Segmental volvulus of the ileum without malrotation in an infant: A case report

AbstractIntestinal volvulus usually occur secondary to malrotation, and primary segmental volvulus has rarely been reported. A 12-month-old female infant presented with a 3-day history of excessive vomiting. An ultrasonography revealed a “whirlpool sign” in the right upper abdomen, suggesting small bowel volvulus with obstruction. Laparotomy revealed a twisted, viable loop of small bowel in the right upper abdomen, and abnormal adhesions were noted between the distal and mid ileum, with resulting mesenteric narrowing. Attempted mesenteric widening by dissection of the peritoneum overlying the adhesions failed, because of abnormal, taut mesenteric vessels. Subsequent resection of the involved segment cured the patient. Recurrent obstructive symptoms in an infant can be an atypical presentation of segmental volvulus, and segmental volvulus should be included in the differential diagnosis of such cases

Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.

Contains fulltext : 88104.pdf (publisher's version ) (Open Access)BACKGROUND: Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression. METHODS AND RESULTS: We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, -0.0003-0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020-0.061]; P<0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase. CONCLUSIONS: Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation

Lack of association between common genetic variation in endothelial lipase (LIPG) and the risk for CAD and DVT

Low levels of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD) and possibly for deep venous thrombosis (DVT). Endothelial lipase is involved in HDL-C metabolism. Common variants in the endothelial lipase gene (LIPG) have been reported to be associated with HDL-C levels and atherothrombosis, but these findings were not consistent. We determined whether five tagging single nucleotide polymorphisms (SNP) in LIPG were associated with lipid parameters, the risk of CAD and the risk of DVT. We used the prospective case-control study nested in the EPIC-Norfolk cohort (1138 CAD cases, 2237 matched controls) for the initial association study and, subsequently, the ACT study (185 patients with documented DVT, 586 patients in which DVT was ruled out) to replicate our findings regarding DVT risk. In EPIC-Norfolk, we found that the minor allele of one SNP, rs2000813 (p.T111I), was associated with moderately higher HDL-C and apolipoprotein A-I levels, higher HDL particle number and larger HDL size. No variants were associated with CAD risk, but three variants were associated with DVT risk (odds ratios 0.60 [95%CI 0.43-0.84], 2.04 [95%CI 1.40-2.98] and 1.67 [95%CI 1.18-2.38] per minor allele for rs2000813, rs6507931 and rs2097055 respectively, p <0.005 for each). However, the association between LIPG SNPs and DVT risk could not be replicated in the ACT study. Our data support a modest association between the LIPG rs2000813 variant and parameters of HDL metabolism, but no association between common genetic variants in LIPG and CAD or DVT ris

Well-differentiated Pancreatic Neuroendocrine Tumor in a Patient With Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM)

Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM), which is associated with an increased risk for pancreatic ductal adenocarcinoma and melanoma. CDKN2A is somatically inactivated in multiple neoplasms, raising the possibility that, although the data are not conclusive, germline CDKN2A mutation may also impose an increased risk for other neoplasms. We present a patient with a CDKN2A germline mutation (p16-Leiden mutation) and mosaicism for neurofibromatosis type 2, who presented with a small asymptomatic pancreatic lesion, detected during endoscopic ultrasound screening of the pancreas. After resection, the lesion was found to be a well-differentiated pancreatic neuroendocrine tumor (PanNET). Molecular analysis of the tumor showed somatic loss of the second allele, supporting a causal relation of the PanNET to the underlying FAMMM syndrome. Recent data, showing the association between certain single-nucleotide polymorphisms in the CDKN2A gene and an increased incidence for PanNET, further support a role for germline CDKN2A alterations in PanNET risk. We conclude that PanNETs can be a phenotypic expression of FAMMM syndrome. This can have implications for screening and for the diagnosis of pancreatic neoplasms in carriers of germline CDKN2A mutations

Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.

The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1P297S heterozygotes. Lipoproteins from six SR-B1P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed. Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I. The SR-B1P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1.Funding agencies: EUs Sixth Framework Program [037631]; European Union [FP7-603091-2]; CardioVascular Research Initiative [CVON2011-16]; Research Council of South East Sweden [FORSS-3755]; County Council of Ostergotland (C-ALF); Faculty of Health Sciences in Linkoping; Ven</p

Determining efficacy of Monosodium Glutamate for salt reduction inPlain and spiced ‘Poories’ through sensory responses

Palatability is considered as a major determinant of food selection and intake. Umami foods are being employed widely in savory food formulation for its greater potential for enhancing savory taste. In the present investigation, the role of monosodium glutamate (MSG) in salt reduction along with spices was investigated to understand the flavor potentiating effect and synergistic action of MSG. Deep fried unleavened wheat based traditional Indian bread (Poories) was chosen to study the acceptability. Control product was prepared with 2.0% salt. For experimental products, two levels of MSG viz, 75 and 100 mg/100 g and three levels of salt, namely, 1.5, 1.75 and 2.0% were selected. Spices, namely, chili (Capsicum annum L.) cumin (Cuminum cyminum)), pepper (Piper nigrum L) and omum (Trachyspermum ammi)) were incorporated into the product, either as single spice or in combination. The results revealed that the MSG added products were given a higher score for umami flavour in comparison to the control product. In general, MSG added products scored better for flavor in salt reduced products. Results of low sodium poories with single spices and different level of salt indicated that all products prepared with spices were equally liked for the selected sensory characteristics. The products prepared with 1.75% salt obtained highest scores. This is indicative of the flavour enhancing property of MSG. Similarly for products with mixture of spices; salt reduced products were also accepted well. PCA plot revealed the flavor potentiating effect of MSG in salt reduction. Thus it could be said that using MSG and spices combination would be a better option for achieving salt reduction in savory products

Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: A pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials

Background - Torcetrapib, an inhibitor of cholesteryl ester transfer protein, has been shown to increase the cardiovascular event rate despite conferring a significant high-density lipoprotein cholesterol increase. Using data from the Rating Atherosclerotic Disease Change by Imaging with a New CETP Inhibitor (RADIANCE) trials, which assessed the impact of torcetrapib on carotid intima-media thickness (cIMT), we sought to explore potential mechanisms underlying this adverse outcome. Methods and Results - Data from the RADIANCE 1 and 2 studies, which examined cIMT in 904 subjects with familial hypercholesterolemia and in 752 subjects with mixed dyslipidemia, were pooled. Subjects were randomized to either atorvastatin or torcetrapib combined with atorvastatin. Mean common cIMT progression was increased in subjects receiving torcetrapib plus atorvastatin compared with subjects receiving atorvastatin alone (0.0076±0.0011 versus 0.0025±0.0011 mm/y; P=0.0014). Subjects treated with torcetrapib plus atorvastatin displayed higher postrandomization systolic blood pressure and plasma sodium and bicarbonate levels in conjunction with lower potassium levels. The decrease in potassium levels was associated with the blood pressure increase. Markedly, the use of renin-angiotensin-aldosterone system inhibitors tended to aggravate the blood pressure increase. Subjects receiving torcetrapib plus atorvastatin with the strongest low-density lipoprotein cholesterol reduction showed the smallest cIMT progression, whereas subjects with the highest systolic blood pressure increase showed the largest cIMT progression. High-density lipoprotein cholesterol increase was not associated with cIMT change. Conclusions - These analyses support mineralocorticoid-mediated off-target toxicity in patients receiving torcetrapib as a contributing factor to an adverse outcome. The absence of an inverse relationship between high-density lipoprotein cholesterol change and cIMT progression suggests that torcetrapib-induced high-density lipoprotein cholesterol increase does not mediate atheroprotection. Future studies with cholesteryl ester transfer protein inhibitors without off-target toxicity are needed to settle this issue

Incidence and risk factors for acute kidney injury in head and neck cancer patients treated with concurrent chemoradiation with high-dose cisplatin

Background: Three-weekly high-dose cisplatin (100 mg/m2) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Concurrent chemoradiation (CRT) with high-dose cisplatin is associated with significant acute and late toxicities, including acute kidney injury (AKI). The aims of this study were to investigate the incidence of AKI in patients with LA-SCCHN during and after treatment with high-dose cisplatin-based CRT, to identify risk factors for cisplatin-induced AKI, and to describe the impact of AKI on long-term renal function and treatment outcomes. Methods: This is a retrospective cohort study with measurements of renal function before CRT, weekly during CRT, every 1 or 2 days during hospitalizations, and 3 and 12 months after CRT in patients with LA-SCCHN. AKI was defined as increase in serum creatinine (sCr) of ≥1.5 times baseline or by ≥0.3 mg/dL (≥26.5 μmol/L) using the Kidney Disease Improving Global Outcomes (KDIGO) classification. Logistic regression models were estimated to analyze renal function over time and to identify predictors for AKI. Results: One hundred twenty-four patients completed all measurements. AKI was reported in 85 patients (69%) with 112 episodes of AKI. Sixty of 85 patients experienced 1 AKI episode; 20 patients experienced ≥2 AKI episodes. Ninety-three (83%) AKI episodes were stage 1, 13 (12%) were stage 2, and 6 (5%) AKI episodes were stage 3. Median follow-up time was 29 months (Interquartile Range, IQR 22-33). Hypertension (Odds Ratio, OR 2.7, 95% Confidence Interval, CI 1.1-6.6; p = 0.03), and chemotherapy-induced nausea and vomiting (CINV; OR 4.3, 95% CI 1.6-11.3; p = 0.003) were associated with AKI. In patients with AKI, renal function was significantly more impaired at 3 and 12 months post-treatment compared to patients without AKI. AKI did not have a negative impact on treatment outcomes. Conclusion: AKI occurred in 69% of patients with LA-SCCHN undergoing CRT with high-dose cisplatin. Long-term renal function was significantly more impaired in patients with AKI. Hypertension and CINV are significant risk factors. Optimizing prevention strategies for CINV are urgently needed

In vivo tissue cholesterol efflux is reduced in carriers of a mutation in APOA1

<p>Atheroprotection by high density lipoprotein (HDL) is considered to be mediated through reverse cholesterol transport (RCT) from peripheral tissues. We investigated in vivo cholesterol fluxes through the RCT pathway in patients with low plasma high density lipoprotein cholesterol (HDL-c) due to mutations in APOA1. Seven carriers of the L202P mutation in APOA1 (mean HDL-c: 20 +/- 19 mg/dl) and seven unaffected controls (mean HDL-c: 54 +/- 11 mg/dl, P <0.0001) received a 20 h infusion of C-13(2)-cholesterol (C-13-C). Enrichment of plasma and erythrocyte free cholesterol and plasma cholesterol esters was measured. With a three-compartment SAAM-II model, tissue cholesterol efflux (TCE) was calculated. TCE was reduced by 19% in carriers (4.6 +/- 0.8 mg/kg/h versus 5.7 +/- 0.7 mg/kg/h in controls, P = 0.02). Fecal C-13 recovery and sterol excretion 7 days postinfusion did not differ significantly between carriers and controls: 21.3 +/- 20% versus 13.3 +/- 6.3% (P = 0.33), and 2,015 +/- 1,431 mg/day versus 1456 +/- 404 mg/day (P = 0.43), respectively. TCE is reduced in carriers of mutations in APOA1, suggesting that HDL contributes to efflux of tissue cholesterol in humans. The residual TCE and unaffected fecal sterol excretion in our severely affected carriers suggest, however, that non-HDL pathways contribute to RCT significantly.</p>

Genetic Variation at the Phospholipid Transfer Protein Locus Affects Its Activity and High-Density Lipoprotein Size and Is a Novel Marker of Cardiovascular Disease Susceptibility

Background-In contrast to clear associations between variants in genes participating in low-density lipoprotein metabolism and cardiovascular disease risk, such associations for high-density lipoprotein (HDL)-related genes are not well supported by recent large studies. We aimed to determine whether genetic variants at the locus encoding phospholipid transfer protein (PLTP), a protein involved in HDL remodeling, underlie altered PLTP activity, HDL particle concentration and size, and cardiovascular disease risk. Methods and Results-We assessed associations between 6 PLTP tagging single nucleotide polymorphisms and PLTP activity in 2 studies (combined n = 384) and identified 2 variants that show reproducible associations with altered plasma PLTP activity. A gene score based on these variants is associated with lower hepatic PLTP transcription (P = 3.2 x 10(-18)) in a third study (n = 957) and with an increased number of HDL particles of smaller size (P = 3.4 x 10(-17)) in a fourth study (n = 3375). In a combination of 5 cardiovascular disease case-control studies (n = 4658 cases and 11 459 controls), a higher gene score was associated with a lower cardiovascular disease risk (per-allele odds ratio, 0.94; 95% confidence interval, 0.90 to 0.98; P = 1.2 x 10(-3); odds ratio for highest versus lowest gene score, 0.69; 95% confidence interval, 0.55 to 0.86; P = 1.0 x 10(-3)). Conclusions-A gene score based on 2 PLTP single nucleotide polymorphisms is associated with lower PLTP transcription and activity, an increased number of HDL particles, smaller HDL size, and decreased risk of cardiovascular disease. These findings indicate that PLTP is a proatherogenic entity and suggest that modulation of specific elements of HDL metabolism may offer cardiovascular benefit. (Circulation. 2010; 122: 470-477.