Patients monosensitised to Hev b 8 (Hevea brasiliensis latex profilin) may safely undergo major surgery in a normal (non-latex safe) environment.

BACKGROUND: Natural rubber latex allergy is a condition at high risk of anaphylaxis during surgery. However, latex contains several protein allergens and not all of them may show the same clinical relevance. OBJECTIVE: To investigate the clinical relevance of Hey b 8, the natural rubber latex profilin. METHODS: Seven patients without a clinical history of latex allergy but identified as being latex hypersensitive by positive SPT (3/7) and or positive latex-specific IgE during routine pre-surgery allergy investigations were studied. All patients were monosensitized to Hev b 8 (Hevea brasiliensis latex profilin) as shown by the detection of specific IgE to recombinant latex allergen components. Ten subjects with a history of latex allergy (urticaria, asthma, and/or rhinitis), sensitised to latex allergens other than profilin were enrolled as controls. Both patients and controls underwent a latex glove-wearing test; in case of a negative test, patients underwent surgery in a normal surgical setting. RESULTS: All 7 patients scored negative on latex glove wearing test and underwent major surgery (orthopaedic, Caesarean section, pilonidal sinus, vascular, tonsillectomy, uterine revision, and uretral surgery) in a normal (non-latex safe) surgical setting without any consequence. In contrast, 9/10 (90%) controls showed a positive latex glove-wearing test (p < 0.01). CONCLUSION: Latex profilin is either clinically irrelevant or is no longer present in latex products. This study highlights the importance of a component-resolved diagnosis of latex sensitisation as a tool to get a more precise assessment of the risk and to reduce the costs of healthcare.

Prognostic role of B-type natriuretic peptide in patients with diabetes and acute decompensated heart failure.

BACKGROUND: Several studies have reported the prognostic value of natriuretic peptides, but their predictive value in patients with diabetes mellitus is unknown. The aim of the study was to test the hypothesis that measurement of brain natriuretic peptide (BNP) levels in ambulatory patients with congestive heart failure (CHF) and diabetes can predict the occurrence of cardiovascular events at 6-month follow-up. METHODS: We enrolled 145 consecutive patient with diabetes [age 72 +/- 9 years, hypertension (21%), ischaemic heart disease (52%), atrial fibrillation (22%), preserved left ventricular function (29%)] seen in the outpatient heart failure clinic after an acute episode of cardiac failure. RESULTS: The median (25th/75th interquartile range) BNP concentrations at discharge were 186 (75-348) pg/ml. At 6-month clinical follow-up 10/145 (7%) subjects had died and 31/145 (21%) had been readmitted because of cardiac decompensation. BNP values of 200 and 500 pg/ml were found to have the best compromise between sensitivity (88 and 46%, respectively) and specificity (71 and 89%, respectively) for predicting events at 6 months. Multivariate Cox regression analysis identified only two parameters as predictors of events: serum creatinine [hazard ratio (HR) = 3.3; P = 0.02], and BNP plasma level BNP cut-off values (HR = 3.8; P = 0.03 for 201-499 pg/ml and HR = 7.7; P = 0.001 for > or = 500 pg/ml). CONCLUSION: These results suggest that BNP and serum creatinine are strong predictors of clinical events in patients with diabetes and CHF. In these patients, clinical outcome might be stratified by plasma BNP levels.

Relationship between B-type natriuretic peptide levels and ventilatory response during cardiopulmonary exercise test in patients with chronic heart failure.

AIM: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2). METHODS: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35. RESULTS: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01). CONCLUSIONS: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.

X/autosomal translocations in the Xq critical region associated with premature ovarian failure fall within and outside genes.

Premature ovarian failure curtails female reproductive life and is often linked to balanced Xq/autosomal translocations in a critical region. We mapped regions around translocations at the edges of this zone (one in Xq13.3, two in Xq26) in large-insert clones and analyzed their sequence. One Xq26 region is extensively transcribed and, in agreement with a recent independent analysis, the breakpoint interrupts a gene that encodes a widely expressed peptidase. In contrast 430 kb around the second Xq26 breakpoint has no putative or detected gene content. In 260 kb around the Xq13 translocation, the breakpoint falls among a cluster of repetitive elements at least 59 kb from the only detected gene (a rarely expressed T-box family transcription factor). We discuss our results in relation to models that ascribe premature ovarian failure to interruption of ovarian genes or to a failure of interactions involving DNA of the critical region during follicle development.

Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT).

Congenital amegakaryocytic thrombocytopenia (CAMT) without physical anomalies is a rare disease, presenting isolated thrombocytopenia and megakaryocytopenia in infancy, which can evolve into aplastic anemia and leukemia. Recently, two heterozygous truncating mutations of the thrombopoietin (TPO) receptor MPL, coded by the c-mpl gene, were identified in a 10-year-old Japanese patient with CAMT transmitted in an autosomal recessive manner. Here, we report for the first time two different MPL amino-acid substitutions in a 2-year-old Italian boy with CAMT and compound heterozygosis for two (c-mpl point mutations. C-to-T transitions were detected on exons 5 and 12 at the 769 and 1904 cDNA nucleotide positions, respectively. The mutation in exon 5 substitutes an arginine with a cysteine (R257C) in the extracellular domain, 11 amino acids distant from the WSXWS motif conserved in the cytokine-receptor superfamily. The mutation in exon 12 substitutes a proline with a leucine (P635L) in the last amino acid of the C-terminal intracellular domain, responsible for signal transduction. As in the Japanese family, the mutations were both transmitted from the parents. TPO plasma levels were highly increased in the patient. The patient's 7-year-old brother, who was a candidate donor for allografting, turned out to be an asymptomatic heterozygous carrier of P635L and showed defective megakaryocyte colony formation from bone-marrow progenitor cells. The present study provides important confirmation that CAMT can be associated with (c-mpl) mutations.

Combined gallopamil and isosorbide-5-mononitrate in "mixed" angina pectoris.

The efficacy of combining gallopamil and isosorbide-5-mononitrate (IS-5-MN) was evaluated in 15 patients with "mixed" angina and documented coronary artery disease who participated in a 4-week, double-blind, double-dummy, crossover, placebo-controlled trial. After the first week of the placebo phase (single-blinded), all patients received in three different weeks IS-5-MN 20 mg three times daily, gallopamil 50 mg three times daily, and the same dosages of IS-5-MN and gallopamil three times daily. Exercise tolerance, and peak values of heart rate, systolic blood pressure, double product (DP/100), and ST-segment were evaluated with a treadmill test at the end of each phase. The improvement in exercise tolerance obtained by the combination of the two drugs was significantly greater (p < 0.01) than that achieved by IS-5-MN but not that by gallopamil monotherapy (NS). This effect was accompanied by significant (p < 0.05) reduction (-61%) in ST-segment and significant (p < 0.05) increment (+8%) in peak heart rate only after administration of the combination of the two drugs. The number of ST-depression (ST-) > 1 mm or ST-elevation (ST+) episodes on 24-h Holter monitoring lasting > or = 1 min were also noted in all patients at the end of each phase of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Bopindolol in chronic stable angina pectoris: duration and extent of antianginal action.

The effects of bopindolol, a new beta-adrenoceptor blocker, on the exercise tolerance of 12 in-patients, mean age 57 (5 years), with stable angina pectoris and documented coronary artery disease were evaluated. All patients received on 4 different days a single oral dose of bopindolol 0.5 mg, bopindolol 1.0 mg, bopindolol 2.0 mg and placebo according to a double-blind latin square design. Treadmill symptoms-limited exercise tests were performed using a Bruce protocol, 3, 12 and 24 h after dosing. Bipindolol improved (P less than 0.05) exercise tolerance in comparison with placebo (by a maximum of 33%, 52% and 26% after the 2.0 mg dose) with no adverse effect on ischaemia. The primary action of bopindolol appeared to be to reduce myocardial oxygen consumption (mainly by its negative chronotropic effect) for up to the 24th hour after oral administration. Eight (66%) patients were angina free at the 3rd, 12th and 24th h exercise test. The effects of bopindolol were not dose-related. A short period of inactivity due to hospitalization may have influenced the exercise performance and led us to underestimate the presence of a dose-response. The results of this report suggest that bopindolol has a long lasting effect in the treatment of patients with chronic stable angina pectoris.