On the estimation of absorption of subcutaneous injected insulin from plasma concentrations using mathematical models.
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Biomedical subjects
Publications and source records attributed to F Mollo.
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The lung concentration of coated and uncoated mineral fibres of more than 10 micron in length was determined by light microscopy in 57 autopsied subjects (23 out of which professionally exposed to asbestos) with pleural plaques but no other asbestos-related diseases. Comparisons were made with 57 controls matched for sex, age and smoking habits, who did not show any asbestos-associated diseases or history of previous occupational exposure. Subjects with pleural plaques had a median concentration of coated fibres consistently greater than that observed in those without. However, no substantial differences were found between the two studied groups when uncoated and total fibres were considered. The present study suggests that the factors related to the fibre coating and to the pleural plaque formation may be indirectly connected, but not necessarily restricted to the number and nature of the fibres, or to the professional or environmental conditions of exposure.
Splanchnic arteriovenous differences for several intermediary metabolites of carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in seven normal subjects, eight patients with cirrhosis, and six patients with cirrhosis after surgical portosystemic shunt ( SPSS ) after an overnight fast. Arteriovenous differences in the legs were also determined together with flux measurement. The individual turnover rates of acetoacetate (AcAc) and 3 hydroxybutyrate (beta OHB) were also determined by means of isotopic techniques. Splanchnic gluconeogenic precursors and FFA uptakes were lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.05 and P less than 0.01, respectively). Splanchnic triglyceride output was also lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.01), whereas no significant differences were found for AcAc, beta OHB, and glucose release. In the group of cirrhotic patients without SPSS , those patients with negligible signs of portal systemic shunt and normal splanchnic blood flow had uptake of gluconeogenic precursors and of FFA normal or higher than that of normal subjects, whereas those patients with signs of spontaneous portal systemic shunt behaved like cirrhotic patients with SPSS . Alanine release from the leg was lower in both cirrhotic patient groups. Tracer determined hepatic output of AcAc and beta OHB was higher in cirrhotic patients with SPSS (P less than 0.05). Plasma clearance rates of AcAc and beta OHB were significantly elevated in both cirrhotic patient groups. Close agreement was found between tracer and catheterization techniques in the evaluation of ketone body production in cirrhotic patients with SPSS , whereas in cirrhotic patients without SPSS tracer determined hepatic output was slightly lower, possibly because of extrahepatic splanchnic tissue ketone body uptake. In conclusion, our data in patients with cirrhosis indicate that: 1) splanchnic uptake of gluconeogenic precursors and of FFA was related to the degree of portal systemic shunt, e.g. to the degree of effective hepatic blood flow; 2) liver triglyceride but not ketone body output was decreased by the impaired FFA (and glycerol) liver uptake; 3) the higher circulating levels of gluconeogenic precursors (except alanine) and of FFA appeared at least partially due to lower hepatic removal of these metabolites; and 4) peripheral use of ketone bodies was increased and alanine release from the leg reduced in patients with cirrhosis.
An investigation was made to correlate post-mortem findings of pleural plaques (PP) with the smoking habits and occupational history of asbestos exposure of 898 adults from the general population. A significant association between PP and smoking was found in middle-aged and elderly men (p less than 0.001). When occupational history was considered, such an association was present in both exposed (p less than 0.01) and non-exposed (p less than 0.05) men aged over 50 years. No association was observed in non-exposed women, while in those exposed, the absolute number of cases was too small to evaluate any relationship. The number of cigarettes smoked did not correlate significantly with the frequency of PP. This autopsy study confirms the association between occurrence of PP and the smoking habits.
It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood. We studied five women with Cushing's syndrome with impaired oral glucose tolerance tests and seven normal subjects, plotting the shape of the insulin-induced disposal dose-response curve obtained by means of the euglycemic clamp procedure during four different plasma insulin plateaus at four infusion rates of 21, 73, 760, and 1200 mU/M2 . min. Glucose disposal (M = mg/M2 . min) was calculated as glucose amount infused to maintain euglycemia. In Cushing's syndrome the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M (337 +/- 35 vs. 657 +/- 76 P less than 0.01) during the highest insulin infusion rate [maximal glucose disposal (MGD)] without any significant difference in the levels of insulin half-maximally effective in the stimulation of glucose utilization. Neither erythrocyte nor monocyte maximum insulin receptor binding were different between the two populations. Four Cushing's syndrome patients were studied again after surgical treatment. A marked improvement of MGD was observed without any significant change in insulin-binding capacity. These results, particularly the marked decrease in MGD, a typical feature of postreceptor defects, indicate that cortisol-induced insulin resistance in man is due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step.
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Coated and uncoated mineral fibers, more than 10 micron long, were counted by light microscopy in digested lung samples from 82 adult subjects without professional exposure. Up to about 150 coated and 12,500 uncoated fibers/g dry weight were found, without any correlation to sex, occupation and smoking habit. An association between counts of more than 1,000 fibers and ages over 50 was observed. The ratio of uncoated to coated fibers was very inconstant. Only the counts of both coated and uncoated fibers seem advisable for an optical evaluation of the possibly pathological mineral fiber burden in the lungs of unexposed persons.
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Lung asbestos bodies were searched for in 65 subjects with pulmonary cancer and without occupational exposure and in 65 matched controls. No significant association between the presence of asbestos bodies and occurrence of lung cancer was found. Nevertheless, adenocarcinoma was significantly associated with the presence of lung asbestos bodies in men. The latter result suggest that, even in non-professionally exposed subjects, the possibility of relationships between asbestos exposure and lung cancer cannot be excluded.
Hyaline pleural plaques were searched for in 1,019 consecutive autopsies performed on adults in Turin. These pleural lesions were found in 173/706 males and 22/313 females (P less than 0.001). The difference between the sexes was not significant under the age of 50 years but was highly significant (P less than 0.001) in the age groups above 50 years. The severity of the pleural lesions has been graded according to the total area of the plaques. The most severe pleural abnormalities can be considered as connected with previous occupational exposure to asbestos.
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A series of 3195 necropsies performed in cases of natural death at the "S. Giovanni" Hospital in Turin, and covering the years 1969-1978, was studied for the prevalence of active tuberculosis. Active tuberculosis was found in 61 cases (1,9%); in 60 a complete clinical history was available. Forty-two out of these 60 cases (70%) were diagnosed only at autopsy, with higher frequency in the old patients. In the 42 patients with undiagnosed active tuberculosis, the acid fast bacilli resulted to have been searched for only in 3 cases, and a chest-film was recorded in 23 cases; in 27 cases of this group, the period between the admission and the death was longer than 8 days (mean 29 days). The clinical diagnosis of active tuberculosis displays intrinsic difficulties; however it must be stressed that an higher proportion of cases could be recognized if one keeps in mind the possibility of this polymorphic disease, so that adequate clinical, laboratory and x-ray investigations should carried out.
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Of 218 necropsies of male subjects, pleural hyaline plaques were detected in 67 (30%). The prevalence of pleural plaques was found to be related to age at death and to history of previous occupational contact with asbestos. The presence of asbestos bodies in lungs was also associated with pleural plaques; however, the reliability of the presence of ferruginous bodies as an indicator of exposure to asbestos is questioned. The role of environmental exposure will be better demonstrated at the end of an investigation on place of residence, which is still in progress. Chest X-rays showed little sensitivity for use in epidemiological surveys.
Thirteen liver biopsies in which the delta antigen was detected by immunofluorescence were studied by electron microscopy and immune electron microscopy with peroxidase labelled IgG and F(ab1)2 fraction obtained from a human antiserum containing high-titre anti-delta antibodies. The findings were compared with those obtained in 11 HBcAg positive and in two HBsAg negative controls. Neither unique particulate morphology nor any HB virus ultrastructural component were visualised in the delta positive specimens; 20-23 nm naked core particles were observed in 10 of 11 biopsies displaying the HBcAg in immunofluorescence. Delta positive nuclei frequently contained dense round structures of diameter varying between 20 and 30 nm with a soft indistinct edge. These granules did not exhibit characteristic ultrastructural features which enabled them to be distinguished from other granular material observed occasionally in nuclei of normal and diseased livers. However, their association with the delta antigen has been proved by the deposition on identical structures of peroxidase labelled anti-delta antibody. These results suggest that the delta antigen is unrelated to the Dane particle, the putative HB virus. The granules observed in the delta positive nuclei are composed of an amorphous matrix, possibly insoluble aggregates of the delta antigen.
Two cases of central core disease, father and daughter, of a family with dominant autosomal inheritance, are presented, one with bilateral congenital dislocation of the hip. Muscle biopsy was performed in both cases. Oxidative enzymes evidenced only type I fibers, most of them presenting a central core and not uncommonly more than one. On electron microscopy the cores generally appeared well demarcated from the surrounding fibrils and were characterized by lack of mitochondria and abnormalities of the Z line. Transitional aspects from normal fibers to completely unstructured cores were observed, as well as from well structured and unstructured cores. These findings are discussed in the light of the previous literature and particular attention is paid to the problem of differentiation between central core and multicore disease. The pathogenesis of the muscular alteration is also discussed in relation with the possibility of their neurogenic origin. Eventually, the histochemical and ultrastructural similarities between central cores and target fibers are focused.