Eicosapentaenoic acid inhibits intestinal ß-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.

The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal ß-carotene absorption. ß-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered ß-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of ß-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of ß-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal ß-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal ß-carotene absorption.

Platelet indices as prognostic markers of ischemic stroke and their correlation with lipid profile.

OBJECTIVE: Stroke is the cause of one in eight deaths and adds a dreadful burden of disability for the patients. Ischemic stroke is caused by a loss of blood supply to brain due to sudden occlusion of the arterial system, caused by an emboli or thrombus. Our aim was to correlate platelet indices, total cholesterol ratio, and various comorbidities with stroke. METHODS: A cross-sectional study was performed from 2020-2022 with 132 stroke patients admitted to the SRM Medical College Hospital and Research Center, India. Detailed clinical examination was performed. Venous blood samples were drawn at the time of admission to estimate platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and platelet crit (PCT). Overnight fasting serum samples were obtained for lipid profiling. RESULTS: Among the participants in our study, maximum belonged to the age group 50 to 59 years (34.1%) and majority were males (79.5%). In terms of comorbidities, 85.6% of the participants had diabetes, 42.4% had hypertension and 22% had dyslipaedemia. All platelet and lipid parameters were found to be similar between patients with and without comorbidities. While all platelet indices increased with the increase in severity of stroke, we found that PDW is most reliable in predicting stroke with an area under the receiver operator curve of 0.942, with a sensitivity and specificity of 92.1% at cut-off value 14. All platelet parameters also significantly increased in patients with severe lipid dysfuction, establishing a correlation between lipid profile, platelet indices and stroke. CONCULSION: We found a significant relationship between all platelet parameters and stroke. Thus, we believe that patients with risk factors for atherosclerosis should have their platelet indices assessed periodically before the development of cerebrovascular events. Furthermore, dyslipidemia if properly treated, is a modifiable risk factor for stroke, which can decrease morbidity and mortality leading to a healthier society.

Prevalence of ocular signs and subclinical vitamin A deficiency and its determinants among rural pre-school children in India.

OBJECTIVE: To assess the magnitude and determinants of vitamin A deficiency (VAD) and coverage of vitamin A supplementation (VAS) among pre-school children. DESIGN: A community-based cross-sectional study was carried out by adopting a multistage, stratified, random sampling procedure. SETTING: Rural areas of eight states in India. SUBJECTS: Pre-school children and their mothers were covered. RESULTS: A total of 71,591 pre-school children were clinically examined for ocular signs of VAD. Serum retinol concentrations in dried blood spots were assessed in a sub-sample of 3954 children using HPLC. The prevalence of Bitot spots was 0·8%. The total ocular signs were significantly higher (P < 0·001) among boys (2·6%) compared with girls (1·9%) and in older children (3-4 years) compared (P < 0·001) with younger (1-2 years), and were also high in children of labourers, scheduled castes and illiterate mothers. The odds of having Bitot spots was highest in children of scheduled caste (OR = 3·8; 95% CI 2·9, 5·0), labourers (OR = 2·9; 95% CI 2·1, 3·9), illiterate mothers (OR = 2·7; 95% CI 2·2, 2·3) and households without a sanitary latrine (OR = 5·9; 95% CI 4·0, 8·7). Subclinical VAD (serum retinol level <20 µg/dl) was observed in 62% of children. This was also relatively high among scheduled caste and scheduled tribe children. The rate of coverage of VAS was 58%. CONCLUSIONS: The study revealed that VAD is a major nutritional problem and coverage of VAS was poor. The important determinants of VAD were illiteracy, low socio-economic status, occupation and poor sanitation. Strengthening the existing VAS programme and focused attention on dietary diversification are essential for prevention of VAD.

Successful living donor liver transplantation in portomesenteric thrombosis.

Chronic portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to the risks involved and higher morbidity. In this report, we describe a surgical strategy for living donor liver transplant in patient with complete PVT using venovenous bypass from the inferior mesenteric vein (IMV) and then using a jump graft from the IMV for portal inflow into the graft. IMV is a potential source for portal inflow in orthotopic liver transplant.

Binding and stabilization of transthyretin by curcumin.

Biophysical evidences suggest that transthyretin (TTR) tetramer dissociation to the monomeric intermediate and subsequent polymerization leads to amyloid fibril formation, which is implicated in the pathogenesis of familial amyloid polyneuropathy (FAP) and senile systemic amyloidosis (SSA). Hence, inhibition of fibril formation is considered a potential therapeutic strategy. Here in we demonstrate that curcumin, a phenolic constituent of curry spice turmeric, binds to the active site of TTR through fluorescence quenching and ANS displacement studies. Binding of curcumin appears to inhibit the denaturant induced tertiary and quaternary structural changes in TTR as monitored by intrinsic emission fluorescence and glutaraldehyde cross-linking studies. However, curcumin did not bind to TTR at acidic pH. Protonation/ isomerization of the side chain oxygen atoms of curcumin at low pH might hamper the binding. These results suggest that curcumin binds to and stabilizes TTR thereby highlight the importance of the side chain conformations of the ligand in binding to TTR.

Screening for distress (the sixth vital sign) in a global recession: sustainable approach to maintain patient-centered care.

A substantial volume of research on the psychosocial impact of cancer clearly indicates that patients are likely to experience emotional distress. There is also evidence that psychosocial interventions aimed at decreasing distress provide tangible cost offsets to cancer patients, caregivers and treating institutions. One seemingly major drawback in the setup and delivery of a fully fledged screening program for distress is the extensive pecuniary requirements. Given that the categorical need for distress screening may be confounded by financial limitations, especially in a time of global recession, a cost-effective alternative seems appropriate. The model proposed herein is not a substitute screening program, nor does it eliminate the need to allocate resources to address the identified risks. It does, however, offer a cost-effective alternative to implement a high-risk distress patient identifying process, quite similar to algorithms used in screening for prostate cancer.

A systematic review of interventions and outcomes in lung cancer metastases to the spine.

Seventy percent of cancer patients will have metastatic bone disease, most commonly in the vertebra. Prognosis of metastatic lung cancer is poor and treatment is mostly palliative. To-date, there is no systematic review on the ideal treatment for lung cancer with spinal metastases in regards to mortality. Literature searches were performed based on PRISMA guidelines for systematic review. Thirty-nine studies comprising 1925 patients treated for spinal metastases of lung cancer met inclusion criteria. All analyses were performed using SAS and SPSS. Data were analyzed for meaningful comparisons of baseline patient characteristics, primary cancer type, metastatic lesion characteristics, treatment modality, and clinical and radiologic outcomes. Significantly greater mean survival length was seen in the non-surgical group (8.5 months, SD 6.6, SEM 0.17) compared to the surgical group (7.5 months, SD 4.5, SEM 0.25; p = 0.013). There was no statistically significant survival difference between different types of primary lung cancer: NSCLC (8.3 months, SD 13.8, SEM 0.91) and SCLC (7.0 months, SD 4.6, SEM 0.46; p = 0.36). Number of vertebral levels involved per lesion also did not exhibit significant difference: single lesion (11.3 months, SD 6.8, SEM 2.2) and multiple lesions (13.8 months, SD 15.7, SEM 3.6; p = 0.64). For patients with symptomatic spinal metastases from lung cancer, non-operative approaches experience significantly better survival outcomes (p = 0.013). Future clinical studies are needed to determine the best treatment algorithm to help maximize outcomes and minimize mortality in metastatic lung cancer.

Left Inferior Vena Cava from the Perspective of Laparoscopic Donor Surgeon: Anatomic Considerations and Surgical Implications.

Renal vascular aberrations are not uncommon cause for rejection of living kidney donors. While screening a donor for laparoscopic nephrectomy, we encountered a rare, yet important aberration in the form of left-sided inferior vena cava (IVC). There was an initial dilemma regarding the acceptability of the donor and which side kidney to select for donation. Scant literature is available on this particular clinical scenario, and only after a detailed study of the embryology and anatomy of IVC, were we able to make an informed choice. This article highlights the surgical anatomy and clinical implications of this rare condition from the perspective of laparoscopic donor surgeon.

The selective use of magnetic resonance cholangiopancreatography in the imaging of the axial biliary tree in patients with acute gallstone pancreatitis.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an emerging modality in the management of acute gallstone pancreatitis (AGP). The aim of this study was to assess the impact following the introduction of MRCP in the management of AGP in a tertiary referral unit. METHODS: Patients presenting with AGP from January 2002 to December 2004 were reviewed to assess the impact of the introduction of MRCP in June 2003. The indication for MRCP was suspected common bile duct (CBD) stones in the absence of biliary sepsis. Definitive treatment for AGP was laparoscopic cholecystectomy, with endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy reserved for patients unfit for cholecystectomy and those with biliary sepsis. RESULTS: 249 patients were identified of whom 36 (14.5%) underwent ERCP and sphincterotomy as definitive treatment. 96 patients with a non-dilated CBD and normal or resolving liver function tests proceeded to laparosocopic cholecystectomy and intraoperative cholangiogram (IOC), 8 (8.5%) of whom had CBD stones intraoperatively. Eleven patients underwent cholecystectomy during pancreatic necrosectomy. Of those undergoing preoperative diagnostic biliary tract imaging, ERCP was undertaken in 57 patients and MRCP in 49 patients. There was no significant difference in serum bilirubin levels [ERCP 43 mmol/l (18-204) vs. MRCP 39 mmol/l (24-180), p = NS] or the proportion of patients with CBD stones [ERCP 10 (17.5%) vs. MRCP 7 (14.2%), p = NS] between the two groups. Patients who underwent MRCP had a shorter median hospital stay [MRCP 5 days (range: 3-14) vs. ERCP 9 days (range: 4-20), p < 0.01] and higher rate of cholecystectomy during the index admission (MRCP 83.3% vs. ERCP 67.2%, p < 0.05). There was a high degree of correlation between preoperative MRCP results and findings of subsequent IOC or therapeutic ERCP (area under ROC curve: 0.94). CONCLUSIONS: MRCP is an accurate modality for imaging the axial biliary tree in patients with AGP. Selective use of MRCP reduces the need for ERCP and results in shorter hospital stay. and IAP.

Family of developmentally regulated, maternally expressed Drosophila RNA species detected by a v-myc probe.

Drosophila melanogaster genomic sequences that hybridize with v-myc have been reported (B.-Z. Shilo and R. A. Weinberg, Proc. Natl. Acad. Sci. U.S.A. 78:6789-6792, 1981). We have detected Drosophila RNA sequences that also hybridize with v-myc. In an attempt to characterize these RNA sequences, we used v-myc hybridization probes to isolate Drosophila genomic segments. None of the Drosophila genomic or cDNA clones that we have isolated hybridize with the 3' exon of v-myc. Preliminary nucleotide sequence analyses have revealed sufficient homology to account for the observed hybridization between v-myc and the Drosophila clones but have failed to detect significant amino acid sequence homology. Thus is seems unlikely that the mRNA sequences or the genomic sequences that we have isolated by hybridization with v-myc represent homologs of the vertebrate myc gene. Despite the lack of structural homology between the cloned Drosophila sequences and v-myc, we have investigated the pattern of expression of those RNA species that hybridize with v-myc. Polyadenylic acid-containing transcripts of 2.7, 2.2, and 1.7 kilobases (kb) in embryos, pupae, adults, and Kc cells and an additional 1.4-kb transcript in adults were complementary to the Drosophila genomic clones and to v-myc. The 1.7- and 2.2-kb transcripts were localized on polyribosomes in Kc cells. The 1.7- and 2.2-kb transcripts were present after 45 min, 2 h, and 4 h of embryonic development, but by 16 h of development their levels had decreased by more than sixfold. During metamorphosis, two peaks of expression of the 1.7- and 2.2-kb transcripts were observed, at 6 and 72 h postpupariation. The 1.4-kb RNA species was first detected at 72 h postpupariation. In adults, the 1.7- and 2.2-kb transcripts were detected only in ovaries in females, whereas the 1.4-kb transcript was present in female nonovarian RNA and in males. These results suggest that the transcripts in early embryos are of maternal origin.

Palliation for suspected unresectable hilar cholangiocarcinoma.

AIM: The aim of this study was to evaluate the outcome of different techniques of palliation for patients with hilar cholangiocarcinoma. METHOD: All patients treated with palliative intent between 1988 and 2004 at the Royal Infirmary of Edinburgh were reviewed. Patients were analysed on an intention to treat basis. Demographics, procedure and outcome (including re-admissions) were recorded. RESULTS: Two hundred and thirty-three patients underwent palliative treatment for suspected hilar cholangiocarcinoma. The diagnosis was confirmed histologically in 109 patients. The procedure related morbidity and mortality was 54/225 and 18/207 respectively. Seventy-one patients required re-admission. Twenty patients underwent surgical biliary bypass for jaundice. Those undergoing surgical palliation had a longer median (95% CI) time to re-admission (16 (0-36) vs.7 (2-12) weeks, p=0.001). Endoscopic retrograde cholangio-pancreatography (ERCP) and stenting was only successful in 28 patients and was associated with a significantly higher re-admission rate compared to patients in whom ERCP was not performed (60/179 vs. 4/27, p=0.050). The overall median (95% CI) survival was 145 (124-185) days. CONCLUSION: Current options for palliation of hilar cholangiocarcinoma provide good short term success but are all associated with significant early and late morbidity. Due to its low success and association with an increased re-admission rate, ERCP for definitive palliation should not be used in the first line staging and management of these patients.

Predicting survival in patients with hepatocellular carcinoma: a UK perspective.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a cancer of rising incidence in the UK. The aim of this study was to compare the Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC) classifications as predictors of survival in UK patients with HCC. METHODS: Data were analysed from a prospective database maintained in a specialist hepatobiliary unit from 1998 to 2003. Each system was assessed for its discriminatory power, monotonicity of gradient, and independent contribution to prediction of mortality status based on a multivariate model. RESULTS: One hundred and two patients (77 males, 25 females) were identified with a median age of 65 (range, 14-87) years. The overall median survival time was 13 months and the one- and five-year survival rates were 52.9% (95% CI: 43.2%, 62.6%) and 35.3% (95% CI: 26.0%, 44.6%), respectively. All three classification systems had the capacity to differentiate between patient survival times across different stages. The Okuda system was superior in overall discriminatory power and in strength of monotonicity. The BCLC system, however, made the highest independent contribution of all three systems in predicting survival in the Cox regression model. CONCLUSIONS: All three classification systems were effective in predicting survival for patients with HCC in a UK population.

Follow-up and outcomes for resection of colorectal liver metastases in Edinburgh.

AIM: The aim of this study was to assess the value of a defined follow-up protocol for patients undergoing potentially curative hepatic resection for colorectal hepatic metastases. METHODS: A standard protocol for the duration of the study consisted of clinical assessment, serum carcinoembryonic antigen (CEA) and computed tomography. Patterns of recurrence, method and timing of diagnosis and outcome were recorded. RESULTS: One hundred and ninety-one patients underwent potentially curative resection from 1989 to 2004 of whom 103 developed recurrence. The median (inter-quartile range) follow-up was 24.4 (6.5-42.3) months. The median (IQR) time to recurrence and overall survival was 25.0 (10 -not yet reached) and 45.2 (21-123) months, respectively. Seventeen patients (8.9%) underwent further surgery with curative intent. Fifty-five patients (57.9%) had recurrence diagnosed at routine follow-up with 71% (44/62) being diagnosed by CEA and CT. The CEA was elevated in 85.7% (72/84 patients) at the time of diagnosis of recurrence. CONCLUSION: Although the detection of recurrent disease is common during follow-up after hepatic resection for colorectal metastases, few patients will be suitable for further intervention with curative intent. The exact nature of the follow-up protocol remains to be determined but if it is going to be performed it should be most intensive within the first 3 years.

Sustainable leprosy related disability care within integrated general health services: findings from Salem District, India.

The main focus of leprosy control has been case detection and treatment delivery with relative neglect of prevention of disability. Absence of reliable data and lack of research have added to the problem. This raised concerns about the capacity of the general health system to address the needs of people living with leprosy-related disabilities. In this prospective study appropriate services for people living with leprosy-related disabilities were introduced in the form of self-care training, guidance and monitoring by the general health staff facilitated by a non-governmental organisation leprosy centre in a district in south India with a population of 3.1 million (estimated in 2005). The staff identified 1232 people with leprosy-related disabilities and trained them in self-care. Follow-up assessments indicated that 86% were found to be practising self-care regularly and all the 239 general health workers were found to be actively involved. The most heartening outcome was the healing of plantar ulcers in 70% of people at the 1-year follow up. This intervention is sustainable because of the simplicity of the procedures and the involvement of all health staff including supervisors.

Predictors of Non-adherence to Immunosuppressive Therapy in Asian Liver Transplant Recipients.

BACKGROUND: Adherence to immunosuppressive medications has been shown to affect post-transplant outcomes. We aimed to determine the level of adherence to immunosuppressive therapy in liver transplant (LT) recipients and to elucidate factors associated with it, as well as patient preferences on the dosing schedule. METHODS: LT recipients were recruited during transplant clinic follow-up. A validated Morisky 8-item questionnaire was completed by patients to assess their adherence to immunosuppressive therapy. Adherence was determined by the sum of the responses to the questionnaire. Low, medium, and high adherence were defined by a Morisky score of >2, 1 to 2, and 0, respectively. Data on the patient's socio-economic and clinical background, dosing schedule of immunosuppressant medications, and patient preferences were included in the questionnaire. RESULTS: A total of 107 LT recipients were approached and 75 completed the questionnaire. The majority of patients (48/74, 64.9%) preferred a once-daily medication regimen. The proportion of high adherence was 24/75 (32.0%), medium adherence was 51/75 (42.7%), and low adherence was 19/75 (25.3%). Multivariate analysis showed younger age and post-transplant duration >5 years as independent predictors for low adherence. Among low-adherence patients, 16/19 (84.2%) patients were on a twice-daily regimen, and, of these, 14/16 (87.5%) preferred their medications to be reduced to once daily. CONCLUSIONS: A significant proportion (68%) of LT recipients had low to moderate adherence to medications, with younger age and longer post-transplant duration of >5 years as independent predictors. Early identification of at-risk patients is essential to allow implementation of measures to improve adherence. Simplifying medication regimens to once daily is a potential way to improve adherence.

Role of Coronary Angiography in Pre-Liver Transplantation Cardiac Evaluation: Experience From an Asian Transplant Institution.

BACKGROUND: Liver transplant (LT) patients with significant coronary artery disease (CAD) have poorer outcomes. Pre-LT coronary angiography (CA) is associated with significant complications in cirrhotic patients. METHODS: This study aimed to identify predictors of abnormal CA in pre-LT cardiac assessment and to develop a predictive model to reduce unnecessary CA. From January 2006 to June 2013, 122 patients underwent CA based on the current institutional protocol. RESULTS: Forty-one (33.6%) patients had abnormal CA. Univariate analysis showed age ≥65 years (P = .001), cryptogenic cirrhosis (P = .046), cardiac comorbidities (P = .027), ischemic heart disease (IHD; P = .002), left ventricular hypertrophy (LVH; P = .004), hypertension (P = .002), diabetes mellitus (P = .017), dyslipidemia (P < .001), metabolic syndrome (P = .003), ≥2 CAD risk factors (P = .001), and high Framingham risk score (hard CAD risk, P = .018; cardiovascular disease: lipids, P = .002; body mass index, P < .001) to be significant predictors of abnormal CA. A predictive model was developed with the use of multivariable logistic regression and included diabetes, dyslipidemia, IHD, age ≥65 years, and LVH, achieving a specificity of 55.1% and sensitivity of 90.0%. This would reduce unnecessary CA by up to one-half in our study population (from 81 to 35) while maintaining a false negative rate of only 8.5%. CONCLUSIONS: Diabetes, dyslipidemia, IHD, age ≥65 years, and LVH appear to be predictors of abnormal CA in pre-LT patients. Our predictive model may help to better select patients for CA, although further validation is required.

Food-Based Interventions to Modify Diet Quality and Diversity to Address Multiple Micronutrient Deficiency.

Global data indicate a high prevalence of hidden hunger among population. Deficiencies of certain micronutrients such as folic acid, iodine, iron, and vitamin A have long lasting effects on growth and development and therefore have been a National priority from many decades. The strategy implemented so far limits to the use of supplemental sources or fortified foods in alleviating the burden of deficiencies. These approaches however undermine the food-based strategies involving dietary diversification as the long-term sustainable strategy. There is lack of understanding on the level of evidence needed to implement such strategies and the level of monitoring required for impact evaluation. Dietary diversity concerns how to ensure access for each individual to a quality and safe diet with adequate macro- and micronutrients. The key to success in using dietary diversity as a strategy to tackle hidden hunger is in integrating it with the principles of bioavailability, translated to efficient food synergies with due emphasis on food accessibility, affordability, and outdoor physical activity/life style modifications. Promoting enabling environment and sustainable agriculture is crucial for practicing dietary diversification with behavior change communication as an integral segment. It can be concluded that food-based strategies require careful understanding of the factors associated with it and moderate it to form an effective strategy for controlling multiple micronutrient deficiencies.

The extent of resection influences outcome following hepatectomy for colorectal liver metastases.

BACKGROUND: The acceptable indications for liver resection in patients with colorectal metastases have increased significantly in the last decade. It is thus becoming more difficult to ascertain the limitations for selection as the boundaries have been greatly extended. This has resulted in not only more extensive resections, but more atypical and bilobar resections. The aim of this study was to compare the outcome of patients undergoing different extent of liver resection in a specialist unit. METHODS: All patients undergoing liver resection for colorectal metastases at the Royal Infirmary of Edinburgh between October 1988 and April 2001 were reviewed. Patients were allocated into one of three groups: standard group, extended group, and segmental group. Patient information was collected from a prospectively completed database. RESULTS: One hundred and thirty-seven patients had liver resections for colorectal metastases during the study period. There were 69 standard hepatectomies, 41 extended resections and 27 segmental resections. CEA level was significantly lower in the segmental group(p = 0.012). There was a significant difference between the groups in terms of median operating time (p < 0.0001, Kruskal-Wallis test), operative blood loss (p = 0.006, Kruskal-Wallis test) and post-operative stay ( p = 0.036, Kruskal-Wallis test). Major post-operative complications were similar between standard and extended resections but less following segmental resection (p = 0.050. Predicted median survival was 51 months following standard resection, 23 months following extended resection and 59 months after segmental resection ( p = 0.037, log rank test), however, there was no difference between the three groups for actual 5-year survival (p = 0.662, Pearson chi-square test). CONCLUSION: Morbidity and mortality rates were comparable with other previous studies as was overall survival, although survival in patients undergoing extended resections was reduced. There was an acceptable level of morbidity and mortality for all three groups. Patients undergoing segmental resection had fewer complications, shorter length of stay, and the longest median survival suggesting adequate oncological clearance. Segmental resection has a role for favourably placed tumour deposits if oncological clearance can be ensured. Extended liver resections have a role for selected patients with bilobar colorectal metastases or large solitary deposits close to the hepatic vein confluence.