Biomedical subjects
Publications and source records attributed to M Monti.
We describe a form of diffuse, rapidly self-healing xanthomatosis with the clinical and ultrastructural features of hyperlipemic xanthoma but occurring in a subject with normal lipid metabolism and with no associated systemic disorders.
175 patients with Raynaud's phenomenon underwent nailfold capillaroscopy. 22 had suspected connective tissue diseases, 48 idiopathic Raynaud's disease and 105 a variety of other diagnoses. A normal capillaroscopy is fully consistent with Raynaud's disease. A pathological capillaroscopy with megacapillaries prompts suspicion of underlying connective tissue disease. The other abnormal capillaroscopies are suggestive of Raynaud's phenomenon secondary to one of the numerous associated diseases, and do not rule out evolution to connective disease ("waiting group"). The proposed simplified classification seems to offer reasonably good discrimination. The probability of an abnormal capillaroscopy increases with the age of onset of Raynaud's phenomenon but is not insignificant in younger patients. The (53-year-old) Allen's criterion (3 years follow-up without signs of underlying diseases such as scleroderma, etc.) is disappointing and should be discarded. Nailfold capillaroscopy is a non-invasive procedure which is useful at any age.
The in situ identification of lymphocyte subpopulations by means of immunopathological techniques using specific monoclonal antibodies provides a tool for the study of the gastrointestinal-associated lymphoid tissue (GALT) in health and disease. In this field, monoclonal antibodies have been applied previously using light microscopy and either immunofluorescence or immunoperoxidase; however, these techniques are not sensitive enough to allow precise evaluation of localization of labelling. We describe an immunoelectronmicroscopic method, which defines labelling specificity, since it allows the identification of cells by immunophenotype labelling and ultrastructural markers simultaneously. This in turn allows a better evaluation of the labelled cells and of the relationship between labelled and unlabelled cells. The main features of the method are the use of fresh tissue samples, fixing in paraformaldehyde CaCl2, and the coupling of the immune reaction to an amplification system (avidin-biotin-peroxidase complex). The technique yields a good preservation of cellular ultrastructure, together with a strong and specific immunolabelling. Our results confirm the high specificity of monoclonal antibodies when applied to immunopathology techniques. We confirm the pattern of distribution of various lymphocyte subsets in the jejunal mucosa described by other authors by light microscopy.
Changes in overall cellular metabolism, induced by specific inhibition of the Na-K-pump, were determined in erythrocytes from 33 normal and 25 obese subjects. Cellular metabolism was determined by measurement of heat production rates in erythrocytes suspended in plasma with and without the cardioactive glycoside, ouabain. Specific inhibition with ouabain induced the same decrease of the heat production rate in the two groups (14 +/- 5 mW/L for normal subjects and 13 +/- 5 mW/L for obese subjects). In neither group was there a correlation between the ouabain-inhibitable rate of metabolism and body weight. The present study results do not give support to the suggestion that a defect in the Na-K-pump activity would exist in the erythrocyte of human obese subjects and could not therefore be of importance in the pathogenesis of the disease.
This immunopathologic study of both normal and pathologic skin specimens (contact dermatitis [CD], lichen planus [LP], cutaneous T cells lymphoma [CTCL], and histiocytosis X [HX]) allowed as to differentiate four types of dermal OKT6+ cells: (1) cells with the same morphologic features as epidermal Langerhans cells (LCs), rarely found in either normal or pathologic dermis; (2) cells structurally similar to LCs but lacking Birbeck granules (BGs), found mainly in CD and LP; (3) larger cells rich in cytoplasmic organelles, only 5% of which contained BGs. They were especially common CTCL; and (4) cells typical of HX.
In an attempt to develop a diagnostic test for malignant hyperpyrexia (MH) without the need for open muscle biopsy, we have investigated the change in heat production brought about when platelets and muscle are exposed to halothane and caffeine. Halothane 3% caused platelet aggregation, which was itself associated with heat production. Caffeine 4 mmol litre-1 decreased heat production in platelets from both MH susceptible and non-susceptible individuals. Muscle exposed to 4% halothane showed an increase in heat production in both types of tissue. There were no significant differences in heat production between MH-susceptible and non-susceptible tissue in any of the tests.
Direct microcalorimetry was used for measurements of heat production in cell suspensions of platelets and adipocytes, obtained from hypothyroid patients before and after 3 months on full L-thyroxine substitution. Platelet heat production was significantly lower than normal before treatment and increased in all 10 patients studied; the mean value increased from 51.3 +/- 1.6 fW/cell before to 57.1 +/- 1.8 fW/cell after therapy (P less than 0.001). Similarily, adipocyte heat production was initially significantly lower than normal and increased during treatment in all 6 patients investigated. The mean value for heat production per adipocyte was 18.8 +/- 1.7 pW/cell before and 32.4 +/- 2.5 pW/cell after therapy (P less than 0.025), which is still below the level recorded in lean healthy subjects. The adipocyte size did not change significantly. The increase in adipocyte heat production was correlated to the increase in S-triiodothyronine levels (r = 0.84, P less than 0.05). In hypothyroidism, the total metabolic activity seems to be comparatively more reduced in adipocytes than in platelets. A difference may exist between these cells with regard to recovery of normal metabolic activity during treatment for hypothyroidism. Direct microcalorimetry appears to be an adequate method for monitoring net metabolic effects of thyroid hormones in these cells.
Twenty-eight haemodialysis patients were randomized to L-carnitine, 2 g i.v. three times a week, and saline over a 6-week period. No obvious deficiency of carnitine was found in vastus lateralis with a median value of 12.9 mmol/kg dry weight; range 6.2-21.4. Female patients had lower total plasma carnitine compared to female controls, p less than 0.002, whereas no decrease was found in males. No relationship was found between muscle and total plasma carnitine. After carnitine administration the muscle carnitine level increased about 60%, p less than 0.01, and the total plasma carnitine level more than tenfold, whereas the initially high degree of acylation decreased, p less than 0.02. Maximum dynamic muscular strength was reduced with a mean value of 44% compared with healthy controls. Total metabolic activity of isolated skeletal muscle fibres, measured as heat production with a new technique using a perfusion microcalorimeter, showed a median value of 0.40 mW/g, 25% lower than normal, p less than 0.02. Carnitine administration had no effect on several different tests of muscular function. Neurophysiologically, discrete improvements in the temperature responses were recorded, but no changes in sensory and motor nerve conduction velocities or in vibration thresholds were noted. No symptomatic improvement was observed even in patients with the lowest carnitine levels prior to treatment. Our data do not support the hypothesis that carnitine deficiency contributes to muscle and nerve dysfunction in patients on chronic haemodialysis.
The effects of L-carnitine administration (2 g i.v. three times weekly for 6 weeks) were studied in a double blind trial comprising 2 X 14 patients on regular haemodialysis treatment. The initial plasma carnitine concentrations were normal in the male, but slightly lowered in the female participants and rose more than ten-fold in the patients receiving active treatment. The majority (15/28) of patients had moderate hypertriglyceridaemia, whereas plasma HDL cholesterol levels were normal. Activities of hepatic and lipoprotein lipase were decreased and fat tolerance impaired. The S-triiodothyronine and/or thyroxine levels were subnormal in 11 patients. Four patients had fasting hyperinsulinemia, and 6 demonstrated abnormal B-glucose patterns after a peroral glucose load. The galactose elimination rate demonstrated moderately impaired hepatocyte function in four patients. No effects of carnitine treatment on any of the variables could be detected.
Left ventricular function was non-invasively studied in 28 randomly selected haemodialysis patients before and after administration of L-carnitine, 2 g i.v. three times per week or saline in a double blind designed study over a six-week period. Cardiac function variables showed no relationship to muscle (vastus lateralis) and plasma carnitine concentrations. No apparent deficiency in muscle carnitine was found, whereas total plasma carnitine was lower in female patients than in female controls, p less than 0.002. The echocardiographic left ventricular end-diastolic diameter was initially increased in about one third and the ejection fraction was depressed in about one fifth of the patients. An increased A:H ratio was found in 15%. Systolic time intervals were deranged in 30% of the patients. After carnitine administration, marked increases of muscle and plasma carnitine levels were found, p less than 0.01, but no effects were recorded in any of the cardiac tests. Muscle carnitine increased from 14.6 mmol/kg dry weight to a median of 23.7 mmol/kg. We found no support for the hypothesis that carnitine depletion is responsible for cardiac dysfunction in haemodialysis patients.
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The efficiency of the combination of four tumor markers in recognizing advanced (recurrent or metastatic) colorectal cancer was evaluated. In 31 normal volunteers and in 31 patients with histologically documented colorectal tumor, we measured serum levels of carcinoembryonic antigen (CEA), ferritin, anionic glycoproteins, and their sialic acid content (SA). CEA, ferritin, anionic glycoproteins and SA mean levels were significantly higher in patients than in normal subjects. Among the four markers CEA was the most sensitive (87.1%) and SA the most specific (100%). By using CEA and SA in combination in 29 out of 31 patients, either marker was abnormally high. Ferritin and anionic glycoproteins did not render additional information. CEA serum levels were elevated in 14 out of 15 patients with liver metastasis, while SA was elevated in six out of 15. CEA maintains its central cole as tumor marker in colorectal cancer; the combined use of CEA and SA may add to precision in detecting patients with advanced colorectal cancer. Anionic glycoproteins and ferritin seem of limited usefulness.
Functional activity of granulocytes from healthy individuals and from patients with acute leukemia in remission was studied. The increase of heat production rate (metabolic activity) after stimulation of the blood cells with in vitro formed immune complexes was measured by microcalorimeters of heat conduction type. It was demonstrated that increased heat production rate after exposure to immune complexes was significantly lower (p less than 0.0005) in 9 patients with acute leukemia with a remission duration of less than 6 months than in 25 healthy volunteers.
The case of an 81-year-old woman suffering for about 1 year from a typical form of Letterer-Siwe disease (LSD) is reported. The only important systemic involvement was hepatosplenomegaly. The patient was treated with steroids and vinblastine and then with thymopoietin pentapeptide. This last drug proved useful for decreasing the dose of steroid and thus for checking the appearance of new skin lesions. The ultrastructural investigations, carried out before and after vinblastine, showed the presence in some histiocytosis X cells (HXC) of coated Birbeck granules (BG). Immunoelectron microscopy showed about 90% of HXC to be OKT6+ and the OKT6 labeling of these cells to be similar to that of the Langerhans cells of normal skin. Five percent of OKT6+ cells apparently contained no Langerhans granules.
The metabolic activity of platelets in patients with advanced rheumatic heart disease (RHD) was estimated by measurement of heat production in a microcalorimeter. Twenty-nine patients were randomly selected and prospectively followed before and after valve replacement with Björk-Shiley prosthesis. Before the operation a significantly (P less than 0.02) elevated platelet heat production was found compared with normal subjects, 63 +/- 5 fW/cell and 59 +/- 4 fW/cell, respectively, probably due to the presence of a younger and metabolically more active platelet population. Platelet count before the operation was significantly lower than normal (P less than 0.001). Platelet heat production did not correlate with either type of valvular disease, the presence of valvular calcification or atrial fibrillation. After valve replacement the platelet heat production significantly decreased (P less than 0.001) to 58 +/- 5 fW/cell and the platelet count normalized. The highest incidence of thromboembolic manifestations was in the immediate postoperative period. The greatest reductions in platelet heat production. 19% and 27% were observed in two patients with thromboembolic events, as compared with an average of 4% for the rest of the operated patients without complications. The possible relationship between changes in platelet heat production and thromboembolism in patients with RHD is discussed.
Heat production rate in polymorphonuclear granulocytes (PMN) from 18 AML patients and 21 healthy individuals was measured using microcalorimetry. An increased PMN heat production rate was found in most AML patients at diagnosis and during the first 6 months of remission. In 7/7 patients showing values above the normal mean level the heat production rate decreased during sequential analysis. The increased PMN heat production rate is serum dependent and leukaemic sera induced increased calorimetric values also in PMN from healthy donors. This effect was not due to heat labile complement factors.