Biomedical subjects
Publications and source records attributed to M Pepe.
Radioimmunological techniques were used to assay tumour markers in order to identify neoplasms in patients with thyroid nodules at the earliest possible stage. In the 7 patients with differentiated thyroid tumours, the marker findings were within normal limits. On the basis of these results it is concluded that at the present time these markers are of no value for the early diagnosis of thyroid tumours.
Two hundred and fifty-two consecutive patients with severe aplastic anaemia were conditioned by cyclophosphamide and given marrow transplants from HLA-identical siblings or parents. The results were analysed to examine the influence of marrow cell dose on graft rejection, speed of engraftment, survival and acute and chronic graft-versus-host disease (GVHD). Sixty patients received a corrected marrow cell dose below 2.2 x 10(8) nucleated cells per kg body weight, 73 patients between 2.2 and 3.2 x 10(8) cells/kg, 60 patients between 3.3 and 4.2 x 10(8) cells/kg, and 59 patients more than 4.2 x 10(8) cells/kg. The significant association between high marrow cell dose and low risk of graft rejection previously reported was confirmed. In addition, high marrow cell dose resulted in small but statistically significant reductions in time to granulocyte and platelet recoveries in patients with sustained engraftment. High marrow cell dose was also associated with a significant improvement in patient survival, a result solely due to the reduction in the incidence of graft rejection. Neither acute nor chronic GVHD were influenced by marrow cell dose. We conclude that the maximum marrow cell dose should be transplanted in patients with severe aplastic anaemia. Maximum marrow cell doses are likely to decrease the incidence of graft rejection, shorten the time to engraftment thereby decreasing the need for blood products and antibiotic support, and improve overall patient survival.
The biological effects of cosmic rays and ionising radiations on man are described. Particular attention is paid to the consequences of the environmental pollution caused by the Chernobyl accident and the relationship between I131 radiation and thyroid tumours is analysed.
The subchronic oral toxicity of 4-chloro-alpha, alpha, alpha-trifluorotoluene (CTT) was assessed in Sprague-Dawley rats. Four groups of six male and six female rats were treated daily for 28 days, by gavage, with doses of 0, 10, 100 and 1000 mg CTT/kg body weight using olive oil as a vehicle. No clinical signs were observed, other than salivation in the high-dose group in the last week. The males of this group showed a significant decrease in body-weight gain without a concurrent decrease in food consumption. In males, there were significant dose-dependent increases in blood cholesterol and triglycerides, suggestive of alterations in lipid metabolism. The females showed only a small dose-related increase in serum lactate dehydrogenase. Specific histological alterations were found in the males given 1000 mg/kg/day, namely hyaline droplet nephrosis, along with a significant increase in relative kidney weight, and an increase in lipid vacuoles in the adrenal cortex. Slight nephrosis was also observed in males given 100 mg/kg. Both male and female rats showed a significant increase in relative liver weight at a dose of 1000 mg CTT/kg. CTT appears to have a low subchronic oral toxicity. Neither pathological nor biochemical alterations were found at 10 mg/kg body weight/day and this can be defined as the no-observable-effect level (NOEL).
The case of a young woman, using a nasal spray containing corticosteroids, presenting hypertension systodiastolic, hypokalemia and hypochloremic metabolic alkalosis is presented. Clinical findings, similar to hyperfunction of the adrenal cortex, recovered quickly after discontinuation of the drug. The principal causes of hypertension associated with hypokalemia and hypochloremic metabolic alkalosis, are discussed and the importance of nasal spray, containing glucocorticoids and sympathetic agonists, as a cause of high blood pressure syndromes with different clinical expression and of difficult diagnosis is stressed. The importance of systemic absorption of drugs administered by nasal route is also emphasized.
The behaviour of the serum levels of thyroxine (T4), 3,5,3' tri-iodothyronine (T3), TSH and of the free binding sites of the thyroid hormones binding globulins in 23 patients affected by hepatic cirrhosis, is described in function of the severity of the disease. The values obtained have been statistically compared to those of a group of 14 healthy subjects. A decrease of the serum levels of T3 directly related to the severity of the disease has been remarked in the cirrhotic patients, while no significant differences in the serum levels of T4 and TSH and in the number of free binding sites on the thyroid hormones binding globulins have been noted between the two groups.
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Thirteen immuno-electrophoretically diagnosed cases of Waldenström's macroglobulinemia are presented in 11 women and 2 men aged 57-60 yr. Abdominal plain (53.34%), asthenia and weariness (46.15%), anorexia (38.46%), weight loss (38.46%), intercurrent infections (38.46%), haemorrhage (30.76%), and loss of vision (30.76%) were the most frequent symptoms. One patient presented intercostal neuritis with burning pains that only responded to cortisones. Mean survival from the date of observation was between 3.5 and 14 yr.
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An unusual case of Budd-Chiari syndrome during erythraemia is presented. Acute thrombosis of the suprahepatic veins became chronic with progressive improvement, shown clinically and radiologically in the form of partial recanalisation of thromboses of these veins and the porta. The pathogenetic relationship between polycythaemia and the Budd-Chiari syndrome is also discussed.
Behaviour of the complement system was studied in normal pregnancy, puerperium and in pre-eclampsia. CH50 showed no variations during normal pregnancy, excepting for first trimester, whereas it increased in puerperium. CVFAH50 increased steadily during all trimesters. C1q, C1s and C1-INH progressively decreased, while C3, C5, C9 and C3PA augmented. All values were clearly raised in puerperium. The decreased values of the early classical pathway components could be attributed to "blocking factors" (antibodies or immune-complexes) which could interfere with cellular immunity at fetoplacental level. The other components probably increase because there is a hormone-stimulated raised synthesis and a high turnover. The data obtained from pre-eclampsia did not reveal significant variations as compared to normal third trimester pregnancy, excepting for CVFAH50 which was reduced. This, however, does not exclude the possibility that there is an immunological pathogenesis of the pre-eclampsia, since activation of the C system is not always detectable in circulation.
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Hot-deck imputation is an intuitively simple and popular method of accommodating incomplete data. Users of the method will often use the usual multiple imputation variance estimator which is not appropriate in this case. However, no variance expression has yet been derived for this easily implemented method applied to missing covariates in regression models. The simple hot-deck method is in fact asymptotically equivalent to the mean-score method for the estimation of a regression model parameter, so that hot-deck can be understood in the context of likelihood methods. Both of these methods accommodate data where missingness may depend on the observed variables but not on the unobserved value of the incomplete covariate, that is, missing at random (MAR). The asymptotic properties of hot-deck are derived here for the case where the fully observed variables are categorical, though the incomplete covariate(s) may be continuous. Simulation studies indicate that the two methods compare well in small samples and for small numbers of imputations. Current users of hot-deck may now conduct their analysis using mean-score, which is a weighted likelihood method and can thus be implemented by a single pass through the data using any standard package which accommodates weighted regression models. Valid inference is now straightforward using the variance expression provided here. The equivalence of mean-score and hot-deck is illustrated using three clinical data sets where an important covariate is missing for a large number of study subjects.
Early diagnosis of disease has potential to reduce morbidity and mortality. Biomarkers may be useful for detecting disease at early stages before it becomes clinically apparent. Prostate-specific antigen (PSA) is one such marker for prostate cancer. This article is concerned with modeling receiver operating characteristic (ROC) curves associated with biomarkers at various times prior to the time at which the disease is detected clinically, by two methods. The first models the biomarkers statistically using mixed-effects regression models, and uses parameter estimates from these models to estimate the time-specific ROC curves. The second directly models the ROC curves as a function of time prior to diagnosis and may be implemented using software packages with binary regression or generalized linear model routines. The approaches are applied to data from 71 prostate cancer cases and 71 controls who participated in a lung cancer prevention trial. Two biomarkers for prostate cancer were considered: total serum PSA and the ratio of free to total PSA. Not surprisingly, both markers performed better as the interval between PSA measurement and clinical diagnosis decreased. Although the two markers performed similarly eight years prior to diagnosis, it appears that total PSA performed better than the ratio measure at times closer to diagnosis. The area under the ROC curve was consistently greater for total PSA than for the ratio four and two years prior to diagnosis and at the time of diagnosis.
Hallermann-Streiff-Francois Syndrome, or oculomandibulodyscephaly is a rare congenital anomaly, characterized by bilateral congenital cataracts and bird-face. As the disease always involves oral troubles, that sometimes precede or predominate over other symptoms, the patient need oral examinations and life-long rehabilitation.
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