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Biomedical subjects

M Capra

Publications and source records attributed to M Capra.

At least 19 recordsLinked to original sources

Quantitative evaluation of oxidative stress status on peripheral blood in beta-thalassaemic patients by means of electron paramagnetic resonance spectroscopy.

High oxidative stress status (OSS) is known to be one of the most important factors determining cell injury and consequent organ damage in thalassaemic patients with secondary iron overload. Using an innovative hydroxylamine 'radical probe' capable of efficiently trapping majority of oxygen-radicals including superoxide we measured, by electron paramagnetic resonance (EPR) spectroscopy, OSS in peripheral blood of 38 thalassaemic patients compared with sex-/age-matched healthy controls. Thalassaemic patients showed sixfold higher EPR values of OSS than controls. Significantly higher EPR values of OSS were observed in those with a severe phenotype (thalassaemia major, transfusion-dependent) with respect to mild phenotype (sickle-cell/beta-thalassaemia, not transfusion-dependent) or thalassaemia intermedia. In patients with thalassaemia major, EPR values of OSS were positively correlated with serum ferritin and with alanine aminotransferase levels. In patients with sickle cell/beta-thalassaemia, there was no correlation between EPR value of OSS and all parameters considered. The type of chelating therapy (desferrioxamine or deferiprone) did not have an effect on EPR value of OSS. In conclusion, EPR 'radical probe' seems to be a valid innovative method to determine total OSS in patients affected by thalassaemia and might be used for evaluating new strategies of chelation, new chelators, or the efficacy of antioxidant formula.

Adult↗

Central nervous system tumours in adolescents.

Adolescents with brain tumours have been, and in most cases still are, haphazardly assigned, on referral, to either 'paediatric' or 'adult'-based treatment centres. In this age group, there is therefore a history of inconsistent treatment, delivery of inappropriate 'maturity-related' care and a reduced chance of gathering vital biological, clinical and treatment-related information germane to this group of patients and their tumours. These days, adolescents with brain tumours should be actively targeted for recruitment into clinical trials and admission into dedicated neuro-oncology centres or programmes that can deliver the necessary and age appropriate multidisciplinary management.

Adolescent↗

Bradykinin production during donor plasmapheresis procedures.

BACKGROUND AND OBJECTIVES: Extracorporeal circuits made of artificial substances may induce blood cells and humoral activation. Negatively charged surfaces may activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin (BK) production. BK has been considered to be involved in severe hypotensive reactions occurring during therapeutic apheresis in patients taking angiotensin-converting enzyme (ACE) inhibitors or in those receiving platelet transfusion. In this study we investigated BK production during donor plasmapheresis procedures. PATIENTS AND METHODS: Eighteen volunteer donors entered the study protocol. Nine of them were taking ACE inhibitors. Their blood pressure (BP) was monitored both pre- and post-apheresis, and BK determination was carried out using a competitive enzyme immunoassay (EIA), in plasma samples collected both during and at completion of the procedure. In addition, a limited number of thawed plasma units were checked for BK. RESULTS: No side-effects were observed during the procedures. However, donors taking ACE inhibitors showed a higher variation of their systolic BP compared to those who were not taking ACE inhibitors, while diastolic BP percentage variations did not differ significantly between the two groups. The BK concentration was considerably higher in donors taking ACE inhibitors: 183 +/- 26 versus 82 +/- 6 ng/ml (P < 0.0001) after the first collection cycle and 142 +/- 20 versus 65 +/- 11 ng/ml (P < 0.0001) in the final samples. BK was also detected, at a lower concentration (15 ng/ml), in one out of four thawed plasma units obtained from donors taking ACE inhibitors and at 1 ng/ml in one out of two thawed plasma units from the control group. CONCLUSION: Donors taking ACE inhibitors and undergoing plasmapheresis showed higher levels of BK compared to the control group. Furthermore, the detection of BK in plasma units after a freeze-thaw procedure might explain the sudden hypotensive reaction occurring during therapeutic plasma exchange when plasmapheresis units are adopted as substitution fluids. Further investigations are needed to assess the real clinical importance of the presence of BK in plasma units.

Adult↗

Heavy mining vehicle controls and skidding accidents.

This paper examines various control locations in heavy mining vehicles. Three trucks have been tested on a skid pad in both clockwise and anticlockwise directions. The skid lengths were measured after each trial. The primary focus of the study was the positioning of various controls and their relevance to various skid lengths. Some additional measures such as NASA-TLX scales were also used to make subjective evaluations. The results are presented in this paper. The findings clearly indicate the relevance of control locations to actual skid lengths. The poorly located controls resulted in greater skid lengths. This is an important finding as skid lengths are related to greater reaction times in a skidding situation and hence greater risk of accidents on relevant trucks. Such accidents can incur large repair bills for damaged equipment whereas more importantly, jeopardizing the life and safety of heavy mining vehicle drivers.

Accidents, Occupational↗

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Adolescent↗

[Pattern of spontaneous and post-stimulation FSH and LH in male adolescents with thalassemia].

BACKGROUND: In the last years thalassemic patients gained a good improvement in prognosis and life style. However, short stature and hypogonadism are still frequent endocrine problems in this population. METHODS: In a group of eleven thalassemic males (14-18 years old), the spontaneous nocturnal endocrine patterns of LH and FSH and plasma gonadotropins in response to GnRH were studied. The profiles were analyzed using a computer program (PULSAR) to determine the secretion pattern (number and amplitude of peaks) and the area under the curve above the secretion baseline (AUC). The endocrine status was compared with liver fibrosis, iron overload and transfusional regimen. RESULTS: A regular and homogeneous transfusion and chelation management often does not prevent pubertal failure; it is related with the degree of liver fibrosis and often it is due to hypothalamic and/or pituitary dysfunction. CONCLUSIONS: Spontaneous gonadotropin profiles can be useful to evaluate hypogonadotropic hypogonadism in order to start the correct treatment.

Adolescent↗

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult↗

Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.

Adolescent↗

Simultaneous onset of primary cutaneous B-cell lymphoma and human herpesvirus 8-associated Kaposi's sarcoma.

We report the simultaneous occurrence of Kaposi's sarcoma (KS) and primary cutaneous B-cell lymphoma (CBCL) of the leg in a 79-year-old woman, seronegative for HIV-1, HTLV-1 and HTLV-2. The CBCL underwent complete clinical remission after local radiotherapy, whilst the KS became disseminated within a year following diagnosis. However, 2 years after the diagnosis of KS, the patient died with neurological symptoms. These were presumed to be due to involvement of the central nervous system by lymphoma, although in the absence of an autopsy, this could not be proven. Skin biopsies from the original KS and CBCL lesions, as well as short-term culture of spindle cells from the KS lesion and peripheral blood mononuclear cells (PBMC), were studied by semiquantitative polymerase chain reaction (PCR) using primers specific for DNA sequences of a novel gamma-herpesvirus-8 (HHV-8). PCR studies were strongly positive for the virus on KS cells and PBMC; conversely, a low viral load was found on CBCL cells. A high titre of serum IgG antibodies reacting with the nuclei of the HHV-8 positive cell line BCP-1 was found. These data suggest that reactivation of latent infection with HHV-8 had occurred in this patient, and that HHV-8 is directly involved in KS, but not in CBCL of the leg, an aggressive variant of CBCL.

Aged↗

Restricted tissue distribution of extralesional Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS patients with Kaposi's sarcoma.

Specific herpesvirus-like DNA sequences have been found in Kaposi's sarcoma (KS) lesions of AIDS patients, suggesting that a novel gamma herpesvirus, homologous to Epstein-Barr virus and herpesvirus saimiri, could be implicated in the pathogenesis of KS. To better understand the role of this putative etiological agent, named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), we investigated by the polymerase chain reaction (PCR) the presence of viral DNA sequences in various organs obtained at autopsy from seven AIDS patients with KS and six without KS. For each sample, to exclude positive results due to visceral KS dissemination, the presence of microscopic foci of KS cells was rules out by histology and CD34 immunohistochemistry on serial frozen sections immediately adjacent to those employed for DNA extraction. PCR and nested PCR were performed with primers specific for the HIV-8 330 Bam fragment originally described by Chang et al. (Science 1994;266:1865-1869). As quality control, the extracted DNA was amplified with primers for human beta-globin. All KS legions were HHV-8 positive. In addition, extralesional KSHV DNA sequences were detected in seven of seven lymphoid organs and in five of five prostate glands of KS patients. Normal skin was positive in three of five cases and bone marrow in two of three tested cases, all other tissues being negative by PCR and nested PCR. By contrast, no virus was detected in tissue samples of AIDS cases without KS. The restricted organ distribution here documented argues for a selective tissue tropism of HHV-8 in vivo in AIDS patients and suggests that in the infected host lymphoid organs and the prostate gland may represent privileged sites of viral latency and persistence.

Acquired Immunodeficiency Syndrome↗

Treatment of autonomous thyroid nodules: value of percutaneous ethanol injection.

OBJECTIVE: Percutaneous injection of alcohol was recently proposed as an alternative to surgical and radioiodine treatments of autonomous thyroid nodules. The purpose of this study was to determine the value of this procedure and to define its limitations and indications when used for this purpose. MATERIALS AND METHODS: Thirty-one patients with autonomous thyroid nodules underwent a cycle of treatment with percutaneous injection of ethanol in multiple sessions (three to seven) on alternate days depending on the diffusion of the ethanol in the nodule. Fifteen patients were hyperthyroid, and 16 were euthyroid but had inhibited secretion of thyrotropin. The treatment results were evaluated by thyroid scintigraphy and sonography, by triiodothyronine, thyroxine, and thyrotropin assays, and by a thyrotropin-releasing hormone stimulation test 6 months after the end of treatment. Baseline scintigraphy demonstrated exclusive radionuclide uptake in the nodule in 29 patients and partial uptake in the extranodular tissue in two. The volume of the nodules ranged from 0.8 to 34.0 ml (mean +/- SD, 11.8 +/- 8.8 ml). Patients were monitored clinically for 24 hr after each session of ethanol injection to evaluate complications. Fifteen patients underwent a second cycle of ethanol injection when the results 6 months after the first cycle were unsatisfactory. The mean +/- SD follow-up was done at 26.9 +/- 12.3 months. RESULTS: Scintigraphy showed recovery of extranodular uptake of radionuclide in 72% of patients with nodules less than 13 ml in volume (maximum diameter [mean +/- SD], 2.7 +/- 0.7 cm; range, 1.4-4.0 cm) after one cycle of treatment and in 83% after two cycles. Among subjects with larger nodules, radionuclide uptake returned to normal in 9% after one cycle of treatment and in 9% after two cycles. For hyperthyroid patients, levels of thyroid hormones returned to normal in 69% after one cycle and in 77% after two cycles, and levels of thyrotropin returned to normal in 38% after one cycle and in 69% after two cycles; normal levels of thyrotropin were achieved in 93% of the euthyroid patients after one cycle of treatment and in 100% of these patients after two cycles. Symptoms resolved in 73% of the hyperthyroid subjects after the first cycle of treatment and in 93% of these subjects after the second. No important complications were observed; the most common side effects were acute pain at the injection site, referred pain, fever, transient dysphonia (< 12 hr), local hematoma, palpitations, and sinus tachycardia. CONCLUSION: Our results show that percutaneous injection of ethanol is appropriate therapy for autonomous thyroid nodules less than 13 ml in volume. The treatment should be considered successful when levels of thyroid hormones and thyrotropin return to normal. Nodule size appears to be the most important determinant of the success of the treatment. No complications that required termination of the treatment occurred.

Adult↗

Alpha interferon treatment of chronic hepatitis C in beta-thalassaemia.

In this open, pilot study, interferon (IFN) alpha-2b seemed effective in the treatment of hepatitis C virus (HCV) infection in patients with beta-thalassaemia. In seven of nine patients who completed the study alanine aminotransferase activities returned to normal, and a completely stable response 24 months after treatment was seen in five. Liver biopsy specimen showed a clear reduction in portal, periportal, and lobular necroinflammation in all five cases. Three patients stopped treatment early because of side effects.

Adolescent↗

A clinical study of the pineal hormone melatonin in patients with growth hormone or prolactin secreting pituitary tumours.

OBJECTIVES: Despite the well documented influence of the pineal gland on pituitary function, the evaluation of pineal activity is not generally included in the clinical investigation of patients with pituitary tumours. The present study analyzed the circadian secretion of melatonin, the main pineal hormone, in patients with pituitary adenomas. METHODS: The study included 36 patients with pituitary tumours (acromegaly: 11; prolactinoma: 25), by comparing the results with those seen in 42 healthy controls. Moreover, patients were endocrinologically investigated after oral administration of 10 mg of melatonin. RESULTS: Abnormally high serum levels of melatonin during the period of maximum light and abnormally low increases during the night were seen in 7/36 and 16/36 patients, respectively, without any relation to tumour histotype. Moreover, night serum mean levels of melatonin were significantly lower in patients than in controls. Finally, the exogenous administration of melatonin did not influence growth hormone and prolactin secretions in patients with acromegaly and prolactinomas, respectively. CONCLUSION: This study demonstrates the existence of an altered pineal function in patients with pituitary tumours. Further studies will be required to establish the pathogenetic and prognostic significance of pineal disorders in neoplastic disease of the pituitary gland.

Acromegaly↗