Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins

We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time.     

Neonatal outcome in a Danish national cohort of 3438 IVF/ICSI and 10,362 non-IVF/ICSI twins born between 1995 and 2000

BACKGROUND: In Denmark, one-third of twin pregnancies are the result of IVF/ICSI treatment. Limited data on neonatal outcome in IVF/ICSI twins are available in the literature. METHODS: A register study was conducted on neonatal morbidity and mortality in a complete national twin cohort including all 3438 (3393 live-born) IVF/ICSI and 10,362 (10,239 live-born) non-IVF/ICSI twins born between 1995 and 2000. Twins were identified in the National Medical Birth Registry and dichotomized into IVF/ICSI and non-IVF/ICSI by cross-reference with the Danish IVF Registry. Data on neonatal morbidity and mortality were retrieved from the Danish Patient Registry and the Danish Registry of Causes of Deaths. In order to exclude monozygotic twins, sub-analyses on unlike-sex twins were conducted. RESULTS: A birth weight discordance of >20% was observed in 20.6% of IVF/ICSI versus 15.7% of control twin pairs (P < 0.001). The risk of discordant birth weight >20% was OR 1.29 (95% CI 1.04-1.58) in unlike-sex IVF/ICSI twins versus control twins. The risk of delivery at <37 completed weeks and birth weight <2500 g was similar in the two cohorts; however, in unlike-sex IVF/ICSI versus control twins the risk of delivery at <37 weeks and birth weight <2500 g was OR 1.22 (95% CI 1.09-1.38) and OR 1.25 (1.11-1.40) respectively. After stratification for maternal age and parity, these risks disappeared. IVF/ICSI twins carried a higher risk of admittance to a neonatal intensive care unit (NICU) than control twins (OR 1.18, 95% CI 1.09-1.27), and this was even more pronounced in unlike-sex twins [OR 1.34 (95% CI 1.19-1.51)]. No differences were observed in malformation or mortality rates between the two cohorts. CONCLUSIONS: Despite higher birth weight discordance and more NICU admissions among IVF/ICSI twins, neonatal outcome in IVF/ICSI twins seems to be comparable with that of non-IVF/ICSI twins, when only dizygotic twins were considered in the comparisons.     

Ultrastructure of the Kidney in Acute Interstitial Nephritis

Fifteen percutaneous renal biopsies from patients with acute renal failure due to acute interstitial nephritis (AIN), in almost all cases due to drugs, were studied by electron microscopy. Differential counting of interstitial cells showed an average of 69% lymphocytes (small and large) and 11 % macrophages. Plasma cells and eosinophils were comparatively rare. The infiltrate resembled that of acute rejection, suggesting a cellular hypersensitivity reaction. Proximal and distal tubules were severely affected focally. Migration of lymphocytes through the tubular basement membrane of otherwise well-preserved tubules was considered to be the first phase. Other tubules showed extreme thinning of the tubular basement membrane, with still intact cellular walls. Rupture of the tubular basement membrane and necrotic disintegration of tubular epithelial cells are probably late phenomena. The non-necrotic tubules displayed severe reduction of proximal brush border and proximal as well as distal tubular basolateral infoldings. Focal tubular disintegration leading to tubular block and/or backleak as well as decrease of proximal tubular sodium resorption leading to a decreased glomerular filtration (a mechanism probably also acting in ischemic acute renal failure) may all be factors responsible for the acute renal failure in AIN.     

Sexual Contact as Risk Factor for Campylobacter Infection,Denmark

Campylobacteriosis is a disease of worldwide importance, but aspects of its transmission dynamics, particularly risk factors, are still poorly understood. We used data from a matched case-control study of 4,269 men who have sex with men (MSM) and 26,215 controls, combined with national surveillance data on Campylobacter spp., Salmonella spp., and Shigella spp., to calculate matched odds ratios (mORs) for infection among MSM and controls. MSM had higher odds of Campylobacter (mOR 14, 95% CI 10–21) and Shigella (mOR 74, 95% CI 27–203) infections, but not Salmonella (mOR 0.2, 95% CI 0–13), and were less likely than controls to have acquired Campylobacter infection abroad (χ² = 21; p<0.001). Our results confirm that sexual contact is a risk factor for campylobacteriosis and also suggest explanations for unique features of Campylobacter epidemiology. These findings provide a baseline for updating infection risk guidelines to the general population.     

Scleroderma renal crisis

Scleroderma renal crisis (SRC) is a rare but life-threatening complication of systemic sclerosis (SSc) characterized by malignant hypertension and acute kidney injury. Historically, SRC was the leading cause of death in SSc. However, with the advent of angiotensin converting enzyme (ACE) inhibitors, mortality rates have decreased significantly. Nevertheless, one-year outcomes remain poor, with over 30% mortality and 25% of patients remaining dialysis-dependent. There is an urgent need to improve early recognition and treatment, and to identify novel treatments to improve outcomes of SRC. In this chapter, the clinical features, classification, pathophysiology, differential diagnosis, management and outcomes of SRC are presented. Specific issues relating to pregnancy, prophylactic ACE inhibition and management of essential hypertension are also discussed.     

Electromagnetic shock wave lithotripsy of gallbladder stones in vitro: the role of different stone characteristics and treatment variables

From 40 sets of five human gallstones obtained at cholecystectomy, four stones were subjected to either 125/250 (maximum generator output) or 250/500 (half maximum generator output) electromagnetic shock waves (treatments I/II and III/IV, respectively); the fifth stone was used for computed tomography (CT) and chemical analysis. Overall, 130 (81%) of 160 stones fragmented, including 72 (45%) adequately (fragments less than or equal to 5 mm). For the treatments I, II, III, and IV the overall fragmentation rates were 80%, 95%, 70%, and 80%, respectively. The corresponding percentages of adequate fragmentation ( less than or equal to 5 mm) were 38%, 70%, 30%, and 42%, respectively. The best results were thus obtained after application of 250 shock waves (maximum generator output; treatment II). Pure cholesterol stones (p less than 0.01), stones with a mean CT density less than or equal to 110 HU (p less than 0.001), and stones with a calcified rim (p < 0.05) fragmented significantly better, but adequate fragmentation ( less than or equal to 5 mm) was significantly determined by stone weight and diameter (p less than 0.001), bilirubin content (p less than 0.02), and calcium content (p less than 0.05). A weight greater than 500 mg and a diameter > 10 mm could be defined as stone characteristics with significant negative predictors of adequate fragmentation. However, because the experimental conditions in this in vitro study did not completely simulate clinical settings for various reasons, these observations must be interpreted accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new respiratory rate monitor: development and initial clinical experience

The need for continous, noninvasive, and reliable respiratory rate monitoring during recovery from general anesthesia has long been recognized. Alternative principles can be grouped into those detecting the respiratory effort, and those detecting the actual result, i.e. the respiratory gas flow. The second category is of greatest interest for patient monitoring. In this paper, we report the development and initial clinical experience with a new acoustic air-flow sensor. By differential, multipoint detection of the air-flow in the mouth and nose region, the sensor can easily discriminate against different kinds of interference, including motion arterfacts. The sensor is nonexpensive, rugged, simple to apply, and inherently safe. An instrument with continous display of respiratory rate, and an audiovisual apnea alarm has been designed and built.The complete system has been tested on patients during recovery after general anesthesia. In 16 patients, the respiratory rate displayed by the instrument has been correlated against that visually observed. A good correlation was obtained. Minor discrepancies can be explained from the fact that visual observation corresponds to the respiratory effort, whereas the sensor detects the actual air flow. In 12 patients, 24 hour simultaneous recordings were made of respiratory rate with the new sensor, with simultaneous recording of the oxygen saturation and the heart rate with a pulse oximeter. It was found that the new sensor reliabley recorded respiratory depression and apnea. Such events may in some patients be as frequent as one incident per hour. One case of Ondine's curse provided clear evidence that pulse oximetry has a low sensitivity to respiratory disorders.