Misdiagnosis of schizophrenia in older, black veterans.
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Biomedical subjects
Publications and source records attributed to D Coleman.
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The definitive diagnosis of oral hairy leukoplakia (OHL) demands that Epstein-Barr virus (EBV) is demonstrated in the lesional tissue, since the histopathological features on conventional light microscopy are not pathognomonic. We have investigated the possible use of polymerase chain reaction (PCR) technology in reaching a definitive diagnosis of this lesion by its application to ten biopsy specimens with definitive diagnoses of OHL determined by in situ hybridization. EBV DNA was demonstrated by PCR in all ten OHL biopsy specimens analysed, and none of ten control specimens. Furthermore, we have investigated the role of PCR in analysis of exfoliative cytology samples collected from the lateral border of the tongue by a minimally-invasive scraping technique. EBV DNA was not only detected in all OHL lesional scrapings but also in more than one-third of healthy controls, due to viral presence in saliva at the time of sampling. In this application, the highly sensitive PCR technique has low specificity and cannot be recommended.
OBJECTIVE: To examine the survival of patients with breast cancer diagnosed in different centres and by different methods in the United Kingdom trial of early detection of breast cancer, in order to investigate the contribution of different factors to the previously observed reductions in breast cancer mortality. SETTING: A non-randomised trial of the early detection of breast cancer, in which women aged 45-64 in two districts were offered annual screening for seven years, women in a further two districts were offered education about breast self examination (BSE), and those in four districts formed a comparison group. METHODS: Patients with breast cancer are classified according to the type of centre, method of detection, and attendance for BSE education. Univariate and multivariate survival analyses are carried out, including tumour size, dissemination status, and use of adjuvant treatment as additional variables. RESULTS: In the univariate analysis, patients with breast cancer who are non-attenders for screening have a significantly worse prognosis than those in the comparison centres. Patients whose cancer is detected by mammography have the best survival rate. The inclusion of size and dissemination status in the multivariate analysis explains only about one third of the improved prognosis in these cases. There is a significant difference between prognosis in the two BSE centres. CONCLUSIONS: The use of prognostic factors as recorded in this trial to predict breast cancer mortality may be inadequate.
Programmes of education in breast self-examination with specialist clinics for self-referral were introduced in two health districts around 1980. Combining the results from the two centres showed no reduction in mortality from breast cancer over the following 10 years but the mortality was low in one of the centres whilst in the other it was higher than in four geographically separate comparison centres in which there was similar careful monitoring of breast cancer incidence and mortality. Because this was not a randomised controlled trial and lacked a uniform treatment protocol, biases may be responsible for the differences observed, but it is also possible that BSE education with annual reinforcement contributed to the breast cancer mortality reduction seen in one district. The overall conclusion however is that the value of breast self-examination remains unproven.
Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.
"This chapter compares fertility patterns and trends in Britain with those in other West European countries. Britain shares many features in common with the rest of Western Europe: fertility below the replacement level, late childbearing with births over age 30 becoming more common. Britain stands out, however, by having one of the highest birth rates in Europe and is one of the few European countries not facing population decline in the medium term. Average age at first marriage and first birth are relatively young. Britain also has one of the highest proportions (30 per cent) of births outside marriage...[with] at least a quarter of all children...likely to experience a single parent home or a reconstituted family before age 16." Some data for the rest of the United Kingdom are also discussed.
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Among 347 AIDS patients seen at St Mary's Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.
The limitations of case review as a means of identifying errors in death certificates among breast cancer patients in a non-randomised trial of screening are illustrated by the findings of this large study. Records of 928 out of 990 deaths were available for review but were very variable in quality. Definite errors were found in 1%, errors were suspected in a further 5% and uncertainty about the cause of death, despite review, was recorded for 27%. The overall bias in reporting breast cancer deaths was less than 1%. It was concluded that the certified underlying cause of death without review provides an adequate endpoint for evaluating breast cancer screening programmes in the UK.
Lysogenization of Staphylococcus aureus by the serotype F converting bacteriophage phi 13 results in loss of beta-toxin expression. Sequence analysis of the S. aureus beta-toxin gene (hlb), the attachment site (attP)-containing region of phi 13 DNA and the chromosome/bacteriophage DNA junctions of a phi 13 lysogen, revealed that the molecular mechanism of loss of beta-toxin expression was due to insertion of the phi 13 genome into the 5' end of hlb. The insertion site (attB) within hlb contained a 14 base pair core sequence in common with attP and both ends of the integrated linear prophage genome of a phi 13 lysogen. These findings indicate that integration of the phi 13 genome into hlb is site- and orientation-specific.
Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7). All regimens achieved plasma concentrations exceeding the MIC for Candida albicans (0.25 microgram/ml). In vitro timed kill assays found that the fungicidal activity and rate of kill by cilofungin above the MIC for C. albicans was concentration dependent. At the lower dosage regimens (VLoINT, LoINT, and LoCI), cilofungin followed linear plasma pharmacokinetics, whereas at higher doses (HiCI and HiINT), nonlinear kinetics consistent with a saturated elimination pathway(s) were observed. Only HiCI and HiINT produced a 10(3)- to 10(4)-fold reduction in CFU per gram in candidiasis of the brain (P less than or equal to 0.001). HiCI and HiINT also significantly reduced infection in the choroid (P less than or equal to 0.05). All regimens, except VLoInt, significantly (P less than or equal to 0.01) reduced tissue infections in lung, liver, spleen, and kidney. However, only the regimens with nonlinear saturation kinetics (HiCI and HiINT) produced a 10(6) reduction in the spleen and a > 10(5) reduction of C. albicans in the kidney and liver. A simple doubling of the dosage from LoCI to HiCI resulted in tissue concentrations that were 10 times higher and a 10(2)- to 10(4)-fold-greater antifungal effect. There was a direct correlation (r2 = 0.83) between tissue concentrations of cilofungin and antifungal activity. Thus, continuous and intermittent infusion dosage regimens that elicit nonlinear saturation plasma pharmacokinetics of cilofungin were associated with increased antifungal activity against experimental disseminated candidiasis.
"This paper considers whether biological criteria of reproductive success are useful in considering the causes and consequences of...human population growth. Particular attention is given to the relative rates of growth of different human groups. The paper considers mechanisms of human population regulation, their classification as 'demographic regimes', and the relative importance of 'positive' and 'preventive' checks. It concludes that while in general rapid population growth now usually confers disadvantages in terms of human welfare, more traditional interpretations may still be appropriate in view of, for example, the increasing political and social influence enjoyed by rapidly increasing minorities compared with other populations in the same society which have lower rates of reproduction."
Intact mRNA has been isolated from the thermophilic fungus Talaromyces emersonii following growth on lactose-containing media and this has been used as template to produce cDNA. This cDNA has been cloned into the Escherichia coli expression system, pUC18 and this DNA was used to transform E. coli. A 2.1 kb fragment was isolated and shown to encode functional beta-glucosidase activity in E. coli. When the fragment was sub-cloned into a leaky strain of E. coli K-12, beta-glucosidase activity was detected in culture supernatants. The fragment was characterised further using restriction enzyme analysis and was also used as a probe in Northern and Southern blotting analyses of T. emersonii mRNA and genomic DNA, respectively. Results obtained from these analyses verified that the cloned insert DNA was of T. emersonii origin.
Fine catheter aspiration cytology of the peritoneal cavity was performed successfully in 61 patients admitted with acute abdominal pain. Aspirates were examined microscopically and the percentage of neutrophils in the specimen counted. In patients in whom the clinical need for operation was certain (n = 25) all patients required surgery and the peritoneal neutrophil count was greater than 50 per cent. In patients in whom the clinical need for operation was uncertain (n = 36) 19 patients required operation: the peritoneal neutrophil count was greater than 50 per cent in 18 and in one patient with ectopic pregnancy fresh blood was aspirated. Of the 17 patients not requiring operation the peritoneal neutrophil count was less than 10 per cent in 15 and greater than 50 per cent in two patients (both had acute pelvic inflammatory disease). This study confirms peritoneal cytology as a useful adjunct to decision making in those patients with acute abdominal pain in whom the decision to operate is in doubt.