Do oral contraceptives improve vocal quality? Limited trial on low-dose formulations

OBJECTIVE: To evaluate the effect of low-dose monophasic oral contraceptives on female vocal quality. METHODS: Acoustic voice parameters of six women who use oral contraceptives and six women who do not were evaluated repeatedly during the menstrual cycle. Frequency and amplitude variations were measured using a computerized voice analysis program. Repeated-measures analysis of variance was performed to test differences between groups for each acoustic voice parameter. RESULTS: Vocal stability among the women who use oral contraceptives was significantly better than among those who did not use oral contraceptives (P <.05). Specifically, amplitude and frequency variations between successive vocal cycles were smaller in women using oral contraceptives in comparison with the control group (.24 dB versus.37 dB and.86% versus 1.27% for amplitude and frequency variations, respectively). CONCLUSION: Contrary to the reports of adverse effects that high-dose pills have on voice, low-dose oral contraceptives show a favorable influence on voice in young women.     

The effect of training on frequency discrimination: generalization to untrained frequencies and to the untrained ear

While there is growing evidence that frequency discrimination improves with practice, there are, however, limited and inclusive reports regarding the generalization of learning to untrained conditions. The goals of the present study were therefore (1) to measure the effect of multi-session training on difference limen frequency (DLF) thresholds and evaluate the relative contribution of procedural and stimulus learning by comparison to a control (untrained) group; (2) to evaluate the extent of generalization of the trained frequency to two untrained frequencies known to be temporally coded; and (3) to estimate the generalization of the trained frequency to the untrained ear, for both trained and untrained frequencies. Two groups of subjects were included: a trained group (n = 5) and a control group (n = 5). For the trained group, DLF thresholds for 1 kHz (trained frequency) and 1.1 and 2.0 kHz (untrained frequencies) were obtained using a two-interval, two-alternative forced choice paradigm before and after an eight-session training. The control group was tested using the same stimuli only twice, with a 3-week interval between testing. Results showed that (1) multi-session training improves frequency discrimination in normal hearing young adults; (2) adding a control group to the study allowed estimation of the effect of limited exposure to the stimuli and task in na?ve listeners and evaluation of the magnitude of procedural learning; (3) learning was generalized across frequencies that are coded by similar mechanisms; (4) generalization of learning occurred in the untrained ear for trained and untrained frequencies. These results have important clinical and theoretical implications regarding the processes underlying perceptual learning and the effectiveness of auditory habilitation strategies.     

Effect of second-formant transitions on the perception of Hebrew voiced stop consonants

Studies in English, Dutch, Danish and French show that of the possible acoustic cues that listeners use for the perception of place of articulation, the transition of the second formant (F2) appears to be a very important cue. Although the Hebrew language shares some similarities with the above languages, one cannot assume that it either has similar acoustic-articulatory patterns or uses the same cues for perception. The general goal of the present study was, therefore, to investigate the effect of the starting frequency of F2 transition on the perception of place of articulation of Hebrew voiced plosives in initial position. Sixteen Hebrew-speaking young normal-hearing adults served as subjects. Stimuli were generated by re-synthesizing a naturally spoken /ba/ syllable into 17 test syllables by varying only the starting frequency of F2. Listeners heard each stimulus six times (total of 102) at random and were required to label the stimuli as /ba/, /da/ or /ga/. Results showed that varying only F2 transitions caused a perceptual change of place of articulation for all listeners. There was, however, large inter-subject variability in the perceived category: 75% of the subjects identified /ba/ and /da/, half of them also identified /ga/, and 25% of the subjects were able to identify /ba/ and /ga/ only. These data suggest that while F2 transitions are important for perceiving place of articulation of Hebrew voiced stops, they cannot predict the perceived category. It also supports the notion that normal-hearing listeners differ in the relative importance they assign to the cues for the perception of place of articulation.     

Primary non-Hodgkin’s lymphoma of the transverse colon presenting as dermatomyositis

Primary extranodal non-Hodgkin’s lymphoma of the transverse colon is a rare presentation of non-Hodgkin’s lymphoma or colonic neoplasm. Dermatomyositis is an autoimmune condition of the skin, muscle, and blood vessels that when associated with malignancy is a true paraneoplastic syndrome but is rarely associated with non-Hodgkin’s lymphoma. We present a case of primary non-Hodgkin’s lymphoma of the transverse colon diagnosed after the presentation of dermatomyositis and review the literature on dermatomyositis and hematologic neoplasm.     

Three‐Dimensional Ultrasonography of the Fetal Vermis at 18 to 26 Weeks' Gestation

Objective. The purpose of this study was to establish the normality of the fetal vermis, ie, the time of appearance of the primary fissure, as well as its measurements between 18 and 26 weeks' gestation, using 3‐dimensional (3D) ultrasonography. Methods. A prospective cross‐sectional study of normal singleton pregnancies was conducted. Examinations were performed with high‐resolution transabdominal ultrasonography using the axial plane in 173 fetuses between 18 and 26 weeks' gestation. Postprocessing measurements of the fetal vermis were done with 4‐dimensional software using static volume contrast imaging and tomographic ultrasound imaging in the C‐plane. Detection of the primary fissure was evaluated in all cases, and the time of appearance was documented. Results. Adequate vermis measurements were obtained in 173 fetuses. Vermian length as a function of gestational age was expressed by regression equations, and the correlation coefficients were found to be highly statistically significant (P < .001). The normal mean ± 2 SD for each gestational week was defined. The primary fissure was observed at 24 weeks' gestation in all cases, at 22 weeks in 94% of cases, and as early as 18 weeks in 40%. Conclusions. This 3D study documents the appearance of the primary fissure and presents the normal range of vermian measurements, confirming normal development of the fetal vermis starting as early as 18 weeks' gestation. It also shows an easy method for visualizing the vermis with 3D ultrasonography at every gestational week regardless of fetal presentation.     

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Ovarian cancer is the eighth most common cancer and cancer death in women worldwide (1). High-grade serous tubo-ovarian cancer (HGSC) constitutes ∼70% of all ovarian malignancies and has the worst prognosis (2). Current treatment of most patients with HGSC consists of cytoreductive surgery and combination chemotherapy with platinum-containing DNA–cross-linking drugs and taxane-based microtubule-stabilizing agents (2). Although treatment significantly improves survival, most women relapse with chemotherapy-refractory disease and eventually succumb (3). Multiple mechanisms of chemoresistance have been documented (4, 5), including reduced intracellular drug accumulation (6), detoxification by increased levels of glutathione (7), altered DNA damage repair (8, 9), dysfunctional apoptotic pathways (10, 11), and hyperactivation of various cell signaling pathways (12–14). These mechanistic studies are consistent with recent genomic analyses that reveal marked clonal evolution of HGSC during therapy (15). Other evidence, however, supports a hierarchical organization of HGSC, featuring intrinsically chemoresistant “cancer stem cells” (CSCs) that can escape initial treatment and seed recurrence (16–18).Although there is uniform agreement that HGSC patients should receive surgery and chemotherapy, the optimal order and timing of these modalities remain controversial. Two main options exist: primary debulking surgery with adjuvant chemotherapy (PDS), or neoadjuvant chemotherapy, followed by interval debulking surgery (NACT) (19–24). In either case, the surgical standard of care is to seek maximal cytoreduction, with the objective being to leave no visible residual disease. However, the precise definition of such “optimal debulking” can vary among different centers, surgeons, and reports (19, 21, 24, 25).Several studies have found similar outcomes after PDS or NACT, including two highly influential randomized trials (EORTC and CHORUS) carried out across multiple countries (22, 23, 26–28). In both trials, however, the question of potential bias in patient recruitment has been raised, favoring potentially those with more extensive disease, who are less likely benefit from “upfront” surgery (23, 28). Consistent with this interpretation, overall survival in these trials was significantly shorter than that seen in other HGSC cohorts (19, 24, 29, 30). Closer examination of these reports reveals additional factors that might have influenced their conclusions. The EORTC study had inconsistencies in optimal debulking rates between participating centers, with the PDS-associated complete debulking data highly influenced by the results from a single institution (23). The CHORUS study involved 76 clinical sites, and there were substantial differences in surgery execution and chemotherapy drug selection/dosage between them (28).At Princess Margaret Cancer Center, retrospective data showed that PDS patients with no visible disease postresection survived substantially longer (7-y survival, >60%) than those receiving NACT (7-y survival, ∼10%). Furthermore, although residual tumor postresection is a critical determinant of survival, its influence on the PDS group was far more dramatic than on NACT group (24). Of course, this report suffers from deficiencies common to all retrospective analyses, including lack of randomization to account for tumor burden at diagnosis and other factors; indeed, the NACT group in this study did have more extensive disease.Another controversy in HGSC management focuses on the potential benefit of earlier diagnosis. Earlier diagnosis of primary HGSC is generally assumed to enhance patient survival and quality of life (3). Intuitively, one might predict that the same reasoning would apply to recurrent disease; however, survival is similar in relapsed patients treated earlier, based on increasing serum CA125 levels, than in those treated only when physical symptoms of recurrence appear (31). Conceivably, the lead time between CA125 rise and clinical recurrence is too short for earlier chemotherapy to be beneficial; if so, then patient survival might be extended by more sensitive methods, such as testing for circulating tumor DNA (ctDNA) (32, 33).To address these issues, we developed a mathematical framework that models the dynamics of HGSC progression, response to surgery and chemotherapy, and recurrence. Our results, generated over a wide range of parameters and accounting for hierarchical and stochastic models of tumor initiation, argue that PDS is superior to NACT when complete debulking is feasible and suggest that, with currently available therapies, the benefits of earlier detection are intrinsically restricted to primary HGSC.     

The experience of Black consumers in the mental health system--identifying barriers to and facilitators of mental health treatment using the consumers' perspective

Research has shown that relative to Whites, Blacks are less likely to seek outpatient mental health treatment and more likely to seek emergency services. Furthermore, Blacks often terminate treatment prematurely. The goal of the present study was to identify barriers to and facilitators of mental heath treatment among Blacks who have a documented need for mental health services. Thirty-four Black mental health consumers were interviewed for this purpose. Comments were categorized into four main categories: (a) barriers to treatment, (b) treatment facilitators, (c) recommendations for improvement of services, and (d) advice to potential consumers. The most common barriers were the importance of family privacy, lack of knowledge regarding available treatments, denial of mental health problems, and concerns about stigma, medications, and treatment. Participants also reported system barriers, such as not receiving appropriate information about services or receiving inadequate, dehumanizing services. Acknowledging the need for mental health services, having a supportive environment, and positive past treatment experiences were identified as treatment facilitators. Community outreach, adequate follow-up, and coordination of services also were important messages delivered by consumers. The results of this study indicate the importance of educating the general public, not just mental health consumers, about the nature of mental illness and available services.     

Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials

OBJECTIVES: This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection. METHODS: Systematic review of the literature and meta-analysis. We searched for randomized controlled trials comparing the efficacy of single aminoglycoside antibiotic treatment with one or more non-aminoglycoside antibiotic for patients with infection in the Cochrane Library, MEDLINE, EMBASE, LILACS, databases of ongoing trials and conference proceedings. Two reviewers assessed trial eligibility, quality and extracted data. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. RESULTS: The search yielded 37 trials of which 26 included patients with urinary tract infection. Aminoglycosides were equally effective as comparators in the analysis of the primary outcomes, all-cause mortality (RR 1.11, 95% CI 0.68, 1.81, 9 trials, 503 patients) and treatment failure (RR 1.10, 95% CI 0.96, 1.27, 32 trials, 1890 patients). Aminoglycosides were associated with a significantly higher rate of bacteriological failure at end of therapy (RR 1.44, 95% CI 1.21, 1.72, 27 trials, 1668 patients). Subgroup analyses according to quality of trial, type of antibiotics, source of infection and rate of clinical sepsis did not alter the outcomes. Less adverse effects in total but more nephrotoxic effects were observed in patients treated with aminoglycosides. CONCLUSIONS: The present data support the use of aminoglycosides for urinary tract infections. The paucity of trials including patients with sepsis or reporting on mortality precludes firm recommendations for patients with infections other than of the urinary tract.     

Kaposi's sarcoma-associated herpesvirus: clinical, diagnostic, and epidemiological aspects

Kaposi's sarcoma-associated herpesvirus (KSHI) is one of the few viruses proven to be associated with tumorigenesis in humans. Its causal association with all clinical and epidemiological variants of Kaposi's sarcoma (KS) is well established. KSHV is also involved in the pathogenesis of primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease (MCD). Possible associations of KSHV with other clinical settings have been extensively examined. The findings from several of these studies are contradictory and are yet to be resolved. Concentrated effort over the last decade, since the initial discovery of KSHV, led to the development of several experimental systems that resulted in a better comprehension of the biological characteristics of KSHV and set the stage for the understanding of mechainisms by which diseases are induced by the virus. The development of molecular, histological, and serological tools for KSHV diagnosis allowed researchers to track the transmission and to study the epidemiology of KSHV. These assays have been applied, in particular in ambiguous cases, in order to confirm clinically and pathologically based diagnoses. Here, we review the advances in the clinical, experimental, diagnostic, and epidemiological research of KSHV.