Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts.

Optogenetics enables cell-type specific monitoring and actuation via light-activated proteins. In cardiac research, expressing light-activated depolarising ion channels in cardiomyocytes allows optical pacing and defibrillation. Previous studies largely relied on epicardial illumination. Light penetration through the myocardium is however problematic when moving to larger animals and humans. To overcome this limitation, we assessed the utility of an implantable multi light-emitting diode (LED) optical probe (IMLOP) for intramural pacing of mouse hearts expressing cardiac-specific channelrhodopsin-2 (ChR2). Here we demonstrated that IMLOP insertion needs approximately 20 mN of force, limiting possible damage from excessive loads applied during implantation. Histological sections confirmed the confined nature of tissue damage during acute use. The temperature change of the surrounding tissue was below 1 K during LED operation, rendering the probe safe for use in situ. This was confirmed in control experiments where no effect on cardiac action potential conduction was observed even when using stimulation parameters twenty-fold greater than required for pacing. In situ experiments on ChR2-expressing mouse hearts demonstrated that optical stimulation is possible with light intensities as low as 700 µW/mm2; although stable pacing requires higher intensities. When pacing with a single LED, rheobase and chronaxie values were 13.3 mW/mm2 ± 0.9 mW/mm2 and 3 ms ± 0.6 ms, respectively. When doubling the stimulated volume the rheobase decreased significantly (6.5 mW/mm2 ± 0.9 mW/mm2). We have demonstrated IMLOP-based intramural optical pacing of the heart. Probes cause locally constrained tissue damage in the acute setting and require low light intensities for pacing. Further development is necessary to assess effects of chronic implantation.

Urinary incontinence in primigravida: the neglected pregnancy predicament.

OBJECTIVE: To determine the prevalence of urinary incontinence among primigravida in the third trimester, its risk factors and its effect to quality of life. STUDY DESIGN: This is a cross sectional study involving primigravida in their third trimester of pregnancy, who attended the Patient Assessment Centre of a tertiary referral hospital in Klang Valley from July 2012 to June 2013. The participants were chosen randomly using convenience sampling. A face-to-face interview and a review of their antenatal record were done by trained interviewers. Data on sociodemographic and risk factors were obtained followed by the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF). The data was analysed using Statistical Package for Social Science version 20.0. RESULTS: A total of 306 women were involved. The prevalence of urinary incontinence during third trimester was 34.3% (95%CI: 29.0, 39.7). Stress incontinence (64.8%) is the commonest followed by mixed incontinence (24.8%) and urge incontinence (6.7%). Childhood enuresis (p=0.003) and previous history of urinary incontinence (p<0.001) were significantly associated with urinary incontinence. More than 50 percent of women with urinary incontinence in the third trimester felt that it did not affect their daily activities at all. Only 10% of women felt greatly affected by this problem. CONCLUSION: Urinary incontinence is not uncommon among primigravida however many women did not feel that it affected their quality of life. Childhood enuresis and history of urinary incontinence were proven risk factors.

Mediastinal mass diagnosed as a benign schwannoma.

Neurogenic tumours of the mediastinum are most commonly present in the posterior mediastinal compartment. Schwannomas, being the most frequently encountered type, can be either benign or malignant, although the former is more common. They typically appear as an asymptomatic mass on radiographic imaging. These tumours with spindle-shaped cells are often asymptomatic, and are routinely detected on standard pulmonary radiography. However, computed tomography and magnetic resonance imaging, especially for posterior mediastinal tumours, provide additional information and help to determine its possible extension to adjacent structures. Therefore, radiographic and histopathological examinations are vital diagnostic tools in the detection of these silent tumours. Complete surgical resection using video-assisted thoracic surgical technique is the mainstay of treatment, and offers an excellent prognosis.

Accuracy of VA databases for diagnoses of knee replacement and hip replacement.

PURPOSE: To examine the validity of International Classification of Diseases-Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) codes for knee replacement and hip replacement in Veterans Affairs (VA) databases. METHODS: From a cohort of veterans who received health care at Minneapolis VA Medical Center and/or affiliated medical facilities, we obtained four random samples of 50 patients each with: neither hip nor knee replacement code, knee replacement code only, hip replacement code only and both knee and hip replacement codes. The gold standard was documentation of knee or hip replacement surgery in patient medical records. Accuracy of ICD-9 or CPT code for knee and hip replacement was assessed by calculating sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Of the 200 patients, medical records were available for 166:140 (70%) had complete medical records and 26 (13%) had incomplete medical records. Knee replacement codes were accurate with excellent PPV of 95%, sensitivity of 95%, specificity of 96% and NPV of 96%. Hip replacement codes were accurate with excellent PPV of 98%, sensitivity of 96%, specificity of 99% and NPV of 96%. Sensitivity analyses that included incomplete charts had little impact on these estimates. The procedure dates found in VA databases matched exactly with medical records in 96%. CONCLUSIONS: The ICD-9 and CPT codes for knee replacement and hip replacement in VA databases are valid. These codes may be used to identify cohorts of veterans with knee replacement and hip replacement for research studies.

The epidemiology of hospitalization with diarrhea in rural Kenya: the utility of existing health facility data in developing countries.

OBJECTIVES: In developing countries where prospective surveillance is resource-intensive, existing hospital data can define incidence, mortality, and risk factors that can help target interventions and track trends in disease burden. METHODS: We reviewed hospitalizations from 2001 to 2003 at all inpatient facilities in Bondo District, Kenya. RESULTS: Diarrhea was responsible for 11.2% (n=2158) of hospitalizations. The annual incidence was 550 and 216 per 100,000 persons aged <5 and > or =5 years, respectively. The incidence was highest in infants (1138 per 100,000 persons), decreased in older children, peaked again among 20-29-year-olds (341 per 100,000), and declined among those > or =65 years (157 per 100,000). Female adults had higher incidence than males (rate ratio=1.84, 95% CI 1.61-2.10). Incidence decreased with distance from the district referral hospital (4.5% per kilometer, p<0.0001) and from the nearest inpatient facility (6.6% per kilometer, p=0.012). Case-fatality was high (8.0%), and was higher among adults than young children. Co-diagnosis with malaria, pneumonia, HIV, and tuberculosis was common. Peak diarrhea incidence fell one to two months after heavy rains. CONCLUSIONS: The trends revealed here provide useful data for public health priority setting and planning, including preventative interventions. The utility of such data justifies renewed efforts to establish and strengthen health management information systems in developing countries.

The epidemiology of hospitalized pneumonia in rural Kenya: the potential of surveillance data in setting public health priorities.

INTRODUCTION: Surveillance data from inpatient health facilities can be useful for prioritization of public health initiatives, but often are not collected or analyzed in developing countries. We evaluated data on hospitalized patients diagnosed with pneumonia in rural western Kenya to characterize pneumonia epidemiology and mortality. METHODS: Data were obtained from admission registers of all inpatient facilities from 2001 to 2003 in Bondo District (estimated 2003 population: 255901), which is holoendemic for malaria and has high HIV rates. Inpatients with diagnoses compatible with acute pneumonia were included, and census data (1999) were used to calculate incidence rates by age, sex, season, and residence. RESULTS: From 2001 to 2003, a total of 2466 patients diagnosed with pneumonia were hospitalized with 282 deaths (11.4%). Incidence peaked at 698 per 100,000 person-years among children <5 years of age. A second peak occurred among 20-29 year-olds at 356 per 100,000 person-years; rates were twice as high in women as men in this age group (p<0.001). The incidence in persons >65 years was 121 per 100,000 person-years. Pneumonia incidence peaked during the twice-yearly high malaria seasons, 1-2 months after peak rainfall. Rates of pneumonia decreased with increasing distance of residence from the district hospital (p<0.0001). DISCUSSION: In Bondo District, the pneumonia burden is greatest among young children and middle-aged adults, the latter peak reflecting the area's HIV epidemic. Access to care likely influenced hospital utilization and thus pneumonia rates, particularly among the elderly. Our findings show that hospital-based data can provide useful information for public health priority setting, such as the introduction of new pneumonia vaccines for children and accelerating the introduction of antiretroviral medications.

Cutaneous leishmaniasis in Multan: species identification.

OBJECTIVE: To identify the Leishmania species being responsible for cutaneous leishmaniasis in Multan. METHOD: Parasites were isolated from clinically and parasitologically confirmed lesions of cutaneous leishmaniasis from 30 patients by fine needle aspiration (FNA). The bioptical materials were then cultured in Evans Tobie's medium and parasites isolated were identified by isoenzyme electrophoresis technique. RESULTS: Successful Leishmania isolates were obtained from 16 patients. All strains were identified by biochemical techniques as belonging to Leishmania tropica zimodeme MON7 variant PGD. CONCLUSION: The causative species was identified as Leishmania tropica.

Genetic and structural polymorphism of complement receptor 1 in normal Indian subjects.

The human complement receptor 1 (C3b/C4b receptor, CD35, CR1), a polymorphic membrane bound glycoprotein, is differentially expressed on erythrocytes, eosinophils, monocytes, B and T-lymphocytes, dendritic cells and kidney podocytes. It also occurs in the plasma as soluble CR1 (sCR1) and in urine as urinary CR1 (uCR1). Different population studies have suggested the functional and physiological significance of the structural (CR1-A/190, CR1-B/220, CR1-C/160 and CR1-D/250 kDa) and genomic (HH, high erythrocyte CR1 expression, HL, intermediate and LL, low expression) polymorphisms in health and disease. However, simultaneous study on the structural and genomic polymorphism in the same group of study subjects is lacking. This is the first study on both quantitative and structural polymorphism in 101 healthy volunteers from different parts of India by random sampling. In our study, AA phenotype was found to be expressed in 84.2% of individuals and 14.8% carried AB phenotype. One individual (0.9%) was found to possess BB phenotype. Homozygous BB pattern was identified for the first time in Indian subjects. The relative gene frequencies for A and B allele were found to be 0.916 and 0.084, respectively. Pertaining to quantitative polymorphism, percentage distribution for HH, HL and LL phenotypes was found to be 23.7, 54.45 and 21.79%, respectively and the gene frequencies were 0.51 and 0.49 for H and L allele, respectively. The observations for quantitative as well as structural polymorphism showed a good probability of fitness with Hardy-Weinberg equilibrium, thus proving that both the types of CR1 polymorphic forms are encoded by autosomal co-dominant alleles. We found a higher frequency of HL and AA phenotypes in the study subjects. Our findings are unique as we found that gene frequencies for structural and quantitative polymorphism in our study subjects were a combination of those found in Caucasian and Oriental populations.

The utilization of services of health care providers among patients presenting to family physicians at a teaching hospital in Karachi, Pakistan.

OBJECTIVE: To study the utilization of services of Health care providers among patients presenting to Family Physicians in a teaching hospital in Karachi. METHODOLOGY: It was a cross sectional study. A questionnaire was developed to collect patient's utilization of services of health care providers. The investigators administered the questionnaire to 387 patients, after purpose of the study was explained, written consent was taken and confidentiality was assured. RESULTS: The study population included more females than males, with average age of 32.6 years. The majority were married, well educated, in private and government service, were students or housewives. We found that 383(99%), 141(36.4%), 88(22.7%) and 45(11.6%) of the respondents had used services of allopaths, homeopaths, hakims and spiritual healers respectively. It is important to consider that these patients had come for allopathic treatment, thus exhibiting preference for it. The five main ailments for consulting health care providers differed, suggesting the perception in the mind of patients that certain ailments are better treated by particular system of treatment than the others. Studies are needed to explore this area further. The main reasons for consultation with particular health care provider were the recommendation of others or the perceived effectiveness of the practitioners. The reasons cited for non-consultation with health care providers were the lack of belief in them or lack of effectiveness of their treatment. Three hundred seventy nine (98%), 259 (67%), 174 (45%) and 249 (64.4%) of patients were willing to consult allopaths, homeopaths, hakims and spiritual healers again respectively, if unwell in future. CONCLUSION: We found a substantial utilization of services of complimentary medicine practitioners among patients seeking allopathic treatment. Further study on the utilization and organization of services offered by health care providers is required.

Profile of patients of cutaneous leishmaniasis from Multan.

OBJECTIVE: Cutaneous leishmaniasis is endemic in Multan. Therefore this study was undertaken to elucidate the epidemiological features with main emphasis on the geographical distribution of the infection in Multan. SETTINGS: Multan city. Dermatology Outpatient Department, Nishtar Medical College. METHOD: Records of 173 diagnosed patients of cutaneous leishmaniasis were retrospectively reviewed according to the age, sex, number and site of lesions, results of the smear for LD bodies and residential area. RESULTS: The disease was more common in the children and young adults, with male to female ratio of 3:2. The maximum number of lesions were on the lower legs. Sixty five percent of the patients were from the interior old city. CONCLUSION: The main focus of infection is in old interior part of the city with microfoci of the disease scattered throughout the city.

Validation of an ELISA for the quantitation of human complement receptor 1.

An ELISA was developed and validated for the quantitation of Complement Receptor 1 (CR1) in human plasma. The ELISA employed a monoclonal anti-CR1 antibody adsorbed onto microtiter plates to capture CR1 in human plasma. The captured CR1 was treated with a detecting antibody which had a different epitopic specificity for CR1. HRP conjugated anti IgG (secondary antibody) was used for quantitation. The standard curve covered a wide range from 10 pg to 800 pg. The inter- and intra-assay variation were found to be low and within the acceptable limits. Specificity and accuracy for the assay was established by ensuring negligible cross reactivity with other proteins and an excellent parallelism between the sample and standard curve. The samples were checked for loss of sCR1 levels through freeze/thaw cycles at different intervals of time stored at -70 degrees C.

Effect of disintegrants and hardness on the disintegration time of Acetaminophen tablets.

In this study the effect of various disintegrates on the disintegration time of laboratory prepared Acetaminophen tablets at different hardness has been determined. The disintegration time was found to be directly related with the hardness of the tablets for all formulations studied except in tablets containing veegum.