The 48-hour tetrahydrobiopterin loading test in patients with phenylketonuria: evaluation of protocol and influence of baseline phenylalanine concentration.

BACKGROUND: The 24- and 48-hour tetrahydrobiopterin (BH4) loading test (BLT) performed at a minimum baseline phenylalanine concentration of 400 µmol/l is commonly used to test phenylketonuria patients for BH4 responsiveness. This study aimed to analyze differences between the 24- and 48-hour BLT and the necessity of the 400 µmol/l minimum baseline phenylalanine concentration. METHODS: Data on 186 phenylketonuria patients were collected. Patients were supplemented with phenylalanine if phenylalanine was <400 µmol/l. BH4 20mg/kg was administered at T = 0 and T = 24. Blood samples were taken at T=0, 8, 16, 24 and 48 h. Responsiveness was defined as ≥ 30% reduction in phenylalanine concentration at ≥ 1 time point. RESULTS: Eighty-six (46.2%) patients were responsive. Among responders 84% showed a ≥ 30% response at T = 48. Fifty-three percent had their maximal decrease at T = 48. Fourteen patients had ≥ 30% phenylalanine decrease not before T = 48. A ≥ 30% decrease was also seen in patients with phenylalanine concentrations <400 µmol/l. CONCLUSION: In the 48-hour BLT, T = 48 seems more informative than T = 24. Sampling at T = 32, and T = 40 may have additional value. BH4 responsiveness can also be predicted with baseline blood phenylalanine <400 µmol/l, when the BLT is positive. Therefore, if these results are confirmed by data on long-term BH4 responsiveness, we advise to first perform a BLT without phenylalanine loading and re-test at higher phenylalanine concentrations when no response is seen. Most likely, the 48-hour BLT is a good indicator for BH4 responsiveness, but comparison with long term responsiveness is necessary.

[Congenital hyperinsulinism in 15 infants, 1981-1999; experiences and new insights]. / Congenitaal hyperinsulinisme bij 15 kinderen, 1981-1999; ervaringen en nieuwe inzichten.

OBJECTIVE: To report on a retrospective study into the diagnostics and treatment of infants with congenital hyperinsulinism (CHI; persistent hyperinsulinemic hypoglycaemia). DESIGN: Retrospective and descriptive. METHOD: The study included all 15 patients diagnosed with CHI at the St Radboud University Medical Centre, the Netherlands, from 1981 until 1999. Data gathered by systematically searching case-notes included: presentation, clinical admission, laboratory results, treatment and follow-up. RESULTS: Four of the 15 infants were macrosomatic; 12 (80%) were presented within 4 days of birth, and the rest after the age of 5 months. Their symptoms were partially aspecific (feeding poorly, lethargy) and partially clear, corresponding to neuroglycopaenia (jitteryness, hypotonia). Nine infants experienced convulsions. The amount of glucose that had to be administered to achieve normoglycaemia (average: 16.9 mg/kg/min) was far above the basal requirement of 4-8 mg/kg/min. Ketone serum and free fatty acid values were lowered during a hypoglycaemic episode, hyperinsulinism was detected after repeated measurements. Five infants responded well to treatment with diazoxide. Ten children underwent subtotal pancreatectomy after which 4 remained normoglycaemic. Three of the 10 children who underwent surgery developed an exocrine pancreas dysfunction. We did not systematically examine neuropsychological development, but in 5 of the 15 children this was clearly disturbed.

Exercise intolerance, muscle pain and lactic acidaemia associated with a 7497G>A mutation in the tRNASer(UCN) gene.

A 13-year-old girl with non-familial exercise intolerance, muscle pain and lactic acidaemia underwent a muscle biopsy for suspected mitochondrial disease. Muscle morphology showed 25% ragged-red fibres and 80% COX-negative staining. Enzymatic activities of mitochondrially co-encoded respiratory chain enzymes (complexes I, III, and IV) were decreased in muscle but normal in cultured skin fibroblasts. mtDNA analysis revealed the presence of the 7497G>A mutation in the tRNASer(UCN) gene, homoplasmic in skeletal muscle and 90% in leukocytes. Analysis of the mother's mtDNA showed 10% heteroplasmy in blood. It may be concluded that the 7497G>A mutation is associated with a muscle-only disease presentation for which high levels of mutated mtDNA are required. Exercise intolerance and muscle pain in otherwise normal children warrants further mitochondrial evaluation.

[World Health Organization strategies "Towards Unity for Health" and the social responsibility of medical schools]. / La stratégie de l'OMS "Vers l'Unité Pour la Santé" et la responsabilité sociale des facultés de médecine.

One may wonder why multiple endeavours conducted worldwide over the last five decades to reform health systems have not achieved their expected outcomes. In light of increasing fragmentation, the current health system must be substituted by a true systems vision along with political will to create a unity of action between the five main stakeholders, namely: policy-makers, health care service managers, professionals and professional associations, academic institutions including medical schools, and civil society. Such synergy can only be established if the partners share the same commitment to core values such as quality, equity, relevance and cost-effectiveness in the health care field. Through its functions of providing education, training, research, and services, the medical school has the potential to induce reflection and stimulate action leading to a more coherent, effective, and equitable health system and policies.

Clinical heterogeneity in patients with mutations in the NDUFS4 gene of mitochondrial complex I.

A comparison of the clinical presentation, disease course and results of laboratory and imaging studies of all patients so far published with a NDUFS4 mutation are presented. This reveals marked clinical heterogeneity, even in patients with the same genotype.

[Influenza A pneumonia]. / Influenza-A-pneumonie.

The majority of influenza cases are not associated with complications. Secondary bacterial pneumonia, commonly caused by Streptococcus pneumoniae or Staphylococcus aureus, is well known to most clinicians. Primary influenza viral pneumonia, characterized by rapidly progressive hypoxia and respiratory insufficiency together with non-consolidating pulmonary infiltrates, has a high mortality rate. In 3 patients, a man aged 74 years, and two neonates aged 11 months and 4 weeks respectively, primary influenza A pneumonia was diagnosed. In the latter two patients the virus was cultivated from sputum. Despite intensive supporting and drug treatment, the first and the last patients died. In view of evolving therapeutic possibilities, notably regarding neuraminidase inhibitors, it is important that clinicians recognize this complication of influenza at an early stage.

Quest for social accountability: experiences of a new health sciences university in Nepal.

CONTEXT: B.P. Koirala Institute of Health Sciences (BPKIHS), a new Health Sciences University in Nepal has taken several steps to respond to the societal needs and has adopted an integrated, partially problem based and community oriented curriculum. OBJECTIVE: The objective of this study was to measure the school's achievements in responding to societal needs. METHODOLOGY: A descriptive cross sectional questionnaire survey (N = 46) of the administrators, faculty, students/residents and the community. The questionnaire included statements on relevance, quality, cost effectiveness and equity in the education, service and research domains of a medical school. The data were analyzed by using WINKS 4.5, a statistical package for Windows. RESULTS: The responders satisfactorily rated BPKIHS. The mean rating (mean 3.11, SD = 1.06) was more than the satisfactory score (3). The responders were satisfied with the education (Mean = 3.26, SD = 1.06) and research (Mean = 3.12, SD = 1.10) but were less satisfied with the service domain (Mean = 2.94, SD = 0.98). The majority believed that the service is based on health care priorities (72%), and includes primary care (80%). A fair proportion felt the need for improvements in quality of care (50%) and cost effectiveness of care (46%). In general the faculty and administrators groups were more satisfied than the community and students/residents groups. CONCLUSION: The study was useful in identifying the school's strengths as well as weaknesses in responding to the societal needs.

Adapting health care institutions and medical schools to societies' needs.

Although societies and the priorities of stakeholders within them differ, four universal values regarding health care exist: quality, equity, relevance, and cost-effectiveness. The first two of these values can be viewed as poles of "the dream axis" and the second two as poles of "the reality axis." Medical schools and other stakeholders can pursue optimal patterns of health care most effectively through partnerships with one another. With regard to improving the health care system, medical schools can be characterized as neutral, reactive, or proactive. A socially responsible medical school perceives the needs of society and reacts accordingly, and a socially accountable school also consults society about priorities and provides evidence of impact of its deeds. A grid for assessing the social accountability of medical schools has been developed. With this grid, a school's activities in education, research, and service are evaluated relative to the four universal values of quality, equity, relevance, and cost-effectiveness of health care; activities also are characterized as "planning," "doing," or "impacting." Assessment can promote greater social accountability of medical schools.

Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia.

The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.

Prospects for change in medical education in the twenty-first century.

With Health for All as a social goal and a reference point, medical schools must create new alliances within the health sector and with other sectors bearing on health. The future role and responsibility of the medical school should reflect the likely essential features of the future health system and the aptitudes that medical practitioners will have to possess. Medical schools should be encouraged not only to shape their educational programs accordingly, but also to devote energy and resources to the considerable task of creating opportunities for this new practitioner. Quality in medical education results from a coordinated effort to ensure relevance and efficiency in the education of future doctors and to ensure these doctors' optimal fit in society. Implicit in the notion of quality is a special consideration for social accountability. A medical school shows social accountability through its commitment to addressing issues, or helping solve problems, identified jointly with society as priorities for both the present and the longer term, in the expectation that the medical school's action will benefit in part the local community and in part the country as a whole or the international community. Indicators of quality in medical education, as well as measurement tools, must be developed and tested in various sociocultural contexts. A taxonomy to assess the social accountability of medical schools is proposed.

The challenge of changing medical education and medical practice.

Fundamental issues are being raised worldwide on the future orientation of health systems. Doctors who have been driving the systems and are seen to be largely responsible for the present situation must now respond. These issues are concerned with equity of access to health care, quality of care, consumer satisfaction, rationing of resources, individual versus community rights, environmental determinants of health, technology assessment, and cost. The search for a new model that integrates all these factors has begun. And if the medical profession is to continue to play an influential role in health policy-making and to be respected by society, it must definitely adapt to the health requirements now being expressed by political decision-makers and health consumers.

Elaboration of a water ichtyologic potential index.

A model has been developed, using physico-chemical data, in order to quantify the quality of surface waters and their ichtyologic potential: the WIPI model (Water Ichtyologic Potential Index). Many physico-chemical parameters, useless if considered individually, can be of practical interest for pisciculture (e.g., an explanation of systematic fish mortalities, elaboration of guidelines for new pisciculture). The water quality is expressed in terms of an eight-step scale that provides a guide evaluation of the ichtyologic potential.

A call for systematic action for changing medical education: reaction of working partners.

How far has medical education been reshaped to meet society's new realities and expectations? More than 40 years have passed since the establishment of the World Health Organization. More than 20 years of the WHO's active work has gone into the educational development of health professionals. And it is now more than 10 years since the Declaration of Alma-Ata, which urged Member States to reorient their health systems so as to provide for more equitable and appropriate services to every citizen on our planet. But the question remains: have there been any significant changes in medical education that reflect these events?