A severe form of Noonan syndrome and autosomal dominant café-au-lait spots – evidence for different genetic origins

Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype–phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed.
Methods: Mutation analyses of candidate genes, PTPN11 , NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing.
Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes.
Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.     

The tuberculosis challenge in a rural South African HIV programme

Background  

South Africa remains the country with the greatest burden of HIV-infected individuals and the second highest estimated TB incidence per capita worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB incidence and an emerging epidemic of drug-resistant tuberculosis.     

Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa

Background  

To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population.     

A clinical evaluation of the hearing disability and handicap scale in men with noise induced hearing loss

During the last 30 years several hearing disability and handicap questionnaires have been designed and used for clinical purposes. The present study includes a review of the most frequently used scales. The aim of the present study was to evaluate the reliability and validity of the Hearing Disability and Handicap Scale (HDHS), which is a shortened and modified version of the Hearing Measurement Scale. Correlations between the Hearing Handicap and Support Scale, the Communication Strategy Scale from the Communication Profile of the Hearing Impaired, pure tone audiometry and speech recognition scores in noise were analysed. Data from 168 men with noise induced hearing loss of different degrees was obtained. Also a test-retest was conducted. The disability section of the HDHS seemed accurate but offered no improvement of prediction compared to previous scales. Even though the reliability of the handicap section was sufficient, its validity and clinical use is discussed and suggestions about improvements given. Since standardised scales are necessary if results are to be compared worldwide, guidelines regarding the clinical use and benefit of hearing disability and handicap scales are required.     

Dopamine D3 and D4 receptor antagonists in the treatment of schizophrenia

The findings that dopamine D3 and D4 receptors are highly expressed in limbic and cortical areas (D4 more than D3), and the fact that the atypical drug clozapine has preferential affinity for the D4 receptors have suggested an involvement of these receptors in schizophrenia. Subsequently, many pharmaceutical companies have pursued the approach of developing selective dopamine D3 or D4 antagonists as potential antipsychotics. This review will discuss the current status of selective dopamine D3 and D4 receptor antagonists for the treatment of schizophrenia.     

Living in the paddies: a social science perspective on how inland valley irrigated rice cultivation affects malaria in Northern Côte d'Ivoire

The potential impact of irrigated agriculture on water‐related vector‐borne diseases has been an increasing source of concern for researchers from the bio‐medical sector. While most research on the potential impacts of irrigation on the health of local populations focuses on vector densities, levels of exposures, health services and technologies (prophylaxis, mosquito nets), we argue that it is essential to enlarge the scope of investigation and consider the complex mechanisms by which factors such as agriculture‐generated changes in ecosystems, gender repositioning in the family organization as a result of access to new crops, and production activities combine together in increasing disease risks and producing new scenarios in the management of disease. This paper presents the results of an investigation of how transformations induced on the local society by the intensification of inland valley irrigated rice cultivation influence malaria health care systems and modulate risks to the health of local populations, within well‐defined geographical boundaries in northern Côte d'Ivoire. Our results indicate that socio‐economic transformations and gender repositioning induced, or facilitated, by the intensification of inland valley irrigated rice cultivation lead to a reduction of the capacity of women to manage disease episodes, contributing therefore to increase malaria incidence among farming populations.     

Cost-utility analysis of patient care in children with meningeal signs

OBJECTIVES: We designed a model of diagnostic and therapeutic interventions applied in children with meningeal signs. Using this model, we determined in a cost-utility analysis the consequences for society of different diagnostic strategies in terms of quality-adjusted life-years (QALYs) and costs. METHODS: Data were used from 360 children (0.1-15 years) visiting the pediatric emergency department of the Sophia Children's Hospital Rotterdam, The Netherlands (1988-98) with meningeal signs. Model inputs included probabilities of meningitis and adverse outcome, QALYs for years lived with long-term sequelae, and costs of tests and treatments. Mean outcome measures were costs and effects of diagnostic and therapeutic interventions in children suspected of bacterial meningitis, key determinants of the model outcomes, and evaluation of alternative diagnostic strategies and two vaccination programs in an analysis. RESULTS: The population comprised 99 children with bacterial meningitis (adverse outcome in 10), 36 with serious other bacterial infections, and 225 with self-limiting diseases. Key determinants were the risk of bacterial meningitis or sequelae, costs of treatment, and long-term morbidity. Minimizing lumbar punctures and empirical treatments using a diagnostic decision rule, without missing a single case of meningitis, was a dominant strategy to actual practice. Vaccination strategies of Streptococcus pneumoniae and Neisseria meningitidis resulted in our model in incremental cost-utility ratios of 401,965 Euro dollar ([symbol: see text])/QALY and [symbol: see text]22,635/QALY, respectively. CONCLUSIONS: Costs of long-term morbidity of bacterial meningitis largely outweigh diagnostic and treatment costs. Modeling interventions in children at risk of bacterial meningitis should include long-term consequences in terms of costs and QALYs.