Lipid Profile and Ultrasonographic Grading in Alcoholic and Non Alcoholic Fatty Liver Patients.

Background Fatty liver disease (FLD) is a common and major chronic liver disease. It has been implicated that patients have disorders of lipid metabolism and are involved in the pathogenesis of fatty liver. Hence, it was designed to observe the association between lipid profile and fatty liver disease. Objective This study was undertaken to evaluate the association of lipid profile status, hemoglobin and albumin levels with fatty liver disease patients diagnosed based on ultrasonography (USG). Method This Cross-sectional study was undertaken in the Department of Internal Medicine with the collaboration of the Department of Radiology and Department of Biochemistry, Universal College of Medical Sciences-Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from March 2019 to February 2020 in a total of 100 patients diagnosed with fatty liver disease by ultrasonography. The fasting blood was collected for lipid profile and carried out in the automated analyzer following standard protocol. Result In 100 cases, the male to female ratio was 1.8:1. Fifty six percent of the total cases presented with alcoholic fatty liver disease (AFLD) while the remaining 44% with nonalcoholic fatty liver disease (NAFLD). The spectrum of lipid abnormality was observed with increased total cholesterol (TC), Low Density Lipoprotein (LDL), increased triglycerides (TG), Very Low Density Lipoprotein (VLDL) in alcoholic fatty liver disease cases as compared to nonalcoholic fatty liver disease cases. However, it has been observed that TG/HDL and Non-HDL/HDL were higher in nonalcoholic fatty liver disease as compared to alcoholic fatty liver disease. Moreover, a statistically significant difference was observed in HDL between AFLG2 and NAFLG2 (p-value: 0.012). Conclusion Dyslipidemia and decreased HDL have been implicated in fatty liver diseases. USG in conjunction with Non-HDL/HDL, TG/HDL, hemoglobin, and albumin can be useful in early screening and monitoring of dyslipidemia in fatty liver patients.

Diagnostic Accuracy of Intraoperative Frozen Section in Ovarian Neoplasms: Experience in a Tertiary Oncology Centre.

Background Ovarian cancer is the second most common type of female genital tract malignancy. Treatment planning differs for benign, borderline and malignant subtypes of surface epithelial tumours and depends on accurate histopathological diagnosis. A pre-operative diagnosis of the nature of ovarian tumors is not always reliable. Frozen section is a valuable diagnostic tool in rapid intraoperative categorization of ovarian masses and thereby helps in planning the surgical management. Adequate management and treatment of ovarian carcinoma requires a complete surgical staging supported by frozen-section examination. To achieve this goal it is necessary to have a high level of accuracy. Objective To assess the accuracy of intra-operative frozen section in the diagnosis of various categories of ovarian neoplasm conducted in Rajiv Gandhi Cancer Institute and Research Centre. Method Intra-operative frozen sections for suspected ovarian neoplasm that underwent surgery as primary line of therapy at this institution were analyzed retrospectively from Jan. 2014 - Dec. 2015. The results of frozen section were compared with the final histopathology diagnosis on paraffin sections and the overall accuracy, sensitivity, specificity, positive and negative predictive values were determined. Result The study included 159 cases and the mean age of patients was 44.72±14.28 years (Range 19-75 years). The mean size of tumor was 12.5±5.9 cm. Sensitivity of frozen section for benign, borderline and malignant tumors was 98.53%, 73.33% and 94.74% respectively and the related specificities were 95.60%, 96.53% and 100% respectively. There were 150 concordant cases and 9 discordant cases. Overall diagnostic accuracy of frozen section was 94.33%. Conclusion Intra-operative frozen section diagnosis appeared to be an accurate and comparable technique for the histopathology diagnosis of ovarian tumors.

A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients. PATIENTS AND METHODS: In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. Placebo patients with progressive disease (PD) could cross over to 10-mg/kg intetumumab alone or with docetaxel. The primary end-point was progression-free survival (PFS). The secondary end-points included tumor response (complete response + partial response, CR + PR), prostate-specific antigen (PSA) response, and overall survival (OS). RESULTS: All efficacy end-points favored placebo over intetumumab, including PFS (median 11.0 versus 7.6 months, P = 0.014), tumor response (20% versus 16%, P = 0.795), PSA response (68% versus 47%, P = 0.018), OS (median 20.6 versus 17.2 months, P = 0.163). Common all-grade adverse events (AEs) with placebo and intetumumab were alopecia (43% versus 26%); diarrhea, leukopenia (both 34% versus 27%); neutropenia (35% versus 23%). Grade ≥ 3 leukopenia (28% versus 17%) and neutropenia (26% versus 18%) occurred more often with placebo than with intetumumab. Intetumumab serum concentrations increased with repeated dosing and did not reach steady-state. Greater decreases in N-telopeptide of type I collagen (NTx), C-telopeptide (CTx) and CTCs occurred with intetumumab than with placebo. CONCLUSION: The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.

Isolated lymph node recurrence in epithelial ovarian cancer - management and outcome.

INTRODUCTION: The aim of our study was to assess the clinical outcome of isolated lymph node recurrence in patients with epithelial ovarian cancer treated by surgery and to analyze the impact of various clinico-pathological factors on prognosis. MATERIAL AND METHODS: We conducted a retrospective analysis of all the epithelial ovarian cancer patients who underwent secondary lymphadenectomy surgery for isolated lymph node recurrence at our institute from 2013 to 2020. Univariate analysis of various factors influencing the post-recurrence disease free survival and post-recurrence survival was done using Kaplan-Meier for categorical variables and cox-proportional hazard progression for continuous variables. RESULTS: A total of 21 patients of isolated lymph node recurrence were treated surgically during the study period. The median disease free interval to develop lymph nodal recurrence was 13 months. All the patients achieved complete resection to no gross residual disease without any significant morbidity associated with the procedure. The median post-recurrence disease free survival after treatment of lymph node recurrence was 25 months with 3-year post-recurrence survival of 72% and 3-year overall survival of 85%. Amongst the factors influencing post-recurrence disease free survival, young age (< 50 years), para-aortic lymph node dissection at initial surgery and single site of lymph node recurrence were significantly associated with better prognosis. A single site of lymph node recurrence was associated with significantly better post-recurrence survival. CONCLUSIONS: Complete resection is feasible for epithelial ovarian cancer patients presenting with isolated lymph node recurrence, without any significant perioperative morbidity. When combined with postoperative adjuvant chemotherapy, complete resection is associated with favourable survival outcomes. Young age, para-aortic lymph node dissection during primary surgery and single site of lymph node recurrence are associated with better prognosis.

Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor ß.

BACKGROUND AND OBJECTIVE: Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix-degrading activities. MATERIAL AND METHODS: Fibroblasts were incubated with CBD in serum-free medium for 1-6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor ß and the extracellular matrix molecule fibronectin were measured by ELISA. Pro-MMP-1 and total MMP-2 were measured by ELISA. Activity of MMP-2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP-2. Data were analysed using ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor ß production by as much as 40% (p < 0.001), while higher concentrations decreased it by as much as 40% (p < 0.0001). Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP-2 activity (p < 0.02). CONCLUSION: The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor ß and fibronectin, while decreasing MMP production and activity.

Statins regulate interleukin-1ß-induced RANKL and osteoprotegerin production by human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Three-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase competitive inhibitors, or 'statins', are widely used for lowering cholesterol and thereby reducing the risk of a heart attack. Recent data suggest that statins influence metabolic bone activity by their actions on three molecules: RANKL; RANK; and osteoprotegerin (OPG), the soluble decoy receptor for RANKL. The purpose of this study was to evaluate OPG and RANKL production in resting and interleukin-1ß (IL-1ß)-activated human gingival fibroblasts (HGFs), and to determine the effect of statins on their production. MATERIAL AND METHODS: Fibroblasts were pre-incubated with atorvastatin or simvastatin for 24h in serum-free medium, and then incubated with IL-1ß for 6d. The concentration of OPG or RANKL in culture supernatants was measured by specific ELISA. Data were analyzed using analysis of variance and Scheffe's F procedure for post hoc comparison. RESULTS: IL-1ß (1×10(-8) m) stimulated a significant increase in the production of OPG on days 1, 3 and 6. There was a trend towards an increase in RANKL production as a result of stimulation with IL-1ß. Both statins, at multiple concentrations, significantly increased the constitutive RANKL/OPG ratio. Only atorvastatin at the highest concentration (5×10(-6) m) significantly increased the IL-1ß-stimulated RANKL/OPG ratio. CONCLUSION: IL-1ß significantly increased OPG production by HGFs. The statins differed minimally in their effects on OPG and RANKL production by resting and IL-1ß-activated HGFs. Both statins increased constitutive RANKL/OPG ratios, but generally not IL-1ß-stimulated ratios. Thus, statins may influence the production of RANKL and OPG by HGFs to favor bone catabolism, under noninflammatory conditions.

Down-regulation of Leucaena leucocephala cinnamoyl CoA reductase (LlCCR) gene induces significant changes in phenotype, soluble phenolic pools and lignin in transgenic tobacco.

cDNA and genomic clones of cinnamoyl CoA reductase measuring 1011 and 2992 bp were isolated from a leguminous pulpwood tree Leucaena leucocephala, named as LlCCR. The cDNA exhibited 80-85% homology both at the nucleotide and amino acid levels with other known sequences. The genomic sequence contained five exons and four introns. Sense and antisense constructs of LlCCR were introduced in tobacco plants to up and down-regulate this key enzyme of lignification. The primary transformants showed a good correlation between CCR transcript levels and its activity. Most of the CCR down-regulated lines displayed stunted growth and development, wrinkled leaves and delayed senescence. These lines accumulated unusual phenolics like ferulic and sinapic acids in cell wall. Histochemical staining suggested reduction in aldehyde units and increased syringyl over guaiacyl (S/G) ratio of lignin. Anatomical studies showed thin walled, elongated xylem fibres, collapsed vessels with drastic reduction of secondary xylem. The transmission electron microscopic studies revealed modification of ultrastructure and topochemical distribution of wall polysaccharides and lignin in the xylem fibres. CCR down-regulated lines showed increased thickness of secondary wall layers and poor lignification of S2 and S3 wall layers. The severely down-regulated line AS17 exhibited 24.7% reduction of Klason lignin with an increase of 15% holocellulose content. Contrarily, the CCR up-regulated lines exhibited robust growth, development and significant increase in lignin content. The altered lignin profiles observed in transgenic tobacco lines support a role for CCR down-regulation in improving wood properties of L. leucocephala exclusively used in the pulp and paper industry of India.

Iatrogenic acid-induced gingival recession during crown cementation: A case report.

Accidental contact of various chemicals in dentistry may cause damage to the gingiva. A male patient presented for a full mouth rehabilitation with ceramic crowns. The patient underwent the steps of ceramic crown preparation uneventfully. At the time of crown delivery, cotton rolls were placed in several vestibular areas for isolation. They were regularly changed during different steps of etching and cementation process, which included the use of Multilink Primer B (Ivoclar Vivadent™). On removal of the cotton roll in the area of upper right canine, the gingival tissues appeared blanched and grayish white. The cotton roll was found to have absorbed some etching material in it. As the patient was asymptomatic, he was dismissed. Two weeks later, the patient presented with inflammation and gingival recession in the same area. Initially, he was treated palliatively, and subsequently, he received a connective tissue graft on the upper right canine. This case report showed that acid etching material used during the prosthodontic cementation may have caused a gingival recession, which was successfully treated with tunnel flap and connective tissue graft. Optimal isolation of the operative field should be performed to avoid this problem.

Detection of meticillin-resistant staphylococcus aureus (MRSA) colonization in newborn infants using real-time polymerase chain reaction (PCR).

OBJECTIVE: Meticillin-resistant staphylococcus aureus (MRSA) colonization on neonatal units is a common and important clinical problem. Effectiveness of polymerase chain reaction (PCR) for detecting MRSA nasal colonization of infants was evaluated and compared to culture-based methods. The effect of skin decolonization in affected infants was studied. METHODS: Paired nasal swabs were collected from infants in our neonatal unit over a 12-month period (September 2007-2008). Colonization with MRSA was determined with a commercially available PCR method and compared to culture. RESULTS: A total of 696 paired nasal swabs were taken. Three infants were colonized at the beginning and were included. There were positive PCRs in 12 infants. Five infants cultured MRSA from a nasal swab at the same time. No infants were culture-positive when PCR was negative (sensitivity 100%, specificity 99% compared to culture). PCR results were available within 24 h. Five infants were PCR+ and isolated meticillin-sensitive Staphylococcus aureus. This organism gave a false-positive PCR result. Two infants transferred in on broad-spectrum antibiotics were PCR+ and negative by culture. Decolonization led to negative nasal PCR and culture in 4/5 infants to discharge. CONCLUSIONS: PCR methods are sensitive and specific for detection of MRSA colonization in newborn infants of all gestations with results 1-2 days before culture.

Osteonecrosis and spontaneous exfoliation of dental implants associated with oral bisphosphonate therapy: a case report.

Bisphosphonates (BPs) have long been used for the treatment of osteoporosis and diseases like bone malignancies, active Paget's disease of bone, severe osteogenesis imperfecta and fibrous dysplasia among others. They bond highly to the bone surface and inhibit bone resorption. As BPs have a long half-life in bone because of their irreversible binding to bone, patients retain their risk profile even after drug cessation. This property also explains the complications wherein the cessation of bone resorption leads to halt in bone turnover. Usually with alendronate the risk of bisphosphonate-related osteonecrosis of jaw (BRONJ) wears off after 12 months. Reporting of the development of BRONJ is commonly associated with the intravenous BPs. Invasive surgical procedure associated with the placement of implants has been shown to be a major reason for the occurrence or initiation of BRONJ in susceptible patients. The prognosis of implants placed in the jaws of patients under or past BP medication is still uncertain. The present case report describes a patient on long-term oral BP therapy with spontaneous exfoliation of implant supported bone due to osteonecrosis.

Focal Leptomeningeal Disease with Perivascular Invasion in EGFR-Mutant Non-Small-Cell Lung Cancer.

We report a previously undescribed pattern of brain metastases in patients with epidermal growth factor receptor-mutated non-small-cell lung cancer treated with tyrosine kinase inhibitors and radiation therapy. These highly distinct lesions appear to spread focally within the leptomeninges, with invasion along the perivascular spaces (FLIP). The survival of patients with FLIP was significantly better compared with patients with classic leptomeningeal disease (median survival, 21 versus 3 months; P = .003). It is unclear whether this pattern of growth is unique to epidermal growth factor receptor-mutated non-small-cell lung cancer.

Structure, genetic mapping, and function of the cytochrome P450 3A37 gene in the turkey (Meleagris gallopavo).

Cytochromes P450 (P450 for protein; CYP for gene) are a superfamily of membrane-bound hemoproteins that oxidize a large number of endogenous and exogenous compounds. Through oxidation reactions, these enzymes are often responsible for the toxic and carcinogenic effects of natural food-borne toxicants, such as the mycotoxin aflatoxin B1 (AFB1). Previous studies in our laboratory have shown that the extreme sensitivity of turkeys to AFB1 is in part explained by efficient hepatic P450-mediated epoxidation to the toxic and reactive metabolite the exo-AFB1-8,9-epoxide (AFBO). Using 3'-5'-rapid amplification of cDNA ends (RACE), we amplified CYP3A37 from turkey liver RNA, the E. coli-expressed protein which efficiently epoxidates AFB(1). Turkey CYP3A37 has an ORF of 1512 bp, and the protein is predicted to be 504 amino acids with 97% homology to chicken CYP3A37. The turkey gene is organized into 13 exons and 12 introns. A single nucleotide polymorphism in the 11th intron was used to assign CYP3A37 to turkey linkage group 10 (corresponding to chicken chromosome 14, GGA14). Because of the important role of P450s in the extreme sensitivity of turkeys to the toxic effects of AFB(1), this study will contribute to the identifying allelic variants of this important gene in poultry.

Multinucleate cell angiohistiocytoma: an uncommon mucosal tumour.

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon benign soft-tissue lesion with characteristic histological and immunohistochemical features. It is unclear if it represents a benign neoplasm or a reactive/inflammatory process. The overwhelming majority of these tumors have been described on cutaneous surfaces. One case has been reported on the skin of the lip. This is the first documentation of MCAH within the oral cavity. The clinical presentation, histopathological features and immunohistochemical reactivity pattern are described. Because of the benign nature of this lesion, a conservative approach is recommended in its management. Surgical excision appears to be curative.

Predicting relapse in Crohn's disease: a biopsychosocial model.

BACKGROUND: Crohn's disease (CD) is a chronic relapsing inflammatory bowel disorder. Both biological and psychosocial factors may modulate the illness experience. AIM: The aim of this study was to identify clinical, biological and psychosocial parameters as predictors of clinical relapse in quiescent CD. METHODS: Patients in medically induced remission were followed prospectively for 1 year, or less if they relapsed. Disease characteristics were determined at baseline. Serum cytokines, anti-Saccharomyces cerevisiae antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate and intestinal permeability were measured every 3 months. Psychological distress, perceived stress, minor life stressors and coping strategies were measured monthly. A time-dependent multivariate Cox regression model determined predictors of time to relapse. RESULTS: 101 patients (60 females, 41 males) were recruited. Fourteen withdrew and 37 relapsed. CRP (HR = 1.5 per 10 mg/l, 95% CI 1.1 to 1.9, p = 0.007), fistulising disease (HR = 3.2, 95% CI, 1.1 to 9.4, p = 0.04), colitis (HR = 3.5 95% CI 1.2 to 9.9, p = 0.02) and the interaction between perceived stress and avoidance coping (HR = 7.0 per 5 unit increase for both scales, 95% CI 2.3 to 21.8, p = 0.003) were predictors of earlier relapse. CONCLUSIONS: In quiescent CD, a higher CRP, fistulising disease behaviour and disease confined to the colon were independent predictors of relapse. Moreover, patients under conditions of low stress and who scored low on avoidance coping (ie, did not engage in social diversion or distraction) were least likely to relapse. This study supports a biopsychosocial model of CD exacerbation.

Diagnostic Impact of Intracranial Vessel Wall MRI in 205 Patients with Ischemic Stroke or TIA.

BACKGROUND AND PURPOSE: Secondary prevention of ischemic stroke depends on determining the cause of the initial ischemic event, but standard investigations often fail to identify a cause or identify multiple potential causes. The purpose of this study was to characterize the impact of intracranial vessel wall MR imaging on the etiologic classification of ischemic stroke. MATERIALS AND METHODS: This was a single-center, retrospective study of 205 consecutive patients who were referred for vessel wall MR imaging to clarify the etiology of an ischemic stroke or TIA. An expert panel classified stroke etiology before and after incorporating vessel wall MR imaging results using a modified Trial of Org 10172 in Acute Stroke Treatment system. We measured the proportion of patients with an altered etiologic classification after vessel wall MR imaging. RESULTS: The median age was 56 years (interquartile range = 44-67 years), and 51% (106/205) of patients were men. Vessel wall MR imaging altered the etiologic classification in 55% (112/205) of patients. The proportion of patients classified as having intracranial arteriopathy not otherwise specified decreased from 31% to 4% (64/205 versus 9/205; P < .001) and the proportion classified as having intracranial atherosclerotic disease increased from 23% to 57% (48/205 versus 116/205; P < .001). Conventional work-up classification as intracranial arteriopathy not otherwise specified was an independent predictor of vessel wall MR imaging impact (OR = 8.9; 95% CI, 3.0-27.2). The time between symptom onset and vessel wall MR imaging was not a predictor of impact. CONCLUSIONS: When vessel wall MR imaging is performed to clarify the etiology of a stroke or TIA, it frequently alters the etiologic classification. This is important because the etiologic classification is the basis for therapeutic decision-making.

Heterotopic pregnancy with spontaneous intrauterine conception: a rare clinical entity with diagnostic dilemma.

Twenty-one years old primigravida presented to emergency with amenorrhoea for 2 months and complaints of severe abdominal pain for few hours. The pain was associated with 2 episodes of fainting attacks in emergency during the period of observation. Viable intrauterine pregnancy of 8-9 weeks along with collection of fluid in the Pouch of Douglas was detected by ultrasound examination and on laparotomy ectopic pregnancy was confirmed with haemoperitoneum of 2 litres with 500gms of clots. Histopathology report confirmed the tubal ectopic pregnancy and postlaparotomy, transvaginal sonography confirmed the salvage of the intrauterine pregnancy. Despite massive haemoperitoneum, the pregnancy continued till 40+6 weeks with uneventful antenatal period. She underwent emergency caesarean section for meconium stained liquor with foetal distress and delivered of an alive healthy female of 2.5 kg with good Apgar score.

Comparison of Sagittal FSE T2, STIR, and T1-Weighted Phase-Sensitive Inversion Recovery in the Detection of Spinal Cord Lesions in MS at 3T.

BACKGROUND AND PURPOSE: Determining the diagnostic accuracy of different MR sequences is essential to design MR imaging protocols. The purpose of the study was to compare 3T sagittal FSE T2, STIR, and T1-weighted phase-sensitive inversion recovery in the detection of spinal cord lesions in patients with suspected or definite MS. MATERIALS AND METHODS: We performed a retrospective analysis of 38 patients with suspected or definite MS. Involvement of the cervical and thoracic cord segments was recorded on sagittal FSE T2, STIR, and T1-weighted phase-sensitive inversion recovery sequences independently by 2 readers. A consensus criterion standard read was performed with all sequences available. Sensitivity, specificity, and interobserver agreement were calculated for each sequence. RESULTS: In the cervical cord, the sensitivity of T1-weighted phase-sensitive inversion recovery (96.2%) and STIR (89.6%) was significantly higher (P < .05) than that of FSE T2 (50.9%), but no significant difference was found between T1-weighted phase-sensitive inversion recovery and STIR. In the thoracic cord, sensitivity values were 93.8% for STIR, 71.9% for FSE T2, and 50.8% for T1-weighted phase-sensitive inversion recovery. Significant differences were found for all comparisons (P < .05). No differences were detected in specificity. Poor image quality and lower sensitivity of thoracic T1-weighted phase-sensitive inversion recovery compared with the other 2 sequences were associated with a thicker back fat pad. CONCLUSIONS: The use of an additional sagittal sequence other than FSE T2 significantly increases the detection of cervical and thoracic spinal cord lesions in patients with MS at 3T. In the cervical segment, both STIR and T1-weighted phase-sensitive inversion recovery offer high sensitivity and specificity, whereas in the thoracic spine, STIR performs better than T1-weighted phase-sensitive inversion recovery, particularly in patients with a thick dorsal fat pad.

Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma.

The Oncology Gold Standard (OGS) Expert Group on renal cell carcinoma (RCC) developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc) RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of "Take Home Messages" at the end is a convenient tool for busy practitioners.

Perturbations of liver plasma membranes induced by Ca2+ are detected using a fatty acid spin label and adenylate cyclase as membrane probes.

Ca2+ decreased the lipid fluidity of rat liver plasma membranes labeled with 5-nitroxide stearate, I(12,3), as indicated by the order parameter (S). These effects form a reversible, saturable process with an association constant of 1 x 10(3) M-1. Arrhenius-type plots of S indicated that the lipid phase separation, present in the external leaflet of native membranes between 28 and 19 degrees C, is perturbed by mM Ca2+ such that the high temperature onset is elevated to 32-34 degrees C. Fluoride-stimulated adenylate cyclase was similarly inhibited by Ca2+ (ID50 = 1 mM) for the enzyme in membrane-bound or solubilized states. The glucagon-stimulated activity was more sensitive to Ca2+ inhibition with an ID50 of 0.2 mM. These inhibitory effects are due neither to perturbations of glucagon binding to its receptor nor to fluidity changes, but are instead attributed to direct Ca2+-enzyme interactions. Such binding desensitizes the enzyme to fluidity alterations induced by temperature elevation or benzyl alcohol addition. With Ca2+, Arrhenius plots of glucagon-stimulated activity indicated breaks at 32 and 16 degrees C, whereas those of fluoride-stimulated activity showed one break at 17 degrees C. Without Ca2+, Arrhenius plots exhibited one break at 28 degrees C for glucagon-stimulated activity, whereas fluoride-stimulated plots were linear. We propose that Ca2+ achieves these effects through asymmetric perturbations of the membrane lipid structure.

Taxol-DNA interactions: fluorescence and CD studies of DNA groove binding properties of taxol.

Taxol is perhaps the most successful drug used for the treatment of various cancers. Comprehensive literature accumulated on therapeutics of the drug has indicated numerous side effects. In this paper, by use of fluorescence spectroscopy, it is shown that taxol binds to DNA with an affinity constant (Ka) of 1.08 x 10(7) M-1. This binding is accompanied by a large 'red edge excitation shift' (REES) of fluorescence emission maximum in taxol-DNA complex. The results point to an interaction of taxol with its core eight-membered ring in the DNA groove and the three phenyl rings projecting away from the DNA. The drug encompasses about two base pairs of DNA upon binding to it. Systematic studies with taxol analogues confirms such a mode of binding. These interesting findings on hitherto unknown taxol-DNA interactions may have clinical implications in view of its large number of side effects and pharmacokinetics.