Subclinical course of adult visceral Niemann–Pick type C1 disease. A rare or underdiagnosed disorder?

Summary  We present the third case of Niemann–Pick disease type C without neurological symptoms. The patient was a 53-year-old woman without significant prior health problems who died of acute pulmonary embolism. Autopsy findings of hepatosplenomegaly, lymphadenopathy and ceroid-rich foam cells raised the suspicion of the visceral form of acid sphingomyelinase deficiency (Niemann–Pick disease type B; NPB) or a much rarer disorder, variant adult visceral form of Niemann–Pick disease type C (NPC). To verify the histopathological findings, SMPD1, NPC1 and NPC2 genes were analysed. Two novel sequence variants, c.1997G>A (S666N) and c.2882A>G (N961S) were detected in the NPC1 gene. No pathogenic sequence variants were found either in the SMPD1 gene mutated in NPB or in NPC2 gene. The pathogenicity of both NPC1 variants was supported by their location in regions important for the protein function. Both variations were not found in more than 300 control alleles. Identified sequence variations confirm the diagnosis of the extremely rare adult visceral form of Niemann–Pick disease type C, which is otherwise dominated by neurovisceral symptoms. Although only three patients have been reported, this (most probably underdiagnosed) form of NPC should be considered in differential diagnosis of isolated hepatosplenomegaly with foam cells in adulthood. Electronic supplementary material  Supplementary material is available for this article at     

Light emitting diodes for auramine O fluorescence microscopic screening of Mycobacterium tuberculosis.

We describe the simple adaptation of a standard fluorescent microscope for illumination using a 'Royal Blue' Luxeon light emitting diode (LED) and demonstrate that this form of illumination is suitable for the detection of auramine O stained Mycobacterium spp. The low cost, low power consumption, safety and reliability of LEDs makes them attractive alternatives to mercury vapour lamps.     

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.     

Successful closure of spontaneous esophageal perforation (Boerhaave's syndrome) by endoscopic clipping.

Endoscopic clips have been used mainly for control of gastrointestinal (GI) bleeding and occasionally for closure of GI perforations. However, closure of spontaneous esophageal perforation (Boerhaave's syndrome) by clipping has not been reported. We described successful non-surgical closure of spontaneous esophageal perforation by endoscopic clipping in a patient with bilateral pyopneumothorax and septicemia.     

The fist model for nasal packing.

Epistaxis is a common ear, nose and throat emergency. A variety of nasal packs are available to control the bleeding by tamponade. Training of junior doctors to insert nasal packs is difficult when dealing with a bleeding patient. We discovered a readily available and simple model to enable trainees to learn the method of nasal packing.     

Increased incidence of Lyme borreliosis in southern Sweden following mild winters and during warm, humid summers

The aim of the present study was to investigate the long-term incidence rate of Lyme borreliosis and, additionally, to determine whether a correlation exists between climatic factors and summer-season variations in the incidence of Lyme borreliosis. Climatic variability acts directly on tick population dynamics and indirectly on human exposure to Lyme borreliosis spirochetes. In this study, conducted in primary healthcare clinics in southeastern Sweden, electronic patient records from 1997–2003 were searched for those that fulfilled the criteria for erythema migrans. Using a multilevel Poisson regression model, the influence of various climatic factors on the summer-season variations in the incidence of erythema migrans were studied. The mean annual incidence rate was 464 cases of erythema migrans per 100,000 inhabitants. The incidence was significantly higher in women than in men, 505 and 423 cases per 100,000 inhabitants, respectively (p<0.001). The summer-season variations in the erythema migrans incidence rate correlated with the monthly mean summer temperatures (incidence rate ratio 1.12; p<0.001), the number of winter days with temperatures below 0°C (incidence rate ratio 0.97; p<0.001), the monthly mean summer precipitation (incidence rate ratio 0.92; p<0.05), and the number of summer days with relative humidity above 86% (incidence rate ratio 1.04; p<0.05). In conclusion, Lyme borreliosis is highly endemic in southeastern Sweden. The climate in this area, which is favourable not only for human tick exposure but also for the abundance of host-seeking ticks, influences the summer-season variations in the incidence of Lyme borreliosis.     

The Cys allele of the DRD2 Ser311Cys polymorphism has a dominant effect on risk for schizophrenia: evidence from fixed- and random-effects meta-analyses.

Previously we derived independent estimates of the effect of the dopamine D2 receptor (DRD2) Ser311Cys polymorphism on risk for schizophrenia using fixed- and random-effects meta-analyses. Both analyses identified a significant association between the Cys allele and schizophrenia, but neither included all available data. Furthermore, genotype data were not evaluated in either analysis, thus precluding any determination of the mode of inheritance. The present study was conducted to resolve discrepancies between the existing meta-analyses, and provide more comprehensive and accurate estimates of the nature and magnitude of the influence of the Ser311Cys polymorphism on risk for schizophrenia. All discrepancies between the two sets of previously meta-analyzed studies were identified and resolved to the mutual satisfaction of the authors, and the final dataset was analyzed independently by fixed- and random-effects meta-analyses. A total of 27 samples, comprising 3,707 schizophrenia patients and 5,363 control subjects, were included in the analyses of allelic association, while smaller numbers of studies and subjects were included in each of the genotypic association analyses. A significant effect of the Cys allele was observed under both fixed-effects (odds ratio [OR] = 1.4; P = 0.002) and random-effects (OR = 1.4; P = 0.007) models. Cys/Ser heterozygotes were at elevated risk for schizophrenia when compared to Ser/Ser homozygotes (fixed- and random-effects OR = 1.4, p(s) or= 0.948). There was no evidence of heterogeneity, excessive influence of any single study, or publication bias in any of the analyses, suggesting that the effect of this DRD2 polymorphism on schizophrenia risk is reliable and uniform across populations, and our estimates of its magnitude are robust and accurate.