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     

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.     

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.     

Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

Duodenogastric reflux after choledochoduodenostomy

Duodenogastric reflux (DGR) has been implicated in several disease processes. The present study was carried out to document the incidence and evaluate the clinical significance of DGR after choledochoduodenostomy (CDD). A total of 13 patients who had undergone cholecystectomy with a standard side-to-side CDD for choledocholithiasis or chronic pancreatitis were studied by symptom evaluation, scintigraphy, endoscopy, and gastric mucosal histology at least 6 months after surgery. The scintigraphic findings were then compared with those of 10 patients who had undergone cholecystectomy alone. Only two patients (15%) had mild dyspeptic symptoms. The incidence of DGR after CDD was 69% compared to 20% in the cholecystectomy alone group (P < 0.05). In the majority of patients the DGR was only mild to moderate and the severity correlated well with the degree of endoscopic gastritis, but not with the clinical symptoms or histological findings. These results indicate that while CDD is associated with a high incidence of DGR, its occurrence does not produce significant clinical symptoms.     

APPRAISAL OF SURGICAL AND ENDOSCOPIC MANAGEMENT OF CHOLEDOCHOLITHIASIS

One hundred and ten patients with common bile duct (CBD) stones were treated in the Department of Surgical Gastroenterology at SGPGIMS, Lucknow, India between January 1989 and December 1992. The primary modality of treatment was surgery in 62 patients (group I) and endoscopic sphincterotomy (ES) in 48 (group II). The two groups were well matched with respect to clinical features and presence of medical risk factors. Surgical clearance of CBD stones was achieved in 58 patients (93.5%; group Ia). Four patients (7%) had retained stones following surgery (group Ib). In group II, the CBD was cleared by endoscopic means in 20 out of 48 patients (42%) and was categorized into group IIa. In the remaining patients ES was followed by CBD exploration (group IIb). Significantly higher morbidity was seen in patients needing CBD surgery following attempted endoscopic clearance, because of ES-related complications, such as bleeding, cholangitis, septicaemia and numerous others. Use of ES to treat CBD stones on a routine basis was therefore not found to be any better than one-time surgical exploration.     

Effect of N-nitrosomethylbenzylamine on nasal mucosa in rats.

N-nitrosomethylbenzylamine (NMBA) is one of the most potent organ-specific carcinogens routinely used in rat esophageal tumorigenesis. The aim of the study was to evaluate NMBA effect on nasal mucosa, one of the non-target organs. NMBA was administered subcutaneously to 20 male albino rats of Wistar strain for 5 weeks (0.5mg/kg/dose; three doses/week). The experiment was terminated on week 22. In each case, seven standard frontal sections of the nose were taken after fixation for assessment of all the parts of the nasal mucosa. Microscopic examination revealed one small squamous cell papilloma located on the ventro-lateral surface of the left superior nasal concha, one focus on simple hyperplasia and two foci of squamous epithelium dysplasia within the mucosa covering nasal vestibule near the respiratory part of the nasal cavity. Furthermore, statistically significant increase of proliferation activity in both lesional and non-lesional nasal squamous epithelium in NMBA-exposed animals was also found. These phenomena could be potentially induced by carcinogen exposure.     

Borrelia burgdorferi sensu stricto in yellow-necked mice and feeding Ixodes ricinus ticks in a forest habitat of west central Poland

Wild rodents and the subadult Ixodes ricinus (L.) ticks infesting them were examined for the presence of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner s.l. in a sylvatic habitat in west central Poland during May-September 2002. In total, 818 feeding ticks were recovered from 73 infested yellow-necked mice, Apodemus flavicollis Melchior; in addition, bank voles, Clethrionomys glareolus Schreber, were rarely captured and proved to be weakly parasitized. Only 2.7% of A. flavicollis and 2.2% of 320 engorging larvae were polymerase chain reaction (PCR) positive for the bacterium. All spirochete-PCR-positive samples yielded exclusively B. burgdorferi s.s. This genospecies was also the most prevalent in questing nymphs and accounted for 87.5% of the total number of Borrelia infections in nymphal ticks collected during May and June 2 yr later. The presence of the same genospecies both in naturally engorged larvae and blood-positive animals as well as the high predominance of B. burgdorferi s.s. in questing nymphs strongly differs from most study sites investigated in Europe. This unique pattern of Borrelia-diversity in both rodents and ticks seems to be determined by highly site-specific host vertebrate cenosis, and yellow-necked mice are involved in the maintenance of B. burgdorferi s.s. in the forest habitat. However, the transmission efficiency of this spirochete from the mice to the I. ricinus vector seems to be very low. The research provides additional information on the complexity of B. burgdorferi s.l. ecology in Europe, pointing to the importance of the local host community.     

Raman spectroscopic study of glutaraldehyde-stabilized collagen and pericardium tissue

For the first time, Raman spectroscopy has been employed to investigate formation of cross-links in collagen and porcine pericardium tissue upon glutaraldehyde (GA) treatment. GA treatment causes a very high fluorescence background, which overlaps Raman bands. It has been found that short fixation time, i.e. 2 h, reduces background radiation significantly, providing new possibilities for studying changes in molecular structure of collagen upon GA modification. The observed changes in position and intensity of Raman bands allowed us to recognize different types of GA-collagen interactions. Strong spectral evidence has been found for the peptide contribution to the formation of the GA-collagen cross-links and for the formation of secondary amines via Schiff base intermediates, and pyridinium-type cross-links. The results also revealed that different hydration levels and a more complex structure of intact tissue in comparison to collagen preparation strongly influence the formation of a GA cross-linking network, e.g. ether-type bond is preferred to form in a less hydrated collagen preparation. Our results have shown that GA treatment causes an increase in water content of pericardium tissue and collagen.