Thyroid function studies in patients with cancer of the larynx: preliminary evaluation

OBJECTIVE: Our goal was to evaluate thyroid function before and after surgery only or radiotherapy plus surgery for laryngeal neoplasms. STUDY DESIGN AND SETTING: The study group consisted of a total of 30 patients with laryngeal cancer (22 treated with surgery only and 8 treated with surgery plus radiotherapy) who were evaluated by ultrasensitive thyroid-stimulating hormone, free T4, and antithyroid antibodies both preoperatively and at 6 and 12 months after surgery. RESULTS: All patients had normal thyroid function before treatment (1 patient had elevated antithyroid autoantibodies); after 1 year, 4 (13.34%) patients were hypothyroid. In 3 patients, it was subclinical (ie, elevated thyroid-stimulating hormone with normal free T4), and in 1 patient, it was symptomatic. CONCLUSION: Our preliminary data suggest that hypothyroidism occurs in a small but substantial proportion of patients undergoing surgery with or without adjuvant radiotherapy for laryngeal cancer. SIGNIFICANCE: Thyroid hormone dosing should be routinely included in the assessment of patients with laryngeal cancer, because it is simple and inexpensive and may allow the early diagnosis and management of hypothyroidism.     

Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans

BACKGROUND: Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells. OBJECTIVES: The purpose of this study was to investigate the hypothesis that spatial and temporal heterogeneities of restitution underlie the mechanism eliciting discordant alternans. METHODS: Steady-state pacing was used to elicit concordant cellular alternans in nine Langendorff-perfused guinea pig hearts. A single extrastimulus (S2) was applied every 51st beat following either the even or the odd beat of alternans. The cellular response to S2 was determined using optical mapping to generate action potential duration (APD) restitution curves from 256 ventricular sites for both the even and the odd beats. RESULTS: Restitution kinetics were temporally heterogeneous during alternans, as restitution curves between the even and the odd beats differed significantly. Temporal heterogeneity was quantified by the average separation of restitution between the two curves, or Delta-restitution. Delta-Restitution was spatially heterogeneous and proportional to the amount of alternans at a given ventricular site. A computer simulation based on the experimental results showed the mechanism of discordant alternans was dependent on both spatial and temporal heterogeneities of restitution. CONCLUSION: Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Delta-restitution, are proportional to the magnitude of cellular alternans. The combination of spatial and temporal heterogeneities of restitution may underlie the genesis of discordant alternans.     

Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative

OBJECTIVE: To examine the prevalence and correlates of self-reported urogenital symptoms (dryness, irritation or itching, discharge, dysuria) among postmenopausal women aged 50-79. DESIGN: A cross-sectional analysis based on n=98,705 women enrolled in the US-based Women's Health Initiative observational study and clinical trials. Urogenital symptoms, symptom severity (mild, moderate, severe), and all covariates were self-reported through questionnaires at enrollment. Prevalence rates of each urogenital symptom were examined and logistic regression was used to identify potential correlates. RESULTS: Prevalence rates for each symptom were: dryness, 27.0%; irritation or itching, 18.6%; discharge, 11.1%; and dysuria, 5.2%. Four factors were correlated with two or more symptoms: Hispanic ethnicity (adjusted odds ratio (AOR)=2.1-3.1 versus white women across all symptoms), obesity (AOR=2.2 severe discharge versus none, AOR=3.6 severe irritation/itching versus none), treated diabetes (pills or shots) compared to no diabetes (AOR=2.4 severe dysuria versus none, AOR=3.2 severe irritation/itching versus none), and vaginal cream HRT/ERT compared to those who never used HRT/ERT (AOR=4.4 severe dryness versus none, AOR=4.6 severe irritation/itching versus none). Factors not associated with the symptoms included sexual activity, age, years since menopause, current smoking, marital status, gravidity, and natural versus surgical menopause. CONCLUSIONS: This is the first report to document urogenital symptoms by race/ethnicity among an exclusively postmenopausal population. We found an elevated prevalence of urogenital symptoms among women who are Hispanic, obese, and/or diabetic. Confirmation of our findings in these subgroups, and, if confirmed, analysis on why these populations are at greater risk, are areas for future research.     

Evaluation of a Rapid Immunochromatographic Test for Serodiagnosis of Visceral Leishmaniasis

The purpose of this study was to compare the performance of a rapid immunochromatographic dipstick test for the qualitative detection of circulating antibodies to the leishmanial recombinant antigen K39 with that of a classical immunofluorescent antibody test for serodiagnosis of visceral leishmaniasis. Sera from 143 Italian subjects, including 69 patients with clinically suspected visceral leishmaniasis, 23 patients with hypergammaglobulinemia and 51 healthy controls, were tested. The immunochromatographic test was performed according to the manufacturer's instructions, using antigen-impregnated nitrocellulose paper strips. The immunofluorescent antibody test was performed according to an established method, using promastigotes of Leishmania infantum zymodeme Montpellier 1 as antigen. In 11 patients, diagnosis of active Leishmania infection was established by microscopic examination of biopsy samples and/or clinical response to meglumine antimoniate. Results of the two tests correlated for all but two sera examined. In two patients, one with proven infectious mononucleosis and one with bacterial pneumonia, the immunofluorescent antibody test was positive and the dipstick test was negative. In the restricted sample of patients in whom a definitive diagnosis was established, the immunochromatographic test was positive in 11 of 11 patients with confirmed Leishmania infection and negative in 103 of 103 subjects who either had other documented diseases or were healthy controls, showing 100% sensitivity and 100% specificity. Electronic Publication     

Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).     

Distinct delayed T-cell response to beta-methasone and penicillin-G in the same patient

BACKGROUND: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs. Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome. Our aim was to report the case of a delayed reaction to both beta-methasone (beta-MT) and penicillin-G (pen-G) occurring in the same patient, and analyse beta-MT- and pen-G-specific T-cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile. METHODS: We generated two drug-specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T-cell receptor Vbeta (TCR-Vbeta) domains expression and cytokine profile. RESULTS: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen-G and beta-MT through the strict dose-dependent proliferation in response to drug-pulsed autologous antigen presenting cells. Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with beta-MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen-G was found. The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR-Vbeta usage. CD8+ pen-G-TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific beta-MT TCL. CONCLUSION: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and beta-MT, driven, respectively, by pen-G-specificTh2-skewed CD8+ and beta-MT specificTh0 CD4+ T cells. This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity.