Factitious hypermineralcorticoidism by chronic use of 9-alpha-fluoroprednisolone containing collyrium.
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Biomedical subjects
Publications and source records attributed to M Grilli.
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The relation among hand, foot and eye lateral preference indices and certain verbal ability tests was studied in a group of 497 elementary school children. According to the performance on the verbal ability tests, the original sample was divided into a Lower and an Upper Group, and percentages of left preferences, consistent right and left preferences, crossed hand-foot, hand-eye, foot-eye preferences and congruent preferences were compared. The only comparison that proved to be significant was the evidence of a lower left preference percentage in reading speed in the Upper Group as compared to the Lower Group. A similar series of comparisons between a subgroup (N = 14) of children with serious reading problems and the group as a whole, did not lead to significant results. We therefore conclude that at least for subjects regularly attending school, there is no relation among lateral preference and the above mentioned verbal skills.
The mesolimbocortical dopaminergic system innervates several brain regions including the frontal cortex. The aim of our work was both to identify and to pharmacologically characterize the dopamine receptors located in this brain area. We found that different selective agonists for D1 receptors were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover different agonists for D2 receptors inhibited the cyclic AMP generating system, and these effects were prevented by (-)-sulpiride. According to the paradigm that D1 receptors are linked with adenylate cyclase in a stimulatory way, while D2 receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat frontal cortex.
The mesolimbocortical dopamine (DA) system innervates several brain regions including the hippocampus. The aim of the present study was both to identify and to pharmacologically characterize the DA receptors located in this brain area. The results show that different agonists for D1 DA receptors, such as DA itself, SKF82526 and (-)-apomorphine, were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover bromocriptine, lisuride and RU 24213, which are agonists for D2DA receptors, inhibited the cyclic AMP generating system and these effects were prevented by (-)-sulpiride. According to the paradigm that D1 DA receptors are linked with adenylate cyclase in a stimulatory way, while D2 DA receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat hippocampus. Localization studies show that both DA receptor subtypes are restricted to the dorsal part of the hippocampus.
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It is well documented (1-3) that a balanced use of nutritive solutions is important to maintain metabolic homeostasis and a better control of nutrient flux in fasting patients. In this trial, 10 healthy males, aged 30-50 years, fasted for 12 h, were subjected to intravenous nutrient loads in three separate trials. In the first trial they received only a fat emulsion, in the second fat emulsion and L-amino acid solution, and in the third fat emulsion, L-amino acid solution and glucose solution, 240 and 480 min after intravenous infusion plasma triglycerides, serum cholesterol, free fatty acids, lactate, glucose and plasma amino acids were determined. Significant biochemical changes were detected with regard to triglycerides, lactic acid, free fatty acids, alanine, glutamine, lysine and proline concentrations, depending on the different mixtures utilized.
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Carnitine is a selective carrier of free fatty acids from the cytoplasm to the mitochondria. Dialysed patients are chronically and progressively carnitine deficient due to loss in the dialysate. Simultaneously such patients present impaired lipid metabolism and this may provoke varied pathological conditions ranging from isolated hypertriglyceridaemia to frank forms of hyperlipoproteinaemia types IIa, IIb, and IV, and to apparently normolipaemic situations falling within a lipoprotein pattern tending to become pathological with low levels of HDL-cholesterol. In the present investigation we evaluated the effect of l-carnitine (versus placebo) on the lipid pattern in a group of apparently normolipaemic dialysed patients, but with altered coronary risk factors (HDL-cholesterol, beta:alpha lipoprotein ratio). Examinations showed no significant changes at the 15th and 30th day of placebo treatment, whereas the l-carnitine treated group displayed a statistical significant increase in HDL-cholesterol accompanied by reduced pre-beta-lipoproteins and decreased beta:alpha ratio.
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Chemical determination of total and esterified cholesterol and electrophoretic separation of plasma lipoproteins was carried out in a chemico-clinical approach to the pathology of lipide metabolism in pregnancy. In a future study, the investigation will be extended to the neonatal aspect of the problem. 136 women were studied, with 446 samples being taken, specifically: 65 controls, i.e. pregnant women not presenting pathology that might obviously involve lipide metabolism, 36 hypertense pregnant women, 28 diabetic and 7 with gravidic hepatosis. Observation of the data confirms that in pregnancy there is a steady, meaningful increase in cholesterolaemia and that the electrophoretic picture shows a steady reduction in alpha-lipoproteins, with stimulatneous increase in pre-beta proteins, reaching a peak in hepatosis cases, and an increase in beta lipoproteins. All this agrees with functional and teleological modifications in lipide metabolism during gestation.
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Exposure of primary cultures of cerebellar granule cells for 15 min to micromolar concentrations of glutamate results in cell death of both necrotic and apoptotic types. Among the intracellular events triggered by glutamate, we identified two transcriptional factors: the p50 member of the NF-kappaB family and the tumor suppressor phosphoprotein p53. Pretreatment of the cultures with aspirin, which inhibits NF-kappaB activation, or with specific p53 antisense oligonucleotide, which inhibits p53 transcription, resulted in a complete prevention of glutamate-induced p53 induction and apoptosis. These findings suggest the existence of a transcriptional program activated by glutamate receptor stimulation in which p50 and p53 play a relevant role. Then, we studied the expression of two p53 downstream genes that could participate in the glutamate-induced pro-apoptotic pathway: p21, which codes for an inhibitor of different cyclin dependent kinases, and MSH2, which codes for a protein involved in the recognition and repair of DNA mismatches. We found that primary cerebellar neurons expressed p21 and MSH2 at very low levels in basal conditions. However, very soon after a brief exposure of the cells to glutamate, the expression of both proteins was dramatically enhanced.On these bases, we propose NF-kappaB, p53, p21 and MSH2 as relevant contributors of the glutamate-induced pro-apoptotic pathway. Understanding this cascade of nuclear events may unravel specific targets for pharmacological intervention for those neurological diseases in which excitatory amino acid-induced apoptosis plays a relevant role.
The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.
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INTRODUCTION: Even if infrequent, a digital necrosis after chemotherapy can occur in cancer patients. The gemcitabine is generally well tolerate; the cutaneous toxic ulcerations only in 0.3% of the cases induces the suspension of the treatment. CLINICAL CASE: A 70 year old patient, female, with a bladder cancer, after a trans-urethral resection, is submitted to adjuvant chemotherapy with Gemcitabine 1700 mg (total dose/die), with administration in the days 1st and 8th, while in the 15th day was not effected because, to distance of 3-4 days from the second administration, appear paresthesies of the fingers of the hands, together with Raynaud type phenomenon, 38-39 degrees C intermittent fever, digital necrosis and fingertips gangrene. Laboratory: (Normal): RF; AutoAb: AMA, ASMA, APCA, anti-DNA; ENA; lupus anti-coagulant; Ab-anti-cardiolipin; C3-C4, CIC; homocysteine, anti-thrombin, protein C, protein S, mutation of the factor V of Leiden, plasminogen, alfa 2-antiplasmin. (Altered): Auto-antibody: ANA (on Hep-2): positive (title 1/160, speckled pattern), cryoglobulin positive, ESR 29; Instrumental examinations: Superior Limbs Angiograpy: Occlusion of the digital arteries proper of 2nd, 3rd and 4th finger of the hands. Electromyography Inferior Arts: normal. Superior Arts: bilateral suffering of the median nerve at the carpal tunnel. Biopsy of the hand cutis: Hyperkeratosis, acanthosis and papillomatosis of the skin. Arterial vases with signs of endothelioangiitis and aspecific inflammation. CONCLUSIONS: Even if acronecrosis of the superior limbs is a rare effect of the gemcitabine, we would recommend particular caution in the administration of this drug in patient with known autoimmune disorders.