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Ethical challenges to Medical Professionalism: Zimbabwe 2006
In recent years organisations of doctors in many countries have become concerned with the concept and practice of professionalism. In this article I apply these concerns to local circumstances in Zimbabwe, aiming to identify the most important area
A Dimeric Calcium-modulated GC-linked Receptor Kinase, PSKR1
AbstractThe phytosulfokine receptor 1, PSKR1 is a membrane-localised leucine-rich repeat receptor-like kinase that also possesses intrinsic guanylate cyclase (GC) activity. The GC activity is conferred, in part, by the presence of a GC catalytic centre that is embedded within its kinase domain. This unusual domain architecture represents a novel class of GC-linked receptor kinases. This novel class of kinases was unearthed using sequence homology-guided bioinformatic data mining tools. Only four members of this new class of kinases have been shown to possess both kinase and GC activity. Currently, there is a paucity of information as to how this dual catalytic activity is regulated in these molecules; therefore we set out to explore the regulatory factors that modulate the dual catalysis in this unusual family of receptor kinases. Our functional studies on PSKR1 demonstrate that calcium acts as a molecular switch regulating this dual catalysis. Functional analysis of PSKR1 at different calcium concentrations showed that calcium inhibits the kinase activity of PSKR1 in a concentration dependant manner whilst on the other hand, enhancing the GC activity of PSKR1. Our previous studies have also demonstrated that, cyclicGMP (a product of GC activity) inhibits the kinase activity of PSKR1. Taken together, our observations indicate that calcium and cyclicGMP act as molecular switches of PSKR1-mediated signalling. Furthermore, our structural analysis of the cytoplasmic domain of PSKR1 suggests that it exists as a reversible dimer in solution. This observation may represent a physiological conformation of PSKR1. In a separate experiment, using tandem mass spectrometry, we have mapped out the phosphorylation pattern of the cytoplasmic domain of PSKR1. Our findings show that the cytoplasmic domain of PSKR1 has 14 phosphorylation sites in its cytoplasmic domain including 3 phospho-tyrosines. This current study presents a mechanistic model of how calcium and phosphorylation act as bimodal switches regulating the dual catalysis in PSKR1
The relationship between social support among HIV positive mothers and exclusive breastfeeding feeding practice during the first 6 months of life at Rusape district hospital.
One in three children under the age of 6 months are exclusively breastfed, this translates to 33% (ZDHS, 2011), which is very low that is against WHO (2010) recommendations. Study was conducted at Rusape District Hospital, respondents were HIV positive mothers who breastfed for the first 6 months (mean = 22, median = 23, mode = 25, SD = 3.616). Study sought to find out relationship between social support and exclusive breastfeeding (EBF) practice among HIV positive mothers and a quantitative descriptive correlational study design was utilized. Health Promotion Model (Pender, 1982) guided the study. Non-probability convenience sampling method and 85 respondents were selected. A structured interview schedule was used to collect data from demographics, social support and EBF practices. Data was analyzed using descriptive statistics and inferential statistics. Study findings were that 75% respondents initiated breastfeeding within an hour, while 100% respondents did not offer pre-lacteal feeds, 87.1% perceived that had adequate breast milk for baby up to 6 months, 96.5% agreed it was practical to EBF their babies while on ART. Only 69.4% EBF their babies, 83.5% respondents received informational support, and 95.3% respondents received material support. Eighty nine percent cited midwife as influential to their decision to EBF. Pearson Correlation revealed significant positive moderate relationship (r = .382, p = .01). Regression Analysis revealed linear relationship (Adjusted R2 = .136) social support was responsible for 13.6% changes in EBF practices. F statistics (F = 14.2, p = .00) showed significant R2, Beta (b = .382, p = .01) was .382 that is for every unit change in social support, EBF practices would improve by 38.2%. Midwives should capitalize being valued referent to shape EBF behaviors through health education
A pilot study to assess the immunologic and virologic efficacy of generic nevirapine, zidovudine and lamivudine in the treatment of HIV-1 infected women with pre-exposure to single dose nevirapine or short course zidovudine and their spouses in Chitungwiza, Zimbabwe
Objective: A pilot study to assess effectiveness of generic Nevirapine (NVP)+Zidovudine(AZT)+Lamivudine (3TC) as potent antiretroviral therapy (ART) in women exposed to either SD NVP or short course (SC) AZT through participation in prevention of mother-to-child transmission of HIV-1 (pMTCT) interventions, and their spouses.
Design: A pilot study of antiretroviral treatment of adults with AIDS.
Setting: Primary health care clinics; Seke North and St Mary’s in Chitungwiza, Zimbabwe.
Subjects: Women with pre-exposure to SD NVP or SC AZT and their spouses with CD4 count <200 cells/ pL.
Interventions: Generic AZT/3TC twice daily plus NVP daily for the first 14 days and then twice a day thereafter, administered to the cohort.
Main Outcome Measures: The baseline median CD4 count for women and men was 128.5 and 119.0 cells/ pL respectively. The geomean virus load was similar for the women and men. At weeks 16,24 and 48,82.8%, 85.1% and 73.8% had 98%
Factors associated with Human Immunodeficiency Virus (HIV) testing and counseling among couples, Bulawayo city, 2015
Background: Majority of people in stable relationships are not aware of their HIV status.
Bulawayo City HTC data showed a decline in the proportion of urban couples who were
tested for HIV from 11% in 2010 to 6.7% in 2014.The study was conducted to determine
factors associated with HTC among couples in Bulawayo City.
Methods: A one to one unmatched case control study was conducted. A total of 254 women, 127 cases and 127 controls, were recruited. A case was a woman aged 16-35 years who did not receive HTC with her partner. A control was a woman aged 16-35 who had received HTC with her partner. A pretested interviewer administered questionnaire was used to collect data from conveniently selected participants. Bivariate and logistic regression analyses were conducted to identify effect modification and control for confounding.
Results: Staying within a distance of less than 5 km from the health the health facility
(AOR=0. 38, 95% CI: 0.21-0.71) and prior discussion of HTC as a couple (AOR=0. 43, 95% CI: 0.21-0.87) were independently associated with more likelihood of receiving HTC as a couple. Conflicting work schedules (AOR=2.99, 95% CI: 1.17-5.11) and perceived low risk (AOR=1.78, 95% CI: 1.02-3.10) were found to be independent risk factors for not receiving HTC as a couple.
Conclusion: Testing as a couple was as a result of factors relating to distance of less than 5 km from the health facility, prior discussion of HTC as a couple, low risk perception and conflicting work schedules. Encouraging communication among couples and health education may improve HTC among couples
INVESTIGATION OF THE TOXICOLOGICAL AND PHARMACOLOGICAL ACTIVITY OF A HYDROETHANOLIC EXTRACT OF BOOPHONE DISTICHA BULB
Boophone disticha is a highly poisonous bulb. It has been used systemically in traditional medical practice in Zimbabwe and neighbouring countries for the management of various central nervous system conditions including hysteria. Abuse of the plant by teenagers in Zimbabwe for its claimed hallucinogenic effects has also been reported, with the advent of serious toxicity in some cases.
The aim of the present work was to describe the symptomatology, neurotoxicological effects and lethality of acute and subacute ingestion and of a hydro-ethanolic plant extract of the bulb of Boophone disticha in rats. Initially, we set out to estimate the LD50 of this extract using a modified Up-and-down procedure for acute toxicity determination. We then used a Functional Observational Battery (FOB) to identify the neurotoxicological effects of the extract after both acute and repeated oral intake. Additionally we studied the genotoxic potential of the Boophone extract using the Ames test. Finally we sought to investigate the putative neuropharmacological effects i.e. anxiolytic-like and antidepressant-like activity in a murine model.
Findings in the acute toxicity and neurotoxicological assessment, showedan estimated oral LD50 of between 120 and 240 mg/kg. For doses of 240 mg/kg and less, signs of toxicity began approximately 10 minutes after gavage, and the most prominent initial signs were head tremors (at 50 mg/kg) and body tremors, severe body tremors(>360 mg/kg) followed by convulsions. Generally, symptoms of toxicity lasted approximately 2 hours for doses of 240 mg/kg and less; and 3 hours for doses over 240 mg/kg for animals that survived. These results point to a rapid gastrointestinal absorption of the active principles in the plant extract. The most prominent neurotoxicological effects were increased flaccid limb paralysis and spastic hind-limb paralysis. Tachypnoea was noted at low doses and higher doses produced laboured breathing. The retropulsion observed with higher doses could indicate the reported hallucinogenic effects of the plant extract.
Subacute assessment showed the similar profile symptoms as with acute toxicity.The main subacute toxic effects of Boophone disticha like the acute effects seem to be mediated via interference with the neuronal pathways especially the central dopaminergic and motor neurons. Target organs, as observed by changes in organ weight appear to be liver, small and large intestines, stomach, central nervous system and peripheral nervous system. Boophone disticha extract was genotoxic from concentrations 1000μg/plate and above with both TA98 and TA100 Salmonella typhimurium species irrespective of the metabolic status of the system. The 500μg/plate concentrations of the Boophone extract were not associated with any genotoxicity and 2500μg/plate concentration is potential cytotoxic which could have masked the genotoxic effects at this concentration.
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Boophone disticha extract showed Anxiolytic-like activity in the elevated plus maze test by significantly changing the percentage time spent in open arms, number of open arm entries, rearing, unprotected head dips and stretch attend postures. The 10m/kg dose had the most prominent effects compared to the higher dose which were comparable to the positive control. Repeated dosing enhanced the antidepressant-like activity of the Boophone extract.
Therefore from the pharmacological findings of our studies, despite being very toxic Boophone disticha proved to be an important source of lead compounds for future drug development. Therefore further investigations are necessary to determine the target site and efficacy of Boophone alkaloids with in vivo models.This work was supported by IFS grant number F/4187-
Dilatation of the oesophagus associated with oesophageal varices in portal hypertension
In this short publication I merely wish to draw attention to the not altogether rare finding of dilatation of the oesophagus in Africans suffering from cirrhosis of the liver and portal hypertension. It is quite possible that this finding is already recorded in the literature, blit the purpose of this short communication is to draw attention to it in Rhodesi
Randomised control trial comparing two regimens of prophylactic antibiotics for women undergoing caesarean section
Introduction
Infection is one of the major complications of surgery. Caesarean section is the single most important risk factor for postnatal infections [2]. Prophylactic antibiotics have become a standard of management for people undergoing surgery. According to the EDLIZ 2006, women undergoing caesarean section should be given a single dose of Benzyl penicillin 5MU iv and Chloramphenicol 1gram iv. However at Parirenyatwa and Harare hospitals, patients get antibiotics for an average of 7days. The prolonged course which is in practice increases the work load on the hospital staff which is already overwhelmed due to understaffing. It also increases costs to the patients, demands patient compliance and increases risks of antibiotics resistance. We did a study to see if the current practice can be justified. We compared current practice of prophylactic antibiotics to a proposed single dose regime of prophylactic antibiotics for women undergoing caesarean section. The current practice was standardized for the purpose of this study.
OBJECTIVES:
Main Objective
To compare the effectiveness of “single dose ceftriaxone and metronidazole” with the current practice of week-long course of prophylactic antibiotics for caesarean section.
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METHODOLOGY
A prospective Randomized Control Trial was done at Parirenyatwa and Harare hospitals from 2 February 2012 to 30 May 2012. Women undergoing caesarean sections were recruited following an inclusion and exclusion criteria. These were randomized into Arm 1 and Arm 2. Those in Arm 1 were given a single dose of Ceftriaxone and Metronidazole preoperatively and no more antibiotics postoperatively, except for treatment. Those in arm 2 were given a standardized week-long course of antibiotics representing the current practice. The patients were followed up for 6weeks.
The sample size of 260 patients was calculated, which meant 130 patients were needed for each arm. 280 patients were initially recruited but at the end, 232 were analysed after losing some patients during follow-up (see flow diagram).
RESULTS
Two hundred and thirty two patients were analyzed. 112 were in Arm 1 while 120 were in arm 2. These were compared for the incidence of hyperpyrexia, admission with puerperal sepsis, wound sepsis, prolonged hospital stay, laparotomy for pelvic abscess and mortality. Infective morbidity was defined by the presence of at least one of the above parameters. Infective morbidity occurred in 28 out of 232 (12%). 15 of these patients were in ARM 1 (Single dose group) while 13 were in ARM 2 (Week – long group). The difference was not statistically significant..
CONCLUSIONS
In this setting, the administration of single dose preoperative ceftriaxone 1g in combination with metronidazole 500mg, is clinically equivalent to the current practice of week-long course of antibiotics for the prevention of puerperal infections. We therefore recommend the single dose regimen due to lower costs and lesser burden to hospital staff who will administer reduced number of doses of antibiotic