr) adjusted for age is essentially normal in OI patients, although the mean excretion rate is below average. The latter finding is presumably a reflection of the smaller body mass of OI patients. The OI skin fibroblasts, matched for age of donor, site of biopsy, phase of growth, and generation number in culture, incorporated L-proline into hot trichloroacetic acid (TCA)-soluble protein (collagen) at normal rates. The rate of conversion of proline to hydroxyproline in the nascent polypeptides is also normal in OI. Incorporation of L-lysine was also normal in OI. These findings indicate that peptide synthesis of collagen is not impaired in OI. Rates of galactose incorporation into collagen and the extractability of collagen into normal saline or 0.2 M citric acid were all normal both in OI cells and in the culture medium recovered from the monolayer. These findings, in combination with the urinary data on hydroxyproline excretion in vivo reveal that cross-linking and export of collagen in OI is essentially normal. The elution profile after ion exchange chromatography of fibroblast collagen on carboxymethyl (CM)--Sephadex was also examined. The normal 2/1 ratio of peak 1 (largely alpha 1(1) chains) to peak 2 ) largely alpha 2 chains) was found in OI fibroblast extracts, which implies that synthesis and initial aggregation of the two types of polypeptide to yield (alpha1(1))-2 alpha 2 collagen composition is not abnormal in OI. Despite the negative biochemical findings, a consistent defect in the morphology of OI cells was identified in the log phase and the confluent phase of monolayer cultures. The finding is characterized by irregular packing of the aggregated cells and by an irregular tessellated appearance of the individual OI fibroblast. This observation reassures us that the inherited defect is expressed in vitro.
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