Acute appendicitis in the developing world is a morbid disease

IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system.     

Factors Predisposing to the Development of Atrial Fibrillation

Atrial fibrillation (AF) is in most patients (approximately 70%) associated with organic heart disease including valvular heart disease, coronary artery disease, hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, and congenital heart disease, mostly atrial septal defect in adults. In many chronic conditions, determining whether AF is the result or is unrelated to the underlying heart disease, remains unclear. The list of possible etiologies also include cardiac amyloidosis, hemochromatosis and endomyocardial fibrosis. Other heart diseases, such as mitral valve prolapse (without mitral regurgitation), calcifications of the mitral annulus, atrial myxoma, pheochomocytoma, and idiopathic dilated right atrium may present with AF. Atrial fibrillation may occur in the absence of detectable organic heart disease, the so-called “lone AF”, in about 30% of cases. The term “idiopathic AF” implies the absence of any detectable etiology including hyperthyroidism, chronic obstructive lung disease, overt sinus node dysfunction, and overt or concealed preexcitation (Wolff-Parkinson-White syndrome), only to mention a few of other uncommon causes of AF. The autonomous nervous system may contribute to the occurrence of AF in some patients. AF occurs commonly. In patients with valvular heart disease, AF is common, particularly when the mitral valve is involved. The occurrence of AF is unrelated to the severity of mitral stenosis or mitral regurgitation but is more common in patients with enlarged left atrium and congestive heart failure. In patients with coronary artery disease, AF occurs predominantly in older patients, males, and patients with left ventricular dysfunction. Important predictive factors of AF include hypertension, left ventricular hypertrophy and diabetes. The risk of the development of AF, in an individual patient, is often difficult to assess. Increasing age, presence of valvular heart disease, and congestive heart failure increase the risk of atrial fibrillation.     

Essential health care package for children ‐ the ‘Fit for School’ program in the Philippines

High prevalence of poverty diseases such as diarrhoea, respiratory tract infection, parasitic infections and dental caries among children in the developing world calls for a return to primary health care principles with a focus on prevention. The ‘Fit for School’ program in the Philippines is based on international recommendations and offers a feasible, low‐cost and realistic strategy using the principles of health promotion outlined in the Ottawa Charter. The cornerstone of the programme is the use of school structures for the implementation of preventive health strategies. ‘Fit for School’ consists of simple, evidence‐based interventions like hand washing with soap, tooth brushing with fluoride toothpaste and other high impact interventions such as bi‐annual de‐worming as a routine school activity for all children visiting public elementary schools. The programme has been successfully rolled‐out in the Philippines covering 630,000 children in 22 provinces and it is planned to reach 6 million children in the next three years. The programme is a partnership project between the Philippine Department of Education and the Local Government Units with support for capacity development activities from the German Development Cooperation and GlaxoSmithKline.     

Plasminogen activator inhibitor type‐1 is an independent marker of metabolic disorders in young adults born small for gestational age

Summary. Background: Metabolic syndrome (MS) has been associated with being born small for gestational age (SGA). In epidemiological studies plasminogen activator inhibitor type‐1 (PAI‐1) levels have been associated with MS. Few studies have examined this association in subjects born SGA. Patients and methods: Five hundred and fifty‐seven SGA adults (birth weight < 10th percentile) were compared with 671 subjects with a birth weight between the 25th and 75th percentiles (control group). MS was defined using the World Health Organization (WHO) definition. Active PAI‐1 was measured on citrated plasma with bio‐immunoassay. Results: MS was more prevalent in the SGA group (8.7%) than in the control group (5.5%; P = 0.03). In both groups, PAI‐1 concentrations were significantly correlated with waist circumference, plasma triglycerides, homeostatic model assessment‐insulin resistance (HOMA‐IR) and associated with male sex and MS. PAI‐1 concentrations were significantly increased in the SGA group (12.2 ± 21.2 vs. 10.0 ± 13.5 IU mL^?1, P = 0.03) and this remained after adjustment of metabolic variables (P = 0.009). PAI‐1 concentrations above 4.9 IU mL^?1 (= median of PAI‐1 concentration in the control group) were present in 94% of the subjects with MS. Moreover, the adjusted odds ratio (OR) for having elevated PAI‐1 was 1.48 (1.08; 1.95) in the SGA group in comparison with the control group (P = 0.005). Conclusions: PAI‐1 plasma concentrations were significantly increased in SGA subjects independently of MS. These data suggest that elevation of PAI‐1 concentrations might be an indication of an abnormal secretion at the level of the adipose tissue, endothelial cells or liver and implicated in metabolic disorders reported in SGA subjects.     

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests

Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.     

Soil-transmitted helminth and other intestinal parasitic infections among school children in indigenous people communities in Davao del Norte, Philippines

A significant portion of the population in the Philippines consists of indigenous people (IP) groups, approximately 9% or 8.1 million. Data on the health status of these groups are very limited including the status of soil-transmitted helminth (STH) infections. Provision of such data will be of great importance in the formulation of policy on control and prevention of these diseases in this group. This study was conducted in selected villages/barangays in the municipalities of Carmen, Kapalong, San Isidro and Sto. Tomas in the Province of Davao del Norte in Southern Mindanao, Philippines. Parasitologic assessment was performed using Kato-Katz to qualify and quantify STH infections, while nutritional status assessment was based on hemoglobin determination and on nutritional status indicators, i.e., weight-for-age (WFA), height-for-age (HFA), and body mass index (BMI) for age derived from anthropometric measurements. A total of 572 school children participated in the survey, 264 (46.2%) of whom belonged to a specific IP group. Results showed that 34.1% of the school children had at least one STH infection while 5.9% had heavy intensity infections. Cumulative prevalence in IP school children was significantly higher than in non-IP children with rates at 39.0% and 29.9%, respectively (P = 0.021). Overall prevalence of school children with below normal WFA was 29.9%, while prevalence of those with below normal HFA and BMI for age was 42.8% and 14.9%, respectively. Of those examined, 8.3% had below normal hemoglobin levels. There was no significant difference observed between the nutritional status parameters of IP and non-IP school children. The parasitologic parameters reported in this study signify the need to pay more attention to IP children who are at higher risk of morbidity due to helminth infections. Access of IP communities to quality health services, which include mass drug administration (MDA) and health education on a regular basis, must be ensured. Further studies to determine factors that contribute to the higher prevalence of STH among IP groups are recommended.     

Alternate Ventriculo-Atrial Wenckebach Conduction during Ventricular Tachycardia

Although pacing-induced ventriculo-atrial (VA) Wenckebach conduction has been previously described, the occurrence of this phenomenon during ventricular tachycardia has received little attention. The latter is defined as 2:1 VA block in which the conducted beats show progressive lengthening of VA conduction until the sequence is terminated by two or three blocked ventricular beats. This phenomenon was observed in a 16-year-old boy who underwent electrophysiologic study for ventricular tachycardia as a late complication of surgical correction of tetralogy of Fallot. During pacing-induced ventricular tachycardia with a morphology similar to that of the spontaneous tachycardia, 8:4 alternating VA block was observed. This sequence suggested that the AV node was the site of block, the 2:1 block being located at the upper level, and the VA Wenckebach block at the lower level. Alternate VA Wenckebach conduction appears as a possible cause of variation in atrial depolarization intervals during ventricular tachycardias with short cycle lengths.     

Caffeine potentiates the lethality of tumour necrosis factor in cancer cells.

In this study we have investigated the interaction of caffeine, a prototypic methylxanthine, and TNF on the induction of cell death in mouse and human cell lines during progression from G1 to successive phases of the cell cycle. Exposure of cells to TNF (0.1-100 ng ml-1) as single agent for 48 h caused low or no lethality. The rates of cell death increased significantly when cells cultured with TNF for 24 h were exposed to caffeine (2.5-20 mM). The magnitude of the enhancement by caffeine was TNF and caffeine dose-dependent. The most effective response to this combination was observed in the mouse cell lines, WEHI and L929, followed by the human cell lines, HeLa, A375 and MCF-7, respectively. In L929 cells, TNF treatment did not inhibit DNA synthesis during the first S phase of the cell cycle (20-24 h), but it did block the progress toward a second S phase, indicating the cells were arrested at G2 phase or mitosis. Caffeine had great enhancer effect on L929 cells exposed to TNF for 24 h, but the effect was reduced in cells with either less than 24 h or greater than 28 h of exposure. L929 cells stimulated with TNF died via apoptosis, as judged by both morphological criteria and the occurrence of internucleosomal DNA cleavage. Exposure of TNF-treated cells to caffeine caused a greater increase in the proportion of apoptotic cells as well as the extent of internucleosomal DNA fragmentation.     

Non-mammalian “big” neurophysins — complete amino acid sequence of a two-domain MSEL-neurophysin from goose

Vasotocin-associated neurophysin (MSEL-neurophysin) has been purified from goose neurohypophysis through molecular sieving and high-pressure reverse-phase liquid chromatography (HPLC). The protein has a molecular mass (measured by SDS-polyacrylamide gel electrophoresis) of 17kDa in contrast to 10kDa found for the mammalian MSEL-neurophysins. Complete amino acid sequence (131 residues) has been determined mainly through tryptic or staphylococcal proteinase peptides derived from carboxyamido-methylated neurophysin, isolated by HPLC and microsequenced. N- and C-terminal sequences have been established by Edman degradation or action of carboxypeptidase Y, respectively, applied on the native protein. Goose MSEL-neurophysin is homologous to the two-domain “big” MSEL-neurophysin previously identified in the frog. It appears that in non-mammalian tetrapods, namely birds and amphibians, the proteolytic processing of the pro-vasotocin involves only one cleavage, releasing the hormone moiety and a “big” neurophysin with two domains homologous to mammalian MSEL-neurophysin and copeptin, respectively. Comparison of the avian protein with its mammalian and amphibian counterparts reveals that the first half of the polypeptide chain is evolutionarily much less variable than the second and that the goose protein resembles the frog protein much more than the mammalian one.     

Retrograde (Ventriculoatrial) Conduction

Ľinterêt dans la conduction VA rétrograde a été renouvelé depuis la découverte de tachycardies induites par les stimulateurs cardiaques de type physiologique qui incorporent le recueil des potentiels auriculaires. Seule ľétude de la conduction VA rétrograde associée à une parfaite connaissance de son comportement électrophysiologique dans dif-ferents cos, permettra de dépister les malades susceptibles de faire une tachycardie induite par le stimulateur.
Interest in retrograde VA conduction has been renewed with the advent of tachycardias induced by physiologic pacemakers with atrial sensing capabilities. Accurate representation of ventriculoatrial conduction requires detailed electrophysiologic analysis during sinus rhythm, during tachycardias whether or not associated with accessory pathways, and during ventricular pacing studies. Retrograde conduction should be assessed in patieifts considered for implantation of atrial sensing and tracking pacemakers (VAT, VDD, DDD), until technologic advances overcome the problems of endless loop tachycardias.