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A substantial dropout from the first dose of diphtheria-tetanus-pertussis (DTP1) to the 3rd dose of DTP (DTP3) immunization has been recorded in Pakistan. We conducted a randomized controlled trial to assess the effects of providing a substantially redesigned immunization card, centre-based education, or both interventions together on DTP3 completion at six rural expanded programme on immunization (EPI) centres in Pakistan. Mother-child pairs were enrolled at DTP1 and randomized to four study groups: redesigned card, centre-based education, combined intervention and standard care. Each child was followed up for 90 days to record the dates of DTP2 and DTP3 visits. The study outcome was DTP3 completion by the end of follow-up period in each study group. We enrolled 378 mother-child pairs in redesigned card group, 376 in centre-based education group, 374 in combined intervention group and 378 in standard care group. By the end of follow-up, 39% of children in standard care group completed DTP3. Compared to this, a significantly higher proportion of children completed DTP3 in redesigned card group (66%) (crude risk ratio [RR] = 1.7; 95% CI = 1.5, 2.0), centre-based education group (61%) (RR = 1.5; 95% CI = 1.3, 1.8) and combined intervention group (67%) (RR = 1.7; 95% CI = 1.4, 2.0). Improved immunization card alone, education to mothers alone, or both together were all effective in increasing follow-up immunization visits. The study underscores the potential of study interventions' public health impact and necessitates their evaluation for complete EPI schedule at a large scale in the EPI system. [ABSTRACT FROM AUTHOR]

Objective In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria–tetanus–pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan. Method We analyzed a cohort of mother–child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrolment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion. Results Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrolment in multivariable analysis, DTP3 completion was higher among children who were ≤60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06–1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16–2.65), and who were living ≤10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04–1.66). Conclusions Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts. Objectivo: Identificar los factores que predicen el completar la DTP3 entre niños que han recibido DTP1 en seis centros del Programa Ampliado de Inmunización (PAI) en áreas rurales de Pakistán. Método: Estudio de cohortes de pares madre-hijo que recibieron DTP1 entre Noviembre 2005 y Mayo 2006 dentro del grupo de cuidados estándar de un ensayo aleatorizado y controlado más grande. Los datos fueron recolectados de las madres mediante un cuestionario estructurado en el momento de la inclusión en el estudio, y cada niño fue seguido mediante visitas clínicas durante 90 días para tomar datos de las fechas en las que recibieron DTP2 y DTP3. Se realizó un análisis de regresión binomial-logística múltiple para identificar vaticinadores independientes de completar DTP3. Resultados: Solo 39% (149/378) de los niños incluidos en el estudio completaron DTP3 durante el periodo de seguimiento. Después de ajustar para el centro de inclusión en un análisis multivariable, el haber completado DTP3 fue mayor entre los niños que eran ≤60 días en el momento de incluirles en el estudio (tasa de riesgo ajustada [Adj. RR] 1.39, 95% intervalo de confianza [IC]: 1.06-1.82), que vivían en una casa con un ingreso mensual >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16-2.65), y que vivían a ≤ 10 minutos del centro de PAI (Adj. RR 1.31, 95% IC: 1.04-1.66). Conclusiones: Las intervenciones centradas en atacar el problema del abandono durante el proceso de inmunización infantil deberían centrarse en traer más niños a los centros de PAI a tiempo para la primera dosis. La reubicación de centros de PAI ya existentes y la creación de nuevos centros en lugares apropiados podría disminuir el tiempo de viaje a los centros PAI y resultar en menos abandonos. [ABSTRACT FROM AUTHOR]

Background and purpose: Muscarinic stimulation increases myofilament Ca2+ sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca2+ sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC). Experimental approach: Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation level was quantified. Key results: Carbachol (10 µmol·L−1) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 µmol·L−1 isoproterenol (20 ± 1.5% and 56 ± 6.1% above basal respectively). Carbachol-evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M2 receptors antagonized carbachol-mediated inotropic effects with the expected potency. Carbachol-evoked inotropic responses and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho-kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis toxin pretreatment. Conclusion and implications: In failing ventricular muscle, muscarinic receptor activation, most likely via M2 receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca2+ sensitivity. Enhancement of myofilament Ca2+ sensitivity, representing a less energy-demanding mechanism of inotropic support may be particularly advantageous in failing hearts. Mandarin translation of abstract [ABSTRACT FROM AUTHOR]

IgG subclasses are known to be differentially regulated by cytokines (elaborated by activated I cells), which act as growth factors and immunoglobulin switch factors on B cells. In leprosy, we have previously shown that IgG subclass antibodies to a purified recombinant antigen of Mycobacierium leprae (18 000 MW) are restricted to IgG1 and IgG3 across the disease spectrum. The only significant difference observed was that lepromatous patients with low to undetectable T-cell responses showed a strong correlation between IgG1 and IgG3 (P < 0.001) antibodies while tuberculoid patients who showed strong T-cell responses did not show such a correlation. To examine if these differences were related to T-cell-mediated class switching in tuberculoid leprosy patients, we have studied epitope recognition by IgG1 and IgG3 using a panel of synthetic peptides spanning the 18000MW molecule in an enzyme-linked immunosorbent assay (ELISA). In lepromatous patients there was little similarity in peptide recognition by IgG1 and IgG3, with IgG1 recognition being restricted to a single dominant carboxy-terminal peptide while the IgG3 antibodies recognized a diverse set of peptides in the N-terminal half of the 18 000 MW molecule. In tuberculoid patients both IgG1 and IgG3 antibody showed recognition of similar peptides in the N-terminal half of the 18 000 MW molecule. Our results therefore support the hypothesis that immunoglobulin class switching is occurring in tuberculoid but not in lepromatous patients. [ABSTRACT FROM AUTHOR]

IgG subclass responses to Mycobacterium leprae 18000MW recombinant antigen (18K) were determined in sera from untreated leprosy patients using an ELISA-based assay with specific monoclonal antibodies. Antibodies to M. leprae 18K were restricted to IgG1 and IgG3 antibodies with higher seropositivity in lepromatous patients (25.5% for IgG1 and 12.8% for IgG3) compared to patients with tuberculoid disease (11.5% for IgG1 and 5% for IgG3). No significant antibody response was detectable in IgG2 and IgG4 in patients with either lepromatous or tuberculoid leprosy. The selective production of antibodies in IgG1 and IgG3 subclasses could not be related to polyclonal activation in these subclasses as all IgG subclasses showed similar elevated levels at the polyclonal level. The major difference noted between lepromatous and tuberculoid leprosy patients with the IgG subclass antibody response was a strong linear correlation between IgG1 and IgG3 responses to M. leprae 18K in lepromatous patients (r = 0.703, P < 0.001) but not in tuberculoid leprosy patients (r = 0.007, P > 0.10) which may be related to immunoglobulin class switching of IgG3 to IgG1 rather than selective shifts in T-helper subsets. Our results therefore, do not support the hypothesis that activation of Th2 cells occurs in lepromatous leprosy; this issue needs further examination. [ABSTRACT FROM AUTHOR]

To explore the relative species specificities of the IgE and IgG antibody responses to helminth infections in man, we studied four pools of sera from patients infected with Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus or Ascaris lumbricoides and ten individual sera from patients with onchocerciasis. IgE antibodies were detected by radioallergosorbent test (RAST) analysis and IgO antibodies by a Staphylococcus protein A radioimmunoassay (Staph A-RIA). Analysis of the binding curves with four different immunosorbents (prepared from antigens of B. malayi, O. volvulus, Dipesalonema viteae and A. lwnbricoides) in the RAST and the binding curves with these same four antigens in the Staph A-RIA confirmed the relative species specificities for both the IgE and IgO antibody responses. Then determination of these antibody levels after specific absorption of the sera with both homologous and heterologous antigens showed that in all instances there was significantly less cross-reactivity with heterologous parasite antigens (i.e. higher species specificity) in the IgE antibody. [ABSTRACT FROM AUTHOR]

The article presents a study which details the accuracy and precision of sonographic fetal biometry performed by nine paramedics from rural Bangladesh. It notes that 180 women, at 7 to 31 weeks' gestation were the participants of this study. Measurements of each fetus were taken by a highly-trained medical doctor and paramedics. It reveals that both inter-and intraobserver measurement errors were within the range reported in literature of studies conducted by technical staff and medical doctors.

Cohort studies have indicated that the survival of individuals with Down's syndrome has dramatically increased over the past 50 years. Early childhood survival in particular has shown major improvement, due largely to advances in cardiac surgery and in general health management. The present study was based on a continuous cohort of 1332 people with Down's syndrome in Western Australia, registered for intellectual disability services between 1953 and 2000. Their life expectancy was 58.6 years, 25% lived to 62.9 years, and the oldest living person is 73 years of age. Life expectancy for males was greater than females by 3.3 years. The substantial increase in survival across the study period means that the life expectancy of people with Down's syndrome is approaching that of the general population, but accompanied by a range of significant mid-life health problems. The findings are of relevance to all developed countries and have considerable implications in terms of the counselling information provided to families at risk of having a child with Down's syndrome. [ABSTRACT FROM AUTHOR]

ABSTRACT Use of high-strength concrete can lead to more economical design reducing the material requirements, weight of structure and extended service life of structure. The effect of fatigue loading is more prominent on the structures using high-strength concrete. Bond between concrete and reinforcing bars is a major factor affecting the performance and sustainability of reinforced concrete structures. Less research is available on the effect of low cyclic fatigue loading on the bond strength of high-strength concrete. In this research, reinforced concrete beams (1165 × 150 × 225 mm) were tested under low cyclic loading with different stress range levels. It can be concluded that the bond strength of high-strength concrete is more than for normal-strength concrete. Low-cyclic fatigue loading decreased the bond strength under monotonic loading by about 43-45%. Energy dissipation during cycling is found to be good. At higher cycles, energy dissipation decreased because of local damages in front of bar ribs. With the increase in number of cycles, change in slip behaviour was found. [ABSTRACT FROM AUTHOR]

Background and Purpose: β-Adrenoceptor (β-AR)-mediated inotropic effects are attenuated and G(i) proteins are up-regulated in heart failure (HF). Muscarinic receptors constitutively inhibit cAMP formation in normal rat cardiomyocytes. We determined whether constitutive activity of muscarinic receptors to inhibit adenylyl cyclase (AC) increases in HF and if so, whether it modifies the reduced β-AR- or emergent 5-HT₄-mediated cAMP-dependent inotropic effects.Experimental Approach: Contractility and AC activity were measured and related to each other in rat ventricle with post-infarction HF and sham-operated (Sham) controls with or without blockade of muscarinic receptors by atropine and inactivation of G(i) protein by pertussis toxin (PTX).Key Results: Isoprenaline-mediated inotropic effects were attenuated and basal, isoprenaline- and forskolin-stimulated AC activity was reduced in HF compared with Sham. Atropine or PTX pretreatment increased forskolin-stimulated AC activity in HF hearts. β-AR-stimulated AC and maximal inotropic response were unaffected by atropine in Sham and HF. In HF, the potency of serotonin (5-HT) to evoke an inotropic response was increased in the presence of atropine with no change in the maximal inotropic response. Interestingly, PTX pretreatment reduced the potency of 5-HT to evoke inotropic responses while increasing the maximal inotropic response.Conclusions and Implications: Although muscarinic constitutive inhibition of AC is increased in HF, it does not contribute to the reduced β-AR-mediated inotropic effects in rat ventricle in HF. The data support the hypothesis that there are differences in the functional compartmentation of 5-HT₄ and β-AR AC signalling in myocardium during HF. [ABSTRACT FROM AUTHOR]

Objective: In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria-tetanus-pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan.Method: We analyzed a cohort of mother-child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrollment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion.Results: Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrollment in multivariable analysis, DTP3 completion was higher among children who were < or =60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06-1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16-2.65), and who were living < or =10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04-1.66).Conclusions: Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts. [ABSTRACT FROM AUTHOR]