In vivo evaluation of leukocyte distribution by means of technetium 99m after intravenous administration of high doses of recombinant erythropoietin.
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Animals↗
Biomedical subjects
C Conte
Publications and source records attributed to C Conte.
Prognostic significance of metabolic changes detected by proton magnetic resonance spectroscopy in ischaemic stroke.
Proton magnetic resonance spectroscopy has proved to be useful for monitoring a number of metabolites in cerebral infarction. Combined magnetic resonance imaging and spectroscopy investigations were carried out in 14 patients with a recent ischaemic stroke (< 1 week); follow-up examinations were performed from day 28 to day 252 after stroke. The aim of this study was to assess the correlation between the changes of N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate and clinical evolution measured by the Scandinavian Neurological Scale (SNS). Initially the lactate magnetic resonance signal was present in all patients and the other metabolite contents were significantly reduced (P < 0.001; unpaired t-test) as compared with those on the contralateral side. Spearman's rank correlation test showed a positive correlation between the initial reduction of N-acetyl-aspartate content and the SNS (P < 0.05), and between the final N-acetyl-aspartate content and the SNS (P < 0.001). Our results suggest that serial examination in stroke patients may provide further prognostic information and encourage controlled clinical studies.
Adult↗
99Tcm-HMPAO SPET and 1H-MRS (proton magnetic resonance spectroscopy) in patients with ischaemic cerebral infarction.
Brain 99Tcm-HMPAO single photon emission tomography (SPET) and 1H-MRS (proton magnetic resonance spectroscopy) were used to determine correlations between alterations in regional cerebral blood flow (rCBF) and changes in neuronal metabolites in 21 patients (28 examinations) with ischaemic cerebral infarction examined in different phases. rCBF was determined semi-quantitatively using Lassen's linearization algorithm. SPET provided evidence of the hypoperfused site of necrosis within a few hours after the acute event and alterations in rCBF were detected in both the infarcted and diaschistic areas at all stages. 1H-MRS was used to monitor the concentration of the following metabolites: N-acetyl-aspartate (NAA), creatine and phosphocreatine (CR + PCr), compounds containing choline (Cho) and lactate (Lac). A significant correlation was found between reduction in rCBF and a fall in NAA and Cr + PCr in both the acute and chronic phases, but not during "luxury perfusion' in the subacute phase. The presence of LAC in the infarcted area up to 9 months post-ictus was totally unexpected. Simultaneous SPET and 1H-MRS thus provides additional information regarding the physiopathogenesis of cerebral ictus by clarifying the relation between alterations in rCBF and biochemical neuronal changes. We believe that NAA and Cr + PCr concentrations are the best expression of agreement between flow and metabolism in infarcted areas, particularly with regard to hypoperfused areas not clearly detectable by magnetic resonance imaging in the early post-ictus stage.
Adult↗
HLA and ethnic associations among systemic sclerosis patients with anticentromere antibodies.
SSc with ACAs is characterized by limited cutaneous involvement and, in most patients, a mild protracted course. We have studied 104 SSc patients, 47 with ACAs and 57 who were negative for both ACAs and anti-topo I antibodies, for HLA-DR and -DQ associations using DNA typing techniques. Normal controls consisted of 181 healthy individuals. A significant association was observed in the ACA-positive patients with DQB1-0501 (p = 0.001, RR 2.6). There was also a significant decrease in the frequency of DQB1-0201 (p = 0.01, RR 0.33). In addition, the ACA-positive SSc patients were significantly different ethnically from both the other SSc patients and the normal controls (p = 0.004). When patients were stratified according to their ethnic origin and the analysis of HLA associations was repeated, the HLA associations persisted. These results strongly suggest that the development of SSc with ACAs is associated with particular DQB1 alleles, and also that ethnic origin plays a role in disease susceptibility.
Adult↗
Severe restrictive lung disease in systemic sclerosis.
OBJECTIVE: We sought to identify risk factors for developing severe restrictive lung disease and to determine the time of onset and rate of progression in patients with systemic sclerosis (SSc). METHODS: Using the University of Pittsburgh Scleroderma Databank, we grouped patients according to their lowest forced vital capacity (FVC) value: > 75% predicted, 50-75% predicted, and < 50% predicted. In patients with severe restrictive disease, we examined serial pulmonary function test (PFT) results to determine the rate of loss of lung volume over time. RESULTS: Of 890 SSc patients, 60% (n = 531) never had an FVC < or = 75% predicted; 27% (n = 243) had moderate restrictive disease, with an FVC value of 50-75% predicted; and only 13% (n = 116) of the patients had severe restrictive disease, with FVC < or = 50% predicted. Black race, male sex, early disease, and primary cardiac involvement due to SSc were the features most frequently associated with severe restrictive lung disease (by multiple logistic regression). Fifty-five patients with severe restrictive lung disease had their first of at least 2 PFTs during the first 5 years after onset of any SSc (not pulmonary) symptoms. In 30 patients, the FVC declined by 32% per year in the first 2 years of illness, in 16 patients the annual loss was 12% in years 2-4 after disease onset, and in 9 patients annual loss was 3% during years 4-6 of disease (P < 0.005 by 1-way analysis of variance). CONCLUSION: In SSc patients, black men with early disease who have cardiac involvement are the most likely to have factors associated with the development of severe restrictive lung disease (which is increasingly becoming a major cause of death). Disease subtype (diffuse versus limited cutaneous) and serum anti-topoisomerase I antibody do not differentiate between moderate and severe restrictive disease. Careful monitoring of pulmonary function early in the disease, when the greatest loss of lung function occurs, may help identify patients likely to respond to new therapy.
Adult↗
Therapy for severe interstitial lung disease in systemic sclerosis. A retrospective study.
OBJECTIVE: This retrospective observational study attempted to determine whether any of the therapies used in the management of systemic sclerosis (SSc) patients held potential benefit for patients with interstitial lung disease. METHODS: All patients with SSc who had a pulmonary function test (PFT) showing a forced vital capacity (FVC) of < 70% predicted and an additional PFT at least 4 months later were grouped according to the treatment they received. Changes in pulmonary function were analyzed by the mean percent predicted FVC from the initial and the final test, and by the rate of percent change in FVC (ml/year) in the first 2 years after therapy. Bronchoalveolar lavage was performed in a subset of these patients. RESULTS: Of 363 SSc patients who had an FVC < 70% predicted, 122 had a second PFT and fulfilled the criteria for one of the following drug groups: high-dose prednisone (n = 21), immunosuppressive other than cyclophosphamide (CYC) (n = 16), CYC (n = 14), D-penicillamine (n = 37), or no drug (n = 34). In both analyses, the CYC-treated group showed significantly more improvement in FVC than did the other groups. Patients with early disease had the greatest likelihood of responding to any drug. CONCLUSION: This retrospective study shows that patients treated with CYC had a significant improvement in FVC over time. Prospective controlled studies of CYC treatment in early disease are necessary to determine if it can significantly alter the natural history of interstitial lung disease.
Adult↗
Proton magnetic resonance spectroscopy in patients with ischemic stroke.
Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive technique which has proved to be useful for monitoring various brain metabolites (N-acetyl-aspartate, choline, creatine-phosphocreatine, lactate). A total of 18 patients underwent a combined magnetic resonance imaging (MRI)/1H-MRS protocol in order to evaluate the distribution of the metabolites in the various stages of cerebral ischemia. Our results show a marked decrease of N-acetyl-aspartate and a large content of Lactate during the early phases, and a decrease in N-acetyl-aspartate, choline and creatine-phosphocreatine (Cr-PCr) during the chronic phase.
Adult↗
Cerebral ischemia: magnetic resonance angiography and transcranial Doppler evaluation.
We examined 21 patients with ischemic cerebrovascular disease using magnetic resonance angiography and transcranial Doppler. In 17 patients (81%), the results obtained by the two methods were concordant. In our opinion, the associated use of transcranial Doppler and magnetic resonance angiography provides an accurate diagnostic evaluation of ischemic stroke patients, not only allowing the site of possible steno-occlusive disease of large and medium cerebral vessels to be identified, but also offering the possibility of obtaining dynamic information concerning the direction of blood flow in the presence of compensatory circulations at the level of Willis' circle.
Adult↗
Severe systemic sclerosis with anti-topoisomerase I antibodies is associated with an HLA-DRw11 allele.
SSc is an autoimmune connective tissue disease in which strong HLA associations have not been described. Anti-topo I antibodies are recognized, in general, in SSc patients with diffuse cutaneous involvement, whereas anti-ACAs are found in individuals with limited cutaneous involvement. We studied 95 Caucasian SSc patients, 44 with anti-topo I antibodies and 51 with neither anti-topo I nor ACA, for HLA-DR associations by using DNA typing techniques. We analyzed 181 normal Caucasian individuals in the same fashion. A significant association was observed in the anti-topo-I-positive patients with DRw11 (p = 1.7 x 10(-6), RR 4.2). The distribution of DRw11 alleles in these patients was significantly different from that observed in controls and could be accounted for by an increase in the frequency of the DRB1*1104 allele (p = 1.2 x 10(-9), RR 9.5). The DRw11 alleles were also associated with SSc with more tendon friction rubs (p = 0.006), which is a marker of more severe disease. In addition, a strong association was observed with anti-topo I antibodies and a particular sequence (aa 71-77) of the DQB1 chain (p = 0.02, RR 2.2). HLA associations in the case of SSc patients with anti-topo I antibodies are complex and involve at least two genes: HLA-DRw11, which appears to play a major role in determining the severity of the disease, and a DQ sequence, which associates with the development of the anti-topo I antibodies.
Adult↗
[Retroperitoneal ganglioneuroma. A case report and review of the literature].
Ganglioneuromas are typically of slow growth and benign evolution and may remain clinically silent for a considerable time if favourably situated. Many large examples are discovered incidentally on X-ray examination, routine abdominal palpation or at necropsy. Ganglioneuromas are often encountered in childhood and are found more frequently in the posterior mediastinum than in any other single situation; other sites are the lumbar and pelvic retroperitoneal tissues, the gastrointestinal tract and the mesentery. Diffuse alimentary tract ganglioneuromatosis has been described as port of the multiple endocrine neoplasia syndrome (MEN) type II-B. Sometimes ganglioneuromas are found in the von Recklinghausen Syndrome. The authors report in this paper a rare case of a retropancreatic ganglioneuromas.
Female↗
[Malignant tumors or the small intestine. Review of the literature and report of a clinical case].
The authors present one case of patients with adenocarcinoma of the small bowel. Primary malignant tumors of the small intestine are uncommon neoplasms accounting for 1-2 per cent of all gastrointestinal malignancies. Patients are usually seen late in the course of their illness when curative therapy is unlikely. The rarity of these neoplasms explains in part why the early signs and symptoms frequently go unrecognized and is undoubtedly a major factor contributing to their poor prognosis. Despite a fourfold greater length and a nearly tenfold greater mucosal surface area, the incidence of adenocarcinoma of the small intestine is about a fortieth that of the colon. This relative immunity of the small bowel to the development of the malignant tumors is unexplainable. Several theories have been suggested and include the following: a) the rapid transit time of the small intestine may reduce its exposure to dietary carcinogens; b) the relative sterility of the small intestine compared with the colon may lessen the formation of carcinogenic substances by the action of bacteria on components of bile or other substances within the intestinal lumen; c) certain mucosal enzymes such as benzopyrene hydroxylase that detoxify potential carcinogens are present in higher concentrations in the small intestine than in the colon; d) immunoglobulin A which is found in high concentrations in the small bowel, may protect it against carcinogenic viruses. Interestingly, patients deficient in IgA and those receiving immunosuppressive therapy have been found to have a higher incidence of small intestinal cancer. Adenocarcinoma is the most common primary malignant small bowel neoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma↗
Isolated diffusing capacity reduction in systemic sclerosis.
OBJECTIVE: To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS: Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS: An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION: Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.
Carbon Monoxide↗
A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke.
Attention has focused on naloxone, an opiate receptor antagonist, because of its potential benefit in reversing neurological damage after acute cerebral ischemia. To evaluate the safety and possible efficacy of high-dose naloxone in ischemic stroke patients we planned a double blind pilot study. Between January 1989 and May 1990 24 patients were randomly assigned to the naloxone or placebo group according to age and neurological deficit. Naloxone was given in a loading dose of 5 mg/kg over 10 minutes followed by a 24-hour infusion at the rate of 3.5 mg/kg/h. 10 patients experienced minor side effects but none of them had to discontinue the treatment. 9 patients improved: 6 in the naloxone group and 3 in the placebo group, but no significant difference was found using the non parametric Mann-Whitney test. Our study suggests that naloxone is safe at the dose used, but the results do not support the planning of similar trials on a larger scale.
Acute Disease↗
Pregnancy in women with systemic sclerosis.
We assessed fetal morbidity and mortality in women with systemic sclerosis (SSc). Women with a history of SSc and a concomitant pregnancy completed a detailed questionnaire about the pregnancy. These 48 subjects were age-matched and race-matched to 2 other groups of women (a rheumatoid arthritis group and a control group from the same neighborhood), all of whom had been pregnant at least once. There were no differences in the frequencies of miscarriage or perinatal death in the SSc group compared with the 2 control groups. Preterm births occurred slightly more frequently in both SSc patients and rheumatoid arthritis patients compared with the neighborhood control subjects. There were significantly more small full-term infants born to women with SSc. Interestingly, the increase in preterm births and small full-term babies occurred with equal frequency prior to and after the onset of disease. Although close monitoring for premature birth and intrauterine growth retardation is necessary, we conclude that an uneventful, healthy pregnancy is possible for women with SSc. Those with early, rapidly progressive, diffuse skin thickening should avoid becoming pregnant since, intrinsically, they are at higher risk of developing renal crisis.
Abortion, Spontaneous↗
[Choice of parameters for the estimation of hazards in dusty work environments].
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Dust↗
[Preliminary study of the action of L.S.D. In 25 animals; Experimental catatonia in the pigeon].
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Catatonia↗
Endocrine and neuropsychological assessment in a child with a novel mutation of thyroid hormone receptor: response to 12-month triiodothyroacetic acid (TRIAC) therapy.
OBJECTIVE: To determine the endocrine, neuropsychological and genetic features of a child with resistance to thyroid hormone (RTH), and his response to long-term triiodothyroacetic acid (TRIAC) therapy. METHODS: Growth, thyroid function, and neuropsychology were assessed at baseline and during 12-month TRIAC therapy. Genetic analysis was performed by PCR and denaturing high performance liquid chromatography. RESULTS: The main clinical finding was the attention deficit-hyperactivity disorder (ADHD). A novel mutation in exon 10 (phenylalanine to isoleucine in codon 455) was found. Long-term TRIAC therapy was effective in the management of the endocrine and neuropsychological manifestations of the syndrome. CONCLUSIONS: ADHD was the only phenotypic manifestation of this novel mutation of thyroid hormone (TH) receptor. TRIAC is an effective and safe drug in the long-term treatment of children with RTH.
Child↗
Agonist and inverse agonist efficacy at human recombinant serotonin 5-HT1A receptors as a function of receptor:G-protein stoichiometry.
Membrane preparations were made from Chinese Hamster Ovary (CHO) cells expressing 1.6 and 4.2 pmol/mg of recombinant human 5-HT1A receptors, as determined by saturation binding with the selective antagonist, [3H]-S 15535 ([3H]-4-(benzodioxan-5-yl)]-(indan-2-yl)piperazine). There was no change in the number of G-proteins activated by the full agonist, serotonin (5-HT; approximately 1.1 pmol/mg in each preparation, measured by [35S]-GTP gamma S saturation binding), therefore increasing the receptor:G-protein ratio from approximately 1.4:1 (RGlow) to approximately 4:1 (RGhigh). Agonist efficacy was measured by stimulation of [35S]-GTP gamma S binding. The serotonergic agonist, eltoprazine, behaved as a partial agonist (Emax = 52.7%) at RGlow membranes but virtually as a full agonist (Emax = 93.2%) at RGhigh membranes, relative to 5-HT (= 100%). The latter exhibited a two-fold shift to the left in its concentration-response curve in RGhigh compared to RGlow membranes (P < 0.01). WAY 100,635 (N-¿2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl¿-N-(2-pyridinyl) -cyclo-hexane-carboxamide), did not alter [35S]-GTP gamma S binding from basal levels in either membrane preparation. In contrast, spiperone displayed inverse agonist activity, decreasing [35S]-GTP gamma S binding from basal levels by 17% in RGlow membranes but by 28% in RGhigh membranes. These data indicate that an increased receptor:G-protein ratio (i) augments the potency of full agonists, (ii) increases the efficacy of partial agonists and (iii) increases the negative efficacy of inverse agonists at recombinant human 5-HT1A receptors. Furthermore, these data suggest that spiperone induces, or stabilises, a G-protein-coupled, but inactive conformation of the receptor.
8-Hydroxy-2-(di-n-propylamino)tetralin↗