The oral mucosa as a therapeutic target for xerostomia

Autoimmune disorders, medical interventions, and aging are all known to be associated with salivary gland hypofunction, which results in the uncomfortable feeling of dry mouth (xerostomia) and significantly diminished oral health. The current therapeutic regimen includes increasing oral hydration using over‐the‐counter oral comfort agents and the use of systemic cholinergic drugs to stimulate salivary output. However, these approaches produce very transient relief or are associated with uncomfortable side‐effects. Thus, new treatments that provide long‐lasting relief from discomfort and improve oral health with minimal side‐effects would benefit the therapy of this disease. The processes that mediate fluid loss from the oral cavity, such as the absorption of fluid from the oral mucosa, represent novel therapeutic targets for xerostomia. Preventing fluid absorption from the oral cavity is predicted to improve oral hydration and alleviate the clinical symptoms and discomfort associated with dry mouth. Furthermore, therapeutic strategies that prevent fluid absorption should complement current approaches that increase salivary output. This review discusses the current understanding of oral fluid balance and how these processes may be manipulated to provide relief for those suffering from dry mouth.     

Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits [published erratum appears in Hum Mol Genet 1998 Apr;7(4):765]

A subtype of neuronal ceroid lipofuscinosis (NCL) is well recognized which has a clinical course consistent with juvenile NCL (JNCL) but the ultrastructural characteristics of infantile NCL (INCL): granular osmiophilic deposits (GROD). Evidence supporting linkage of this phenotype, designated vJNCL/GROD, to the INCL region of chromosome 1p32 was demonstrated (pairwise lod score with D1S211 , Z max = 2.63, straight theta = 0.00). The INCL gene, palmitoyl-protein thioesterase (PPT ; CLN1), was therefore screened for mutations in 11 vJNCL/GROD families. Five mutations in the PPT gene were identified: three missense mutations, Thr75Pro, Asp79Gly, Leu219Gln, and two nonsense mutations, Leu10STOP and Arg151STOP. The missense mutation Thr75Pro accounted for nine of the 22 disease chromosomes analysed and the nonsense mutation Arg151STOP for seven. Nine out of 11 patients were shown to combine a missense mutation on one disease chromosome with a nonsense mutation on the other. Mutations previously identified in INCL were not observed in vJNCL/GROD families. Thioesterase activity in peripheral blood lymphoblast cells was found to be markedly reduced in vJNCL/GROD patients compared with controls. These results demonstrate that this subtype of JNCL is allelic to INCL and further emphasize the correlation which exists between genetic basis and ultrastructural changes in the NCLs.      

STUDY ON INTEROBSERVER AGREEMENT IN A GOITRE PREVALENCE SURVEY

Observers differ in their judgment while assessing physical signs in a patient. We had undertaken a goitre prevalence survey amongst school students in a Rural Health Training Centre, Pune district (Maharashtra) during October 1992. Four teams of trained observers were used for detection of goitre. This study was undertaken to estimate the extent and acceptability of interobserver agreement amongst the four teams. Observer variation/agreement was measured by two methods viz. kappa coefficient and proportion of agreement. The proportion of agreement appears to be a better measure of observer agreement as it could make a distinction between normality (absence of goitre) and abnormality (presence of goitre). In the present study, the proportion of agreement for abnormality ranged between 0.62 – 0.83. This measure was considered as indicating a good interobserver agreement in detecting goitre in the survey that was undertaken.KEY WORDS: Confidence intervals, Epidemiologic methods, Health surveys, Observer variation     

Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors

We discovered a high-level amplicon involving the ehrl9ql3.41 microRNA （miRNA） duster （C19MC） in 11/45 （approximately 25%） primary CNS-PNET, which results in striking overexpression of nfiR-517c and 520g. Constitutive expression of miR-517c or 520g protnotes in vitro and in vivo oncogenicity, modulates cell survival, and robustly enhances growth of untransformed human neural stem cells （hNSCs） in part by upregulating WNT pathway signaling and restricting differentiation of hNSCs.     

Experience converting an RT department to full CT simulation: Technical issues identified during commissioning of a wide‐bore scanner

The advent of CT scanners with larger bore sizes have offered the potential for radiotherapy departments to undertake the majority or all treatment planning simulation via CT. Wide‐bore scanners can present some unique issues when being commissioned for clinical use. During the process of converting a radiotherapy department to full CT simulation, several issues regarding images produced by a wide‐bore scanner were identified. These were investigated by using electron density and image resolution phantoms. It was found that the reconstruction algorithm used by the scanner of interest for extended field of view (FOV) imaging, combined with the extended X‐ray source‐to‐detector distance, influenced the resolution and quality of images. The reconstruction technique influenced the relationship between electron density and CT number with distance from the scanner axis, leading to image artefacts. A variation of 400 CT units is seen for cortical bone across the scanner FOV, with smaller variations for water and breast tissue. It is anticipated that this variation will impact on tissue delineation, and subsequent dose calculation would become questionable should beams pass through large areas of artefact. Image resolutions of 0.5 and 0.3 line‐pairs per millimetre (lp/mm) were achievable in the primary and extended FOV regions respectively. Several aspects of image production with a wide‐bore scanner that can influence imaging for radiotherapy treatment planning have been highlighted. Departments should be mindful of these issues when using a GE Lightspeed wide‐bore scanner and should consider how scanner settings should be optimised for the use of images in treatment planning.     

The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes' VO2max, aerobic, and anaerobic thresholds in normoxia

Whereas experimental studies showed that in healthy trained subjects, the phosphodiesterase-5 inhibitor (PDE-5i) sildenafil improves exercise capacity in hypoxia and not in normoxia, no studies on the effects of the long half-life PDE-5i tadalafil exist. In order to evaluate whether tadalafil influences functional parameters and performance during a maximal exercise test in normoxia, we studied 14 healthy male athletes in a double-blind cross-over protocol. Each athlete performed two tests on a cycle ergometer, both after placebo or tadalafil (at therapeutic dose: 20 mg) administration. Oxygen consumption (VO2), blood lactate, respiratory exchange ratio, rate of perceived exertion, arterial blood pressure (BP), heart frequency (HR) and oxygen pulse (VO2/HR) were evaluated before exercise, at individual ventilatory and anaerobic thresholds (IVT and IAT), at VO2max and during recovery. Compared to placebo, a single tadalafil administration significantly reduced systolic BP before and after exercise (p < 0.05), decreased VO2/HR at IVT (13.3 +/- 1.8 vs. 14.5 +/- 2.1 mL . beat (-1); p = 0.03), but did not modify individual VO2max, IVT, or IAT. In healthy athletes, 20 mg of tadalafil does not substantially influence physical fitness-related parameters, exercise tolerance, and cardiopulmonary responses to maximal exercise in normoxia; it remains to be verified if higher doses/prolonged use influence health and/or sport performance in field conditions.     

HIV,highly active antiretroviral therapy and the heart: a cellular to epidemiological review

The advent of potent highly active antiretroviral therapy (HAART) for persons infected with HIV‐1 has led to a “new” chronic disease with complications including cardiovascular disease (CVD). CVD is a significant cause of morbidity and mortality in persons with HIV infection. In addition to traditional risk factors such as smoking, hypertension, insulin resistance and dyslipidaemia, infection with HIV is an independent risk factor for CVD. This review summarizes: (1) the vascular and nonvascular cardiac manifestations of HIV infection; (2) cardiometabolic effects of HAART; (3) atherosclerotic cardiovascular disease (ASCVD) risk assessment, prevention and treatment in persons with HIV‐1 infection.     

An Evaluation of Coverage and Compliance of Mass Drug Administration 2006 for Elimination of Lymphatic Filariasis in Endemic Areas of Gujarat

Background:

Mass drug administration (MDA) means once-in-a-year administration of diethyl carbamazine (DEC) tablet to all people (excluding children under 2 years, pregnant women and severely ill persons) in identified endemic areas. It aims at cessation of transmission of lymphatic filariasis.

Objective:

What has been the coverage and compliance of MDA in Gujarat during the campaign in December 2006?

Study Design:

Cross-sectional population based house-to-house visit.

Setting:

Urban and rural areas in Gujarat identified as endemic for filariasis where MDA 2006 was undertaken.

Study Variables:

Exploratory - Rural and urban districts; Outcome - coverage, compliance, actual coverage, side effects.

Analysis:

Percentage and proportions.

Results:

Twenty-six clusters, each comprising 32 households from six endemic districts, yielded an eligible population of 4164. The coverage rate was 85.2% with variation across different areas. The compliance with drug ingestion was 89% with a gap of 11% to be targeted by intensive IEC. The effective coverage (75.8%) was much below the target (85%). Side effects of DEC were minimum, transient and drug-specific. Overall coverage was marginally better in rural areas. The causes of poor coverage and compliance have been discussed and relevant suggestions have been made.     

Nasal histoplasmosis in the acquired immunodeficiency syndrome

Disseminated histoplasmosis is a disease with a high case-fatality rate, especially in patients with the acquired immunodeficiency syndrome (AIDS). The disease can occur in various sites, such as the lungs, eyes, oral cavity, larynx, nervous system, gastrointestinal tract and, more rarely, the nasal sinus region. It is a cosmopolitan mycosis with a high prevalence in Brazil. Nasal manifestation of the disease is rare, with only three cases reported in the literature, but it is part of the differential diagnosis for other granulomatous diseases, such as Wegener's granulomatosis, tegumentary leishmaniasis and nasal lymphoma. The authors of this study present a literature review and report a case of nasal histoplasmosis in a patient with AIDS. No record of such an aggressive presentation has been reported previously in the literature.     

复发性口疮患者静止期与溃疡期T抑制细胞功能比较研究

目的 :本研究旨在比较RAU患者溃疡期和静止期外周血淋巴细胞抑制活性 ,探索T抑制细胞在RAU发病学中的作用。方法 :应用刀豆碱 (ConA)激活产生的淋巴细胞抑制检测方法探测了 12位RAU患者溃疡期和静止期外周血淋巴细胞抑制活性。结果 :溃疡期患者的T淋巴细胞抑制率明显低于正常组 (P <0 .0 5 ) ;而患者静止期的抑制率与正常组无显著性差异 (P >0 .0 5 )。结论 :RAU患者外周血T抑制细胞功能在溃疡期降低 ,但对其病损的发展无明显作用