Apoptosis as a form of cell death in intracerebral hemorrhage

OBJECTIVE: The goals of this study were to identify and quantify the presence of programmed cell death (apoptosis) in intracerebral hemorrhage (ICH) among human subjects. Recent evidence from laboratory models suggests that cell death in the perihematoma region may involve apoptosis. METHODS: Retrospective clinical and histological analyses were performed for patients with spontaneous ICH who underwent surgical evacuation. Quantification of apoptotic cells was performed in sections obtained from the perihematoma region from 12 patients with ICH and stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling method. Necrosis was identified on the basis of morphological criteria, using hematoxylin and eosin staining. RESULTS: Evidence of apoptosis was present in surgical specimens obtained from 10 of the 12 patients. The mean number of apoptotic cells in the perihematoma region in each patient specimen was 38% (range, 0-90%). For five patients, more than one-half of the total cells observed were apoptotic. Apoptosis was observed in specimens obtained within 1 day, 2 days, and 5 days after the onset of symptoms. No terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling-positive cells were observed in specimens from the two patients with cerebellar hematomas. The mean proportion of necrotic cells in the perihematoma region in each patient specimen was 25% (range, 0-100%). There was a prominent excess of apoptotic cells, in comparison with necrotic cells, for 6 of the 12 patients who underwent hematoma evacuation. For five other patients, similar proportions of apoptotic and necrotic cells were observed. Necrosis was the predominant finding for only one patient, who underwent late surgical evacuation on Day 5. CONCLUSION: These observations suggest that apoptosis represents a prominent form of cell death associated with ICH in the perihematoma region. Further studies are required to define the mediators of apoptosis in ICH.     

Prevalence of early childhood disability in a rural district of Sind,Pakistan

Aim

Children born in low‐ and mid‐income countries are at a high risk of developing disabilities, yet estimates of population‐based prevalence are sparse. Our aim was to determine the prevalence of early childhood (0–5 year) disability in Sind, a rural area of Pakistan.

Method

We conducted a cross‐sectional household survey in a population of 25 196 households. The Ten Questions screen and the Signs of Disability in Newborn and Infants screen were used.

Results

The disability prevalence in a population of 176 364 individuals was 5.5 out of 1000 in children under 2 years and 5.4 out of 1000 in children aged 2–5 years. Fifty‐six per cent were males, and 56% had the disability recognized from birth or soon after. The mortality rate of children aged 0–5 years in the area was estimated as 30 out of 1000 live births. Cerebral palsy was the most common disability identified. The Ten Questions screen had better interrater agreement than the Signs of Disability in Newborn and Infants screen.

Interpretation

This is the largest reported household screening survey for early childhood disability at a population level from rural Pakistan. The comparatively low prevalence may be due to the younger age studied and high early childhood mortality. Our data highlight the importance of prospective surveillance at a population level and the need for preventive and support services.     

Is the modified Mallampati test performed in supine position a reliable predictor of difficult tracheal intubation?

Management of the airway is central to the practice of anesthesia. Several bedside airway assessment methods have been proposed for preoperative identification of patients who are difficult to intubate. The modified Mallampati test (MMT) remains a time-tested technique to date for recognizing an anticipated difficult tracheal intubation as assessed by Cormack–Lehane grade. Both Mallampati and its further modification by Samsoon and Young evaluate patients in the seated position. Recently a study mentioned a change in MMT score from sitting to supine position toward the higher side. However, there is a lack of data regarding the relationship of positional change in MMT with Cormack–Lehane grade. The aim of this prospective study was to assess if MMT score observed in sitting or supine position is a better predictor of difficult tracheal intubation. One hundred and twenty-three patients of ASA physical status I and II, aged 18–60 years, who were scheduled to undergo various neurosurgical procedures were enrolled for the study. We found that the MMT in supine position has a higher positive predictive value and is associated with more true positives as compared to MMT in the sitting position.     

Effect of vancomycin on the cytoplasmic membrane fatty acid profile of vancomycin-resistant and -susceptible isolates of Staphylococcus aureus

This study was designed to analyze the effect of vancomycin on the cytoplasmic membrane fatty acid (FA) composition of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-susceptible S. aureus. One low-level vancomycin-resistant isolate (LLR-VRSA) termed CP2, along with two vancomycin intermediate-resistant S. aureus isolates (VISA-CP1) and Mu50 (ATCC #700699), were studied. The LLR-VRSA isolate CP2, recovered from the blood sample of a postoperative cardiac patient, exhibited vanA type vancomycin resistance [minimum inhibitory concentration (MIC) 16 μg/ml], and the vanA cassette was located on a plasmid. CP1, isolated from the pus sample of the same patient, exhibited vancomycin intermediate resistance (MIC 8 μg/ml) in the absence of the vanA, vanB, or vanC gene. As susceptible controls, we used PSA (vancomycin MIC 2 μg/ml), which was isolated from the pus sample of a neonate, and S. aureus (ATCC# 29213). Membrane FA analysis was carried out using gas chromatography coupled with mass spectrometry. For this purpose, CP1, CP2, Mu50, and the susceptible control isolates were grown in the presence and absence of vancomycin. Comparative analysis showed an increase in the relative proportion of unsaturated FAs during growth under vancomycin stress. The isolate CP2 (LLR-VRSA) exhibited a higher MIC to vancomycin than the other isolates used in present study (16 μg/ml) and under vancomycin stress conditions, quantitatively, it showed a high rate of conversion of saturated to unsaturated membrane FAs than CP1, Mu50 (VISA isolate) and the susceptible control PSA. The rate of saturated-to-unsaturated FA conversion increased as the concentration of vancomycin in the growth media was increased. Therefore, it is concluded that S. aureus tend to modify their membrane lipid chemistry from saturated to unsaturated in order to survive in a vancomycin stress environment.     

How many child deaths can we prevent this year?

This is the second of five papers in the child survival series. The first focused on continuing high rates of child mortality (over 10 million each year) from preventable causes: diarrhoea, pneumonia, measles, malaria, HIV/AIDS, the underlying cause of undernutrition, and a small group of causes leading to neonatal deaths. We review child survival interventions feasible for delivery at high coverage in low-income settings, and classify these as level 1 (sufficient evidence of effect), level 2 (limited evidence), or level 3 (inadequate evidence). Our results show that at least one level-1 intervention is available for preventing or treating each main cause of death among children younger than 5 years, apart from birth asphyxia, for which a level-2 intervention is available. There is also limited evidence for several other interventions. However, global coverage for most interventions is below 50%. If level 1 or 2 interventions were universally available, 63% of child deaths could be prevented. These findings show that the interventions needed to achieve the millennium development goal of reducing child mortality by two-thirds by 2015 are available, but that they are not being delivered to the mothers and children who need them.     

Ethics in international health research: a perspective from the developing world

Health research plays a pivotal role in addressing inequities in health and human development, but to achieve these objectives the research must be based on sound scientific and ethical principles. Although it is accepted that ethics play a central role in health research in developing countries, much of the recent debate has focused on controversies surrounding internationally sponsored research and has taken place largely without adequate participation of the developing countries. The relationship between ethical guidelines and regulations, and indigenously sponsored and public health research has not been adequately explored. For example, while the fundamental principles of ethical health research, such as community participation, informed consent, and shared benefits and burdens, remain sacrosanct other issues, such as standards of care and prior agreements, merit greater public debate within developing countries. In particular, the relationship of existing ethical guidelines to epidemiological and public health research merits further exploration. In order to support health research in developing countries that is both relevant and meaningful, the focus must be on developing health research that promotes equity and on developing local capacity in bioethics. Only through such proactive measures can we address the emerging ethical dilemmas and challenges that globalization and the genomics revolution will bring in their wake.     

Impact of age and drug resistance on mortality in typhoid fever

The risk factors for mortality were analysed in a consecutive group of 1158 children presenting to the Aga Khan University Medical Center, Karachi, with multidrug resistant typhoid fever that had been proved on culture. There were 19 deaths, representing an overall case fatality rate of 1.6%. Multidrug resistant typhoid was associated with a more severe clinical illness and higher rates of toxicity, hepatomegaly, hypotensive shock, and death. Irrespective of drug resistance status, typhoid fever was found to be a more severe illness in young infants with significantly higher rates of diarrhoea, hypotensive shock, and mortality. Univariate analysis of admission characteristics associated with increased risk for mortality revealed significant association with younger age (p < 0.05), hypotensive shock or hypothermia (p < 0.001), obtundation (p < 0.001), seizures (p < 0.05), anaemia at admission (p < 0.005), and leucocytosis (p < 0.001). Logistic regression analysis of risk factors for mortality showed persistent association of hypothermia, toxicity, and anaemia with mortality. The data provides evidence that multidrug resistant typhoid in childhood is associated with increased risk of mortality, especially in infancy and closer attention to several risk factors for increased morbidity and case fatality rates may lead to improved outcome of treatment.