Telemedicine in Greenland--from the early beginnings to the making of a business plan

Greenland has a geography and demography that make telemedicine a logical choice when planning a future public health service. Telemedicine was introduced in 1994. Although everybody considered it to be a good idea, it took five years to move from initial enthusiasm to politicians and officials committing the necessary resources. Over such a long period, there is a risk that good ideas will become neglected, although, where resources are limited, it is useful as a time in which to select the best of the new ideas. We have certainly gained a great deal of experience which we will use if and when, over the next two years, we have to argue for an extension of our business plan.     

Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa: does climate matter?

The geographical ranges of most species, including many infectious disease agents and their vectors and intermediate hosts, are assumed to be constrained by climatic tolerances, mainly temperature. It has been suggested that global warming will cause an expansion of the areas potentially suitable for infectious disease transmission. However, the transmission of infectious diseases is governed by a myriad of ecological, economic, evolutionary and social factors. Hence, a deeper understanding of the total disease system (pathogens, vectors and hosts) and its drivers is important for predicting responses to climate change. Here, we combine a growing degree day model for Schistosoma mansoni with species distribution models for the intermediate host snail (Biomphalaria spp.) to investigate large-scale environmental determinants of the distribution of the African S. mansoni-Biomphalaria system and potential impacts of climatic changes. Snail species distribution models included several combinations of climatic and habitat-related predictors; the latter divided into “natural” and “human-impacted” habitat variables to measure anthropogenic influence. The predictive performance of the combined snail–parasite model was evaluated against a comprehensive compilation of historical S. mansoni parasitological survey records, and then examined for two climate change scenarios of increasing severity for 2080. Future projections indicate that while the potential S. mansoni transmission area expands, the snail ranges are more likely to contract and/or move into cooler areas in the south and east. Importantly, we also note that even though climate per se matters, the impact of humans on habitat play a crucial role in determining the distribution of the intermediate host snails in Africa. Thus, a future contraction in the geographical range size of the intermediate host snails caused by climatic changes does not necessarily translate into a decrease or zero-sum change in human schistosomiasis prevalence.     

Accuracy and precision of MR velocity mapping in measurement of stenotic cross-sectional area,flow rate,and pressure gradient

Reliability of magnetic resonance (MR) velocity mapping to assess severity of stenosis was assessed in vitro. Steady flow at different flow rates through five stenoses with a central orifice area ranging from 17 to 176 mm² was measured with velocity mapping performed perpendicular to the stenotic jet. Besides determination of the stenotic cross-sectional area and flow rate, the pressure gradient was calculated with the modified Bernoulli equation and compared with manometer measurements. Cross-sectional areas were measured with an accuracy of ?76%, a precision of ?91%, and an error of ?19 mm². Flow rates had an accuracy of ?72%, a precision of ?94%, and an error of ?1.4 L/min. The modification of the Bernoulli equation limited its reliability to stenoses with areas of 35-113 mm². Pressure gradients were calculated with an accuracy of ?80%, a precision of ?88%, and an error of ?15 mm Hg. The method was applied in a single patient with aortic stenosis and gave estimates that agreed with those obtained by heart catheterization.     

INTERACTION BETWEEN CARBAMAZEPINE AND PROPOXYPHENE IN MAN

This investigation was carried out because of a clinical suspicion of drug interaction between Propoxyphene (PRX) hydrochloride and Carbamazepine (CBZ). Seven out-patients, six suffering from epilepsy and one from trigeminal neuralgia, treated with CBZ alone or in combination with phenobarbitone, received PRX hydrochloride capsules, 65 mg three times a day. Two patients stopped the PRX intake after 2 days due to severe side effects. Three of the remaining patients had symptoms and signs of drug intoxication. Blood samples were examined by thin-layer chromatography. A marked increase (45-77 per cent) in CBZ plasma level was found in all patients on combined treatment of CBZ and PRX. There were no significant changes in CBZ-10,11-epoxide level. The results suggest an inhibition of CBZ metabolism when CBZ and PRX are administered simultaneously.     

Prevalence of malocclusion in relation to premature loss of primary teeth

The influence of premature extraction of primary teeth. The influence of the site of extraction was analyzed by studying the frequency of malocclusion in the group of children with extraction in the mandible or maxilla only. It was found that early loss of primary teeth would result in an increased frequency of sagittal, vertical as well as transversal malocclusion. As a consequence the need for treatment would increase significantly by early extraction of primary teeth. Whereas extraction in the maxilla would tend to result in need for extraction of permanent teeth; extraction in the mandible would often lead to need for orthodontic treatment of longer duration. On the basis of these findings it could be concluded that maintaining a high standard of dental service for preschool children must be considered good economy, since the need for premature extractions is reduced.     

The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice

To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared to controls. Many of them were previously described to be involved in endocrine development and function. Among the genes not previously characterized were Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and the Iroquois-type homeobox gene Irx1, the latter was selected for further investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1 and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon-, but not insulin- or somatostatin-producing cells in mice and chicken. These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of alpha-cell-specific gene expression.     

Coccygeal Movement Test: An Objective,Non-Invasive Test for Localization of the Pelvic Floor Muscles in Healthy Women

Objective

To evaluate the use of palpation of the coccyx (the coccygeal movement test, CMT) as a possible objective screening tool for the assessment of adequate localization of the pelvic floor muscles (PFMs).

Subjects and Methods

Twenty-four healthy female volunteers, known to be able to locate their PFMs, were given instructions (allocated at random) to perform a ‘correct contraction’, ‘straining’ or ‘nothing’ when examined by six independent assessors using the CMT. The assessors were blinded to the instructions and to the test results recorded by other assessors. Data were available for 137 observations, and these were dichotomized into either ‘able to contract’ (‘correct contraction’) or ‘not able to contract’ (‘straining’ or ‘nothing’). This information was used to calculate the sensitivity, specificity and positive and negative predictive values for the CMT.

Results

The CMT correctly identified 56/58 observations when women did not perform the contraction of the PFMs compared to 61/79 observations when they did. Hence, the sensitivity and specificity were 97 and 77%, respectively.

Conclusion

This study showed that the CMT was a useful test to identify women who were able to localize their PFMs compared to those who were not, making it a potentially useful initial screening test in structured training programmes for the PFMs.Key Words: Pelvic floor, Incontinence, Coccygeal movement test, Pelvic floor muscle training     

Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway

We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.     

An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma.

PURPOSE: Human interleukin-21 (IL-21) is a pleiotropic class I cytokine that activates CD8(+) T cells and natural killer cells. We report a phase 1 study of recombinant human IL-21 in patients with surgically incurable metastatic melanoma. The primary objective was to investigate safety and tolerability by determining dose-limiting toxicity (DLT). The secondary objectives were to identify a dose response for various biomarkers in the peripheral blood, estimate the minimum biologically effective dose, determine the pharmacokinetics of IL-21, determine if anti-IL-21 antibodies were induced during therapy, and measure effects on tumor size according to Response Evaluation Criteria in Solid Tumors. EXPERIMENTAL DESIGN: Open-label, two-arm, dose escalation trial of IL-21 administered by i.v. bolus injection at dose levels from 1 to 100 microg/kg using two parallel treatment regimens: thrice weekly for 6 weeks (3/wk) or three cycles of daily dosing for 5 days followed by 9 days of rest (5+9). RESULTS: Twenty-nine patients entered the study. IL-21 was generally well tolerated and no DLTs were observed at the 1, 3, and 10 microg/kg dose levels. In the 3/wk regimen, DLTs were increased in alanine aminotransferase, neutropenia, and lightheadedness with fever and rigors. DLTs in the 5+9 regimen were increased in aspartate aminotransferase and alanine aminotransferase, neutropenia, fatigue, and thrombocytopenia. The maximum tolerated dose was declared to be 30 microg/kg for both regimens. Effects on biomarkers were observed at all dose levels, including increased levels of soluble CD25 and up-regulation of perforin and granzyme B mRNA in CD8(+) cells. One partial tumor response observed after treatment with IL-21 for 2 x 6 weeks (3/wk) became complete 3 months later. CONCLUSIONS: IL-21 is biologically active at all dose levels administered and is generally well tolerated, and phase 2 studies have commenced using 30 microg/kg in the 5+9 regimen.