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Biomedical subjects

P Manga

Publications and source records attributed to P Manga.

At least 19 recordsLinked to original sources
PubMed2002

Children with intellectual disability in rural South Africa: prevalence and associated disability.

The objective of the present study was to determine the prevalence of intellectual disability (ID) and its associated disabilities in rural South African children aged 2-9 years. It was undertaken in eight villages in the district of Bushbuckridge, Northern Province, South Africa. A two-phase design was utilized. The first phase involved screening children on a house-to-house basis by interviewing mothers or caregivers using an internationally validated questionnaire for detecting childhood disability in developing countries. The second phase consisted of a paediatric/neurodevelopmental assessment of the children who screened positive. A total of 6692 children were screened; 722 (10.8%) had a paediatric evaluation and 238 children were diagnosed with ID, giving a minimum observed prevalence of 35.6 per 1000 children in this population. The prevalence of severe and mild ID was 0.64 per 1000 and 29.1 per 1000 children, respectively. The male:female ratio of children with ID was 3:2. In the affected children, a congenital aetiology for the ID was determined in 49 subjects (20.6%), an acquired aetiology in 15 (6.3%) and the aetiology was undetermined in 174 children (73.1%). Epilepsy (15.5%) and cerebral palsy (8.4%) were the commonest associated disabilities. The present study represents the first data on the prevalence of ID and associated disabilities in rural South African children. The prevalence of ID was comparable with results from a study performed in one other African country (Zambia) as well as those from other developing countries. The data provide an initial factual insight into ID and its associated disabilities for healthcare, social service and educational policy planners. This study provides a basis for the initiation and development of appropriate and integrated services for the best possible care of individuals affected with these disabilities, and for their possible prevention.

Child↗
PubMed2001

In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified.

In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; theta=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype.

Albinism, Oculocutaneous↗
PubMed2001

Mislocalization of melanosomal proteins in melanocytes from mice with oculocutaneous albinism type 2.

More than 10% of admissions worldwide to institutions for the visually impaired are due to some form of albinism. The most common form, oculocutaneous albinism type 2, results from mutations at the p locus. The function of the p gene is yet to be determined. It has been shown that melanocytes from p -null mice exhibit an abnormal melanosomal ultrastructure in addition to alterations in activity and localization of tyrosinase, a critical melanogenic enzyme. In light of these observations, we examined tyrosinase trafficking in p -null vs wildtype mouse melanocytes in order to explore p function. Electron microscopy of wildtype melan-a and p -null melan-p1 cells demonstrated accumulation of tyrosinase in 50 nm vesicles throughout the cell in the absence of p, an observation corroborated by an increase in tyrosinase activity in vesicle-enriched fractions from melan-p1 compared to melan-a cells. Misrouting in the absence of p was not limited to tyrosinase; a second melanosomal protein, tyrosinase-related protein 1, also trafficked incorrectly. In melan-p1, mislocalization led to secretion of tyrosinase into the medium. Adding tyrosine to the medium was found to partially correct tyrosinase trafficking and to reduce secretion; the cysteine protease inhibitor E64 also reduced secretion. We propose that p is required by melanocytes for transport of melanosomal proteins. In its absence, tyrosinase accumulates in vesicles and, in cultured melanocytes, is proteolysed and secreted.

Albinism, Oculocutaneous↗
PubMed2001

Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1.

The pink-eyed dilution protein (p) plays a pivotal role in the synthesis of eumelanin. In its absence, critical melanosomal proteins fail to traffic to the melanosome. Pink-eyed dilution gene (P) mutations are the most common cause of tyrosinase-positive oculocutaneous albinism worldwide. Thus, reports that bafilomycin A1 was able to induce synthesis of melanin in tyrosinase-positive melanomas led us to test the drug on p-null murine melanocytes. We found that in melanocytes lacking p, bafilomycin A1 was able to induce melanin synthesis. These cells, once transfected with an expression vector encoding an epitope-tagged p transcript, failed to respond to the drug. The increase in melanin synthesis is accompanied by a reduction in tyrosinase protein cleavage and secretion with subsequent accumulation within the melanocyte. Bafilomycin A1 has also been reported to induce pigmentation of normal Caucasian melanocytes. Based on these data we hypothesize that p may serve as a key control point at which ethnic skin color variation is determined.

Animals↗
PubMed2001

Euthanasia and medically assisted suicide--the case for legalizing physician assisted suicide.

Ethical and legal debates over ending life are inescapably emotive, controversial and complex. It is, however, increasingly urgent to resolve the debate over the legalization or continued prohibition of physician assisted suicide for a number of reasons, not least of which is the changing public and professional opinion and the growing concern over what may be actually but quietly and surreptitiously occurring in medical practice. The paper assesses the arguments for and against the legalization of this special case of euthanasia and concludes that with appropriate and well-defined criteria, guidelines, review and reporting requirements, the legalization of physician assisted suicide is not only ethical defensible but practical.

Empathy↗
PubMed2000

Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa.

Oculocutaneous albinism (OCA) is an inherited disorder resulting in hypopigmentation of the skin, hair, and eyes. OCA type 2 (tyrosinase-positive) is the most common recessively inherited disorder among southern African Blacks. OCA2 is also seen in southern African Caucasoids, but is less frequent. The gene responsible for this type of albinism, P, is the human homolog of the mouse pink-eyed dilution gene. Mutations at this locus are also responsible for the milder hypopigmentation phenotype seen in individuals with brown oculocutaneous albinism (BOCA). A common African P mutation was identified in Black OCA2 individuals, and has since been shown to occur in Black individuals with brown OCA as well. This mutation is a 2.7 kb interstitial deletion. In this study, we undertook to screen the coding region of the P gene for mutations in the non-2.7 kb deletion alleles of OCA2 patients who did not carry the deletion allele in either one or both of their P genes. We identified four mutations (A334V, 614delA, 683insG [corrected], 727insG) in a group of 39 unrelated Black OCA2 patients with a total of 52 non-2.7 kb deletion OCA2 genes. When taking all OCA2 cases into consideration, including those homozygous for the 2.7 kb deletion mutation, these account for a further 1.7% of OCA2 mutations in southern African Blacks, increasing the overall mutation detection rate to 78.7%. Three mutations (E678K, L688F, I370T) were identified in a group of 15 Black patients with an initially unclassified type of OCA and another three mutations (IVS 14-2 (a-->g), V350M, P743L) were identified in nine Caucasoid OCA patients. Relatively few mutations, all with low frequency, were identified in the non-2.7 kb deletion OCA genes. We propose that other mutations may lie either within intronic sequence or within the promoter region of the gene.

Africa South of the Sahara↗
PubMed2000

Economic case for the integration of chiropractic services into the health care system.

The role and position of chiropractic care in the health care system must be transformed from being alternative and separate to alternative and mainstream. This transformation requires that chiropractic services become integrated in the many health care delivery organizations that collectively constitute the health care system. There is solid and impressive economic and related justification for the desired integration. Chiropractic care is a cost-effective alternative to the management of neuromusculoskeletal conditions by other professions. It is also safer and increasingly accepted by the public, as reflected in the growing use and high patient retention rates. There is much and repeated evidence that patients prefer chiropractic care over other forms of care for the more common musculoskeletal conditions. The public interest will be well served by this transformation. Musculoskeletal disorders and injuries are the second and third most costly categories of health problems in economic burden-of-illness studies. They rank first as a cause in the prevalence of chronic health problems and long-term disability and rank at the top for activity limitations and short-term disability. They rank first as a reason for consultation with a health professional and second as a reason for the use of prescription and nonprescription drugs. These conditions are more prevalent among the poor, lower-middle income groups, and the elderly, yet those are precisely the groups that make the least use of chiropractic care for reasons of inadequate insurance coverage. The integration of chiropractic care into the health care system should serve to reduce health care costs, improve accessibility to needed care, and improve health outcomes.

Chiropractic↗
PubMed2000

Mutational analysis of the modulation of tyrosinase by tyrosinase-related proteins 1 and 2 in vitro.

The albino (tyrosinase, Tyrc), brown (tyrosinase-related protein 1, Tyrp1b) and slaty (tyrosinase-related protein 2, tyrp2slt) loci are all involved in the regulation of melanogenesis. Phenotypes of inbred mice mutant at two or more of these loci are not always explicable by simple summation of the established or suspected catalytic functions of the gene products. These phenotypes suggest that relationships among the proteins extend beyond the obvious fact that they catalyze different steps in the same melanogenic pathway, and that they may also interact intimately in such a way that a mutation in one impacts the function of the other(s). Previous studies have attributed catalytic activities to each member of this trio; however, it has been difficult to study the proteins individually, either in vivo or in tissues or cells. Therefore, we undertook to transfect the genes, in revealing combinations, into COS-7 cells (which have no melanogenic apparatus of their own) to clarify the interacting functions of their encoded proteins. Specifically, we attempted to evaluate the effects of Tyrp1 and Tyrp2 proteins on tyrosinase protein. We report evidence that Tyrp1 stabilizes tyrosinase, confirming previous observations, and, in addition, demonstrate that Tyrp1 decreases tyrosinase activity. By contrast, Tyrp2 increases tyrosinase activity by stabilizing the protein. We conclude that both Tyrp1 and Tyrp2, in addition to other catalytic functions they may possess, act together to modulate tyrosinase activity.

Animals↗
PubMed2000

Epilepsy in rural South African children--prevalence, associated disability and management.

OBJECTIVE: To determine the prevalence of epilepsy and its associated disabilities in rural South African children aged 2-9 years. SETTING: Eight villages in the district of Bushbuckridge, Northern Province, South Africa. DESIGN: A two-phase design was used. The first phase involved screening children on a house-to-house basis by interviewing mothers or caregivers using an internationally validated questionnaire for detecting childhood disability in developing countries. The second phase consisted of a paediatric/neurodevelopmental assessment of the children who screened positive. RESULTS: A total of 6,692 children were screened; 722 (10.8%) had a paediatric evaluation and 49 (0.73%) had epilepsy. The lifetime and active prevalences of epilepsy in these children were 7.3/1,000 and 6.7/1,000 respectively. Associated developmental disability was recorded in 35 affected children (71.4%), including 8 (16.3%) in whom this was moderate to severe. More than a half of the children with epilepsy (57.1%) did not receive anticonvulsant medication. CONCLUSION: The prevalence of epilepsy in the rural childhood population investigated is higher than that recorded in most similar studies from sub-Saharan Africa, and the poor utilisation of appropriate anticonvulsant treatment is cause for concern. This study highlights the paucity of relevant information on the epidemiology of epilepsy in South Africa and that the system available for its management, especially in rural areas, appears to have functional deficiencies. Appropriate research is needed to identify the problems in service delivery and to enable the planning and implementation of an appropriate primary health care-based system for the diagnosis and management of epilepsy in children.

Child↗
PubMed2000

The Quattro valve and active infective endocarditis of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Even today, infective endocarditis remains a therapeutic challenge. Active endocarditis at the time of valve implantation is an important risk factor for the development of prosthetic valve infection. This study reports results following implantation of the Quattro valve, a stentless chordally supported quadrileaflet mitral valve made from bovine pericardium. METHODS: The Quattro valve was implanted in seven patients (four females, three males; mean age 34 years) requiring isolated mitral valve replacement for active bacterial endocarditis. All had congestive heart failure; two were in cardiogenic shock. The diagnosis of active endocarditis was based on clinical and echocardiographic findings, together with macroscopic evidence of acute infection at surgery, blood culture or histopathological evidence of valve infection. Postoperatively, all patients received at least four weeks of parenteral antibiotic therapy. RESULTS: Congestive heart failure (and large pedunculated vegetations and mobile septic left atrial thrombi in two patients) prompted early surgical intervention. Patients underwent surgery at a mean of 7 days (range: 1-16 days) after admission. Endocarditis was caused by Gram-positive cocci in all patients except one. At a mean follow up of 15 months (range: 6-24 months) all patients were alive and symptomatically improved. To date, all remain free of prosthetic valve endocarditis, reoperation and thromboembolism. CONCLUSION: The Quattro valve can be implanted safely in patients with acute bacterial endocarditis. The results also reflect the benefit of early surgical intervention in patients with infective endocarditis complicated by congestive heart failure, with or without large vegetations.

Adult↗
PubMed1999

The stentless quadrileaflet bovine pericardial mitral valve: early clinical results.

BACKGROUND AND AIMS OF THE STUDY: Although bioprosthetic valves currently in use have low thrombogenicity, durability remains very unsatisfactory. Valve failure occurs early from calcification, and later from tissue wear. Stentless design lessens the latter, and anticalcification treatments the former. Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium, treated to minimize calcification, has become available for clinical study. The aim of this study was to report the early results relating to valve performance, and patient outcome. METHODS: Since December 1996, the QMV has been implanted in 23 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not suited for repair. All patients were symptomatic (three in NYHA functional class II, 16 in class III, four in class IV). Preoperatively, all underwent full clinical and echocardiographic assessment, and intraoperative transesophageal evaluation immediately after valve implantation. Blood tests for hemolysis were performed preoperatively and at 3 months after surgery. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), 22 patients were alive and symptomatically improved (NYHA class I or II). One patient died of sternal sepsis soon after surgery. There have been no reoperations, nor cases of infective endocarditis or thromboembolism. Subclinical hemolysis was shown pre- and postoperatively in 35% and 32% of cases, respectively. Intraoperative transesophageal echocardiography post valve implantation demonstrated mitral regurgitation which was trivial in 15 patients (78%) and mild in five (22%). CONCLUSIONS: The QMV can be implanted safely, and the early clinical results relating to patient outcome and valve performance are encouraging.

Adult↗
PubMed1999

The stentless quadrileaflet bovine pericardial mitral valve: echocardiographic assessment.

BACKGROUND AND AIMS OF THE STUDY: Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium treated to minimize calcification, has become available for clinical trial. The aim of this study was to report both the echocardiographic appearance and hemodynamic performance of this valve by means of echocardiography. METHODS: The QMV was implanted in 22 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not deemed suitable for repair. Echocardiography was performed pre-operatively, and at one and three months postoperatively. Transthoracic echocardiography (TTE) was used to monitor mean instantaneous pressure gradient as calculated from the long modified Bernoulli equation, cardiac index (CI), pressure half-time and effective orifice area (EOA) using the Hatle and continuity equations. Regurgitation patterns were sought by color Doppler transesophageal echocardiography in all valves intraoperatively following valve implantation, and by TTE in the outpatient clinic at follow up. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), all patients were well and symptomatically improved. At three months postoperatively, the mean pressure gradient ranged from 1.7 to 2.2 mmHg. The EOA was larger using the Hatle as compared with the continuity equation (2.4 +/- 0.7 cm2 versus 1.8 +/- 0.5 cm2, respectively; p < 0.005). Mitral regurgitation was trivial in 77% and mild in 14% of patients at 3 months after surgery; moderate mitral stenosis was noted in one patient. The CI improved significantly postoperatively (p < 0.005), and left ventricular function was maintained. CONCLUSIONS: The hemodynamic performance of this novel prosthesis is favorable. Although follow up is too short to assess durability, it is hoped that the unique design and improved valve preservation technique of this device will enhance long-term durability.

Adult↗
PubMed1999

Exercise-induced hyperkalemia and concentration of Na,K-pumps in skeletal muscle in mitral stenosis: effect of balloon mitral valvotomy.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to examine the effects of balloon mitral valvotomy (BMV) on exercise-induced hyperkalemia, and on changes in the concentration of Na,K-pumps in skeletal muscle, as an exaggerated exercise-induced rise in potassium concentration ([K+]) may contribute to exertional fatigue and breathlessness. METHODS: Eight subjects were evaluated with mitral stenosis (mean age 34 +/- 5.2 years) before, and at two weeks and four months after BMV. Subjects underwent incremental exercise to exhaustion for exercise-induced rise in [K+] and vastus lateralis biopsy for concentration of Na,K-pumps. RESULTS: Mean (+/- SE) valve area increased from 0.89 +/- 0.03 cm2 before to 1.75 +/- 0.05 cm2 after BMV. There was a progressive increase in VO2,max (15.3 +/- 1.6, 17.2 +/- 1.4 and 19.9 +/- 1.9 l/kg/min) at baseline, early after and later after BMV, respectively (p < 0.01). The rise in [K+] with absolute workload fell progressively at early and late follow up post-BMV (p < 0.05), but was unchanged when plotted against percentage of VO2,max to match for relative workload. The concentration of Na,K-pumps was similar to baseline at early follow up (233 +/- 10 versus 228 +/- 15 pmol/g wet weight), but was significantly increased at late follow up after four months (265 +/- 17 pmol/g; p < 0.05). When the relationship between the concentration of Na,K-pumps and the exercise-induced rise in [K+] was studied, a negative correlation was found. However, correlation analysis for the effects of changes in Na,K-pumps on changes in exercise hyperkalemia after BMV was not significant. CONCLUSIONS: The progressive reduction in exercise-induced rise in [K+] after BMV may contribute to the progressive improvement in exercise performance. The increased concentration of Na,K-pumps in skeletal muscle may assist in this improvement, and emphasizes the importance of peripheral adaptations in clinical improvement after BMV.

Adult↗
PubMed1999

The quadrileaflet mitral valve: follow-up in rheumatic heart disease.

This prospective study evaluated the clinical performance of a novel stentless quadrileaflet bovine pericardial mitral valve implanted at one center since December 1996. After giving informed consent, patients were included in the study if they required isolated mitral valve replacement. All underwent comprehensive clinical evaluation, as well as transthoracic M-mode, two-dimensional and Doppler (pulsed, continuous, and color) echocardiography preoperatively and postoperatively at 1 month, 3 months, and annually thereafter. Mitral valve area was derived by planimetry, the pressure half-time method, and the continuity equation. The degree of mitral regurgitation was semi-quantitated using color Doppler. In all 38 patients with rheumatic valvular heart disease (mean age 35+/-13 years) were monitored for 13.8+/-7.5 months (range, 1 to 29 months). All but three patients are alive and symptomatically improved (functional New York Heart Association class I or II). One valve was explanted because of early prosthetic valve endocarditis. There were no episodes of thromboembolism or anticoagulation-related hemorrhage. Left ventricular function was maintained with increased cardiac output and low transmitral pressure gradients. The mitral valve area was larger when measured by pressure half-time and planimetry than by the continuity equation (P<.05). In an independent clinical evaluation of a subset of 30 patients, mitral stenosis was considered absent in 33%, mild in 30%, mild to moderate in 26%, and moderate in 10% of cases. No or less than or equal to mild mitral regurgitation was noted in the majority of patients postoperatively, both clinically and echocardiographically. We are encouraged by the clinical performance of the quadrileaflet mitral valve and with patient outcome. Long-term follow-up data are needed to assess durability.

Adult↗
PubMed1998

Avoiding fundamental reform: current cost containment strategies in Canada.

Provincial governments in Canada are trying very hard to contain and possibly reduce health care expenditure. The wide ranging effort and frequent announcements of yet another cost cutting measure, including deinsurance, stand in marked contrast to the complacency of earlier periods. This activist and serious effort to reform the system is certainly welcome, yet the reforms are not adequate and ignore some fundamental and structural problems of Canada's health care system. Health care reform must do one or more of three things, i.e., improve efficiency, effectiveness, and/or equity of the system. Many cost-cutting measures in Canada achieve none of these objectives and merely postpone costs to a later time or shift the burden on to the sick. Fundamental health reforms include the incentive systems influencing physician behavior and choices; efficiency gains via manpower substitution; more effective control over the supply and distribution of medical manpower; and changes in the organization and design of health care delivery systems. But these fundamental reforms are not being pursued in Canada even though this is an opportune time for such reforms. Also discussed is the potential for and problems associated with managed and/or public sector competition. This article is essentially a critical review of current cost containment efforts in Canada.

Canada↗
PubMed1997

The role of consumers in health care decision making.

This paper focuses on the results of a survey of chief executive officers and consumer board members of Ontario hospitals and community health centres regarding the role of consumers in health care decision making. The opinions of both the chief executive officer and consumer board member respondents were elicited regarding the value of consumer input in decision making for the organizations studied. Results indicate that consumer board members feel that their input into organizational decision making is valued, chief executive officers value the input of consumers, and consumer involvement in decision making is increasing. More women are now involved on boards of the organizations studied, but visible minority representation remains low on hospital boards. Consumer board members feel that their decision making is influenced by providers on the board.

Attitude of Health Personnel↗