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Biomedical subjects

T Young

Publications and source records attributed to T Young.

At least 109 records · Page 6Linked to original sources

Enhanced production of TGF-beta by blood monocytes from patients with active tuberculosis and presence of TGF-beta in tuberculous granulomatous lung lesions.

The expression of TGF-beta, a molecule that affects both immune responsiveness and wound healing, was examined in blood monocytes and granulomatous lesions from patients with active pulmonary tuberculosis. The spontaneous release of TGF-beta was higher in culture supernatants of monocytes from patients as compared with those of healthy subjects by an ELISA (p < 0.0005). TGF-beta activity was also confirmed in a bioassay in supernatants from patients. Next, freshly isolated monocytes from patients with tuberculosis and matched subjects were examined for TGF-beta activity. Cytosmears of monocytes were stained with an Ab against TGF-beta 1 (anti-LC) or isotype-specific Ab by using an alkaline-phosphatase anti-alkaline phosphatase method. In contrast to monocytes from healthy individuals, 60 to 70% of monocytes from patients demonstrated cytoplasmic staining for TGF-beta (n = 3). Upon hypotonic lysis, monocytes from patients with tuberculosis contained immunoreactive TGF-beta (n = 3). By Northern blot analysis, monocytes from three of seven patients with tuberculosis had increased expression of TGF-beta mRNA as compared with concurrently examined monocytes from healthy subjects. Within the granulomas of lung sections from two patients with untreated tuberculosis, TGF-beta immunoreactivity was identified in the Langhan's giant cells mainly and to a lesser extent the epithelioid cells using anti-LC Ab and the peroxidase-anti-peroxidase technique. Thus, both blood monocytes and lung granuloma macrophages from patients with active tuberculosis express TGF-beta. Excess activity of this cytokine in blood monocytes may underlie the depressed T cell responses of patients with tuberculosis. Moreover, within the infected tissues excess TGF-beta activity may interfere with anti-mycobacterial mechanisms and effective granuloma formation.

Gene Expression↗

The association of reproductive and menstrual characteristics and colon and rectal cancer risk in Wisconsin women.

Reproductive and menstrual characteristics were ascertained by telephone interview from Wisconsin women with newly reported diagnoses of carcinoma of the colon (n = 536) and rectum (n = 243) and 2315 population control subjects. The relationships of parity, age at first full-term pregnancy, age at menarche, regularity and length of menstrual cycles, age at menopause, and type of menopause to colon and rectal cancer were examined. In our study population, no reproductive or menstrual characteristics were significantly associated with colon cancer, although subsite analyses suggested an increased risk for transverse colon cancer in women reporting irregular menstrual cycles. Only parity was associated with rectal cancer; women who had given birth five or more times were at significantly lower risk compared to those who were nulliparous (odds ratio: 0.60; confidence interval: 0.36, 0.99). The odds ratio per birth also suggested an inverse association. These data give little support to the hypothesis that female reproductive events modify colon and rectal cancer risk.

Adult↗

MRI abnormalities in major psychiatric disorders: an exploratory comparative study.

MRI scan reports from 536 psychiatric inpatients in 10 DSM-III-R diagnostic categories and 51 normal control subjects were reviewed for incidence and severity of four types of abnormality: deep white matter hyperintensities, periventricular hyperintensities, ventricular enlargement, and cortical atrophy. Multivariate analysis revealed significant effects for both diagnosis and age and a significant interaction. After age covariance, the most discriminant type of abnormality was ventricular enlargement, with normal control subjects having significantly less enlargement than 6 of 10 patient groups, including the personality disorder and the depressed nonpsychotic groups. The data also suggested important diagnosis by age by type-of-abnormality interactions deserving of further study.

Adult↗

Hepatobiliary tuberculosis presenting as a gall bladder tumor.

A 64-year-old married female was admitted with a presentation of anorexia, easy fatiguability, skin discoloration, tea-colored urine and weight loss of 1 month's duration. After a series of clinical and laboratory examinations including radiological image studies, a diagnosis of gall bladder tumor was presumed. A final diagnosis of tuberculosis of the liver and gall bladder was established by histopathological examination of tissue specimens obtained during exploratory laparotomy. Hepatobiliary tuberculosis presenting as a gall bladder tumor is rare and no pathognomonic diagnostic characteristics can be relied upon. It is necessary to confirm the diagnosis by histopathology, polymerase chain reaction (PCR), or microbiological studies on biopsy specimens in order to make possible appropriate, early therapy.

Base Sequence↗

Oncology data management in the UK--BODMA's view. British Oncology Data Managers Association.

Over the past 10 years, the original partnership of clinician and statistician for the running of clinical research projects, especially clinical trials, has come to be supplemented by the data manager and trial coordinator. Increasing numbers of such personnel are now being employed, covering a wide diversity of work areas, including clinical research, medical audit and the cancer registries. The British Oncology Data Managers Association (BODMA) was founded in 1987 and is now in a good position to review the current status of data management in the UK. It is proposed that a national network of data managers and trial coordinators within specialist trials centres, oncology departments and district general hospitals, with a good training programme, plus a recognised career structure, is the way to make the best use of this key resource. BODMA is addressing many of these issues and aims to improve and maintain the quality of data management.

Clinical Trials as Topic↗

The occurrence of sleep-disordered breathing among middle-aged adults.

BACKGROUND: Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. METHODS: A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors. RESULTS: The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher. CONCLUSIONS: The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence.

Adult↗

Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone.

Positron emission tomography (PET) with 11C-N-methylspiperone as the radioligand was carried out in 25 chronic schizophrenic patients to determine dopamine D2 receptor density estimates in the corpus striatum. The sample included 18 neuroleptic-naive and 7 neuroleptic-free patients. Dopamine D2 receptor density estimates (Bmax) were obtained using a two-scan/four-compartment model. The Bmax estimates for the entire group (33.39 +/- 3.43 pmole/g) were significantly elevated when compared with estimates for the control group (Bmax = 15.63 +/- 2.38). The Bmax values for the entire group of schizophrenic patients showed a significant decline as a function of age. The Bmax values were significantly related to duration of illness (y = 13.2 + 10.3795x - 0.7931x2; r = 0.48). Thirteen patients and seven control subjects were added to our original publication sample (Wong et al., 1986c). The patients' Bmax values, when adjusted for age and sex effects, were significantly different compared with those of control subjects. Clinical data from the entire group were compared with published data from other research groups that have estimated dopamine D2 receptor density using different radioligands and different methods of data analysis. Comparisons of the clinical characteristics of the published studies show significant differences in patient populations, suggesting that discrepancies among published studies may reflect, in part, heterogeneity among groups of schizophrenic patients. The D2 receptor abnormality described in this study may be a late manifestation of disease, and the implications of this observation are discussed.

Adult↗

A comparison of doxorubicin, epirubicin and mitozantrone as single agents in advanced breast carcinoma.

Between July 1985 and December 1987, 87 patients with advanced breast carcinoma were randomized to receive single agent doxorubicin (70 mg/m2), epirubicin (70 mg/m2) or mitozantrone (14 mg/m2) at 3-weekly intervals. The patients had received no previous chemotherapy for their advanced disease but 91% had received prior hormonal therapy. The response rates were 36% with doxorubicin, 32% with epirubicin and 26% with mitozantrone, but these differences did not reach statistical significance. The median survival of all patients was 8.3 months. There was no significant difference in response rates or survival according to menopausal status. The toxicities of the three agents are compared. Nausea, vomiting and alopecia were more severe in patients treated with doxorubicin or epirubicin than those treated with mitozantrone. Myelosuppression and infective episodes occurred more frequently with mitozantrone. Two cardiac complications were reported. This study shows that the toxicity and low efficacy of all three agents limit their use as single agents in advanced breast carcinoma. The role of single agent chemotherapy and the relative toxicities of these drugs are discussed.

Adult↗

Elevated stimulatory and reduced inhibitory G protein alpha subunits in cerebellar cortex of patients with dominantly inherited olivopontocerebellar atrophy.

Although guanine nucleotide binding proteins (G proteins) are one of the critical components of signal transduction units for various membrane receptor-mediated responses, little information is available regarding their status in brain of patients with neurodegenerative illnesses. We measured the immunoreactivity of G protein subunits (Gs alpha, Gi alpha, Go alpha, Gq/11 alpha, and G beta) in autopsied cerebellar and cerebral cortices of 10 end-stage patients with dominantly inherited olivopontocerebellar atrophy (OPCA) who all had severe loss of Purkinje cell neurons and climbing fiber afferents in cerebellar cortex. Compared with the controls, the long-form Gs alpha (52-kDa species) immunoreactivity was significantly elevated by 52% (p < 0.01) in the cerebellar cortex of the OPCA patients, whereas the Gi1 alpha concentration was reduced by 35% (p < 0.02). No statistically significant differences were observed for Go alpha, Gi2 alpha, G beta 1, G beta 2, or Gq/11 alpha in cerebellar cortex or for any G protein subunit in the two examined cerebral cortical subdivisions (frontal and occipital). The cerebellar Gs alpha elevation could represent a compensatory response (e.g., sprouting, reactive synaptogenesis) by the remaining cerebellar neurons (granule cells?) to neuronal damage but also might contribute to the degenerative process, as suggested by the ability of Gs alpha, in some experimental preparations, to promote calcium flux. Further studies will be required to determine the actual functional consequences of the G protein changes in OPCA and whether the elevated Gs alpha is specific to OPCA cerebellum, because of its unique cellular pattern of morphological damage, or is found in brain of patients with other progressive neurodegenerative disorders.

Adult↗

Serodiagnosis of tuberculosis using the A60 IgG ELISA.

The serodiagnosis of tuberculosis (TB) by using an enzyme-linked immunosorbent assay (ELISA) to detect IgG against mycobacterial antigen 60 (A60) was evaluated. Forty-three controls (10 healthy adults, 19 patients with non-tuberculous pulmonary diseases and 14 patients with non-pulmonary infectious diseases) and 63 patients with TB in different disease activity (50 patients with active TB and 13 patients with old pulmonary TB) were studied. When a cut-off value of 200 units was selected, the results obtained with controls were: 100% negative in IgG titers in healthy adults and patients with non-pulmonary infectious diseases, 89% negative in IgG titers in patients with non-tuberculous pulmonary diseases. The overall "false positive" rate was 5% in the control groups. The percentage of serologically positive cases of active TB was: 82% in smear-positive, 67% in smear-negative/culture-positive and 38% in culture-negative. Of the 13 patients with calcified pulmonary TB, four had a positive serological response (31%). Four out of eight patients with active TB showed an elevation in IgG titer 1 to 3 months after diagnosis and anti-TB chemotherapy. The positive and negative predictive values of the test may provide valuable information according to the prevalence of TB in different populations. When the TB prevalence is high, a positive IgG ELISA test may support the diagnosis of active TB.

Antibodies, Bacterial↗

Acute renal failure associated with scrub typhus: report of a case.

We report on a 25-year-old man who had scrub typhus with the unusual complication of acute renal failure. The clinical features of fever, headache, high Weil-Felix OX-K agglutination and Rickettsia tsutsugamushi immunofluorescence titers confirmed the diagnosis of scrub typhus. Acute renal failure was proven by oliguria, urinary diagnostic indices and renal biopsy. The patient had a complete recovery after adequate medical treatment.

Acute Kidney Injury↗