Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families.
(9/6100)
Point mutations in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia, an autosomal dominant disorder triggered in susceptible people (MHS) by volatile anaesthetics and depolarising skeletal muscle relaxants. To date, 17 missense point mutations have been identified in the human RYR1 gene by screening of the cDNA obtained from muscle biopsies. Here we report single strand conformation polymorphism (SSCP) screening for nine of the most frequent RYR1 mutations using genomic DNA isolated from MHS patients. In addition, the Argl63Cys mutation was analysed by restriction enzyme digestion. We analysed 57 unrelated patients and detected seven of the known RYR1 point mutations. Furthermore, we found a new mutation, Arg2454His, segregating with the MHS phenotype in a large pedigree and a novel amino acid substitution at position 2436 in another patient, indicating a 15.8% frequency of these mutations in Italian patients. A new polymorphic site in intron 16 that causes the substitution of a G at position -7 with a C residue was identified. (+info)
Mechanisms of beta-lactam resistance amongst Pseudomonas aeruginosa isolated in an Italian survey.
(10/6100)
The mechanisms of resistance to beta-lactam antibiotics in 325 isolates of Pseudomonas aeruginosa were examined. These isolates were selected because of their resistance to meropenem and imipenem (breakpoint, >4 mg/L), carbenicillin (>128 mg/L), ceftazidime (>8 mg/L), piperacillin and ticarcillin/clavulanate (>64 mg/L). The most frequent mechanism of resistance was beta-lactamase-independent, so called 'intrinsic resistance', which was found in 183 isolates and was probably due to impermeability and/or efflux mechanisms. beta-Lactamase-mediated resistance was demonstrated in 111 strains (11.1%). Derepression of Ambler Class C chromosomal beta-lactamase was detected in 64 isolates, most of which were resistant to ceftazidime and piperacillin but susceptible to meropenem, whereas secondary plasmid-encoded beta-lactamases were found in 34 isolates, all of them resistant to carboxypenicillins and ureidopenicillins and susceptible to carbapenems. Twelve strains showed more than one plasmid-encoded beta-lactamase plus derepression of chromosomal Class C enzyme. Resistance to carbapenems was independent of resistance to other beta-lactam antibiotics, indicating a different mechanism of resistance, probably due to the loss of the D2 porin. In total, 32 strains were resistant to carbapenems: 24 only to imipenem and eight to both imipenem and meropenem. (+info)
Neurocysticercosis in an Italian traveler to Latin America.
(11/6100)
Neurocysticercosis is rarely reported in short-term travelers, although the disease remains a major public health problem in tropical regions. We present a case of neurocysticercosis that was probably acquired by ingestion of Taenia solium eggs contained in the stomach of a pig butchered by the traveler. Complete clinical resolution was obtained by medical treatment, underlying the importance of early suspicion and diagnosis of the disease. (+info)
Prevalence and clinical outcome associated with preexisting malnutrition in acute renal failure: a prospective cohort study.
(12/6100)
Malnutrition is a frequent finding in hospitalized patients and is associated with an increased risk of subsequent in-hospital morbidity and mortality. Both prevalence and prognostic relevance of preexisting malnutrition in patients referred to nephrology wards for acute renal failure (ARF) are still unknown. This study tests the hypothesis that malnutrition is frequent in such clinical setting, and is associated with excess in-hospital morbidity and mortality. A prospective cohort of 309 patients admitted to a renal intermediate care unit during a 42-mo period with ARF diagnosis was studied. Patients with malnutrition were identified at admission by the Subjective Global Assessment of nutritional status method (SGA); nutritional status was also evaluated by anthropometric, biochemical, and immunologic parameters. Outcome measures included in-hospital mortality and morbidity, and use of health care resources. In-hospital mortality was 39% (120 of 309); renal replacement therapies (hemodialysis or continuous hemofiltration) were performed in 67% of patients (206 of 309); APACHE II score was 23.1+/-8.2 (range, 10 to 52). Severe malnutrition by SGA was found in 42% of patients with ARF; anthropometric, biochemical, and immunologic nutritional indexes were significantly reduced in this group compared with patients with normal nutritional status. Severely malnourished patients, as compared to patients with normal nutritional status, had significantly increased morbidity for sepsis (odds ratio [OR] 2.88; 95% confidence interval [CI], 1.53 to 5.42, P < 0.001), septic shock (OR 4.05; 95% CI, 1.46 to 11.28, P < 0.01), hemorrhage (OR 2.98; 95% CI, 1.45 to 6.13, P < 0.01), intestinal occlusion (OR 5.57; 95% CI, 1.57 to 19.74, P < 0.01), cardiac dysrhythmia (OR 2.29; 95% CI, 1.36 to 3.85, P < 0.01), cardiogenic shock (OR 4.39; 95% CI, 1.83 to 10.55, P < .001), and acute respiratory failure with mechanical ventilation need (OR 3.35; 95% CI, 3.35 to 8.74, P < 0.05). Hospital length of stay was significantly increased (P < 0.01), and the presence of severe malnutrition was associated with a significant increase of in-hospital mortality (OR 7.21; 95% CI, 4.08 to 12.73, P < 0.001). Preexisting malnutrition was a statistically significant, independent predictor of in-hospital mortality at multivariable logistic regression analysis both with comorbidities (OR 2.02; 95% CI, 1.50 to 2.71, P < 0.001), and with comorbidities and complications (OR 2.12; 95% CI, 1.61 to 2.89, P < 0.001). Malnutrition is highly prevalent among ARF patients and increases the likelihood of in-hospital death, complications, and use of health care resources. (+info)
Characterization of a new form of inherited hypercholesterolemia: familial recessive hypercholesterolemia.
(13/6100)
We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools per day, respectively; P<0.001) and a significant increase in the production rate [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB in the probands compared with normolipidemic controls. We then studied the in vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver. (+info)
Human herpesvirus 8 seroprevalence and evaluation of nonsexual transmission routes by detection of DNA in clinical specimens from human immunodeficiency virus-seronegative patients from central and southern Italy, with and without Kaposi's sarcoma.
(14/6100)
In order to investigate the seroprevalence of human herpesvirus 8 (HHV-8) infection in central and southern Italy, sera from human immunodeficiency virus (HIV)-seronegative subjects, with and without Kaposi's sarcoma (KS), were analyzed by immunofluorescence assay, using BC-3, a cell line latently infected with HHV-8. High titers of antibody against HHV-8 lytic and latent antigens were detected in all 50 KS patients studied, while in 50 HIV-seronegative subjects without KS, 32 (64%) were found positive for HHV-8 antibodies. Titers in the sera of these patients were lower than those for KS patients. This data suggests that HHV-8 infection is not restricted to KS patients and that the prevalence of HHV-8 infection in the general population may be correlated with differing rates of prevalence of KS in different parts of the world. In view of these findings, possible nonsexual transmission routes were evaluated. Nested PCR was used to test for the presence of HHV-8 DNA in saliva, urine, and tonsillar swabs from KS and non-KS patients. In KS patients, 14 out of 32 tonsillar swabs (43.7%), 11 out of 24 saliva samples (45.8%), and just 2 out of 24 urine samples (8.3%) tested positive for HHV-8 DNA. In the control group, on the contrary, none of the 20 saliva and 20 urine specimens was positive for HHV-8 DNA; only 1 out of 22 tonsillar swabs gave a positive result. This data supports the hypothesis that HHV-8 infects the general population in a latent form. The reactivation of viral infection may result in salivary shedding of HHV-8, contributing to viral spread by nonsexual transmission routes. (+info)
rpoB mutations in multidrug-resistant strains of Mycobacterium tuberculosis isolated in Italy.
(15/6100)
Mutations of rpoB associated with rifampin resistance were studied in 37 multidrug-resistant (MDR) clinical strains of Mycobacterium tuberculosis isolated in Italy. At least one mutated codon was found in each MDR strain. It was always a single-base substitution leading to an amino acid change. Nine different rpoB alleles, three of which had not been reported before, were found. The relative frequencies of specific mutations in this sample were different from those previously reported from different geographical areas, since 22 strains (59.5%) carried the mutated codon TTG in position 531 (Ser-->Leu) and 11 (29.7%) had GAC in position 526 (His-->Asp). (+info)
Parental hyperdynamic circulation predicts insulin resistance in offspring: The Tecumseh Offspring Study.
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Controversy surrounds the pathogenetic mechanisms of the relationship between hyperdynamic circulation and insulin resistance. Two hundred eight children and young adults (mean age, 17.2+/-3.0 years; range, 11 to 26 years) from the Tecumseh Offspring Study whose parents had been assessed with Doppler echocardiography at the age of 34 years during the previous Tecumseh Blood Pressure Study were considered for this analysis. Offspring data were stratified according to tertiles of parental cardiac index. Parents in the top cardiac index tertile had increased heart rate (P=0.001), stroke volume (P=0.0001), left ventricular fractional shortening (P=0.02), and plasma epinephrine (P=0.02) compared with parents in the other tertiles. Body mass index (BMI) and blood pressure were similar in all groups. Offspring of parents with a high cardiac index had greater BMI (P=0.001), skinfold thickness (P=0.008), and waist/hip ratio (P=0.02), higher diastolic blood pressure (P=0.02) and plasma insulin level (P=0.001), and higher heart rate during Stroop's color test (P=0.02) than offspring of parents with a lower cardiac index. In a multivariate regression analysis, offspring BMI was predicted by parental BMI and cardiac index (P=0.0001 and 0.003, respectively). The mother-child relationship explained most of the cardiac index-BMI association. In summary, parental hyperdynamic circulation was an important predictor of overweight, abnormal fat distribution, increased blood pressure, and hyperinsulinemia in offspring. Our results illustrate the complexity of interaction between a genetic tendency and its phenotypic expression. We speculate that the degree of beta-adrenergic responsiveness may be a major determinant of the phenotypic differences between the parents and offspring found in this study. (+info)