tbuckley/cabot-search huggingface dataset:
Environmental Correlation Analysis for Genes Associated with Protection against Malaria
Authors: Margaret J. Mackinnon, Carolyne Ndila, Sophie Uyoga, Alex Macharia, Robert W. Snow, Gavin Band, Anna Rautanen, Kirk A. Rockett, Dominic P. Kwiatkowski, Thomas N. Williams
Journal: Molecular Biology and Evolution (2016)

Genome-wide searches for loci involved in human resistance to malaria are currently being conducted on a large scale in Africa using case-control studies. Here, we explore the utility of an alternative approach—"environmental correlation analysis, ECA," which tests for clines in allele frequencies across a gradient of an environmental selection pressure—to identify genes that have historically protected against death from malaria. We collected genotype data from 12,425 newborns on 57 candidate malaria resistance loci and 9,756 single nucleotide polymorphisms (SNPs) selected at random from across the genome, and examined their allele frequencies for geographic correlations with long-term malaria prevalence data based on 84,042 individuals living under different historical selection pressures from malaria in coastal Kenya. None of the 57 candidate SNPs showed significant (P < 0.05) correlations in allele frequency with local malaria transmission intensity after adjusting for population structure and multiple testing. In contrast, two of the random SNPs that had highly significant correlations (P < 0.01) were in genes previously linked to malaria resistance, namely, CDH13, encoding cadherin 13, and HS3ST3B1, encoding heparan sulfate 3-O-sulfotransferase 3B1. Both proteins play a role in glycoprotein-mediated cell-cell adhesion which has been widely implicated in cerebral malaria, the most life-threatening form of this disease. Other top genes, including CTNND2 which encodes δ-catenin, a molecular partner to cadherin, were significantly enriched in cadherin-mediated pathways affecting inflammation of the brain vascular endothelium. These results demonstrate the utility of ECA in the discovery of novel genes and pathways affecting infectious disease.
The therapeutic benefit of extensive lymphadenectomy in advanced stage ovarian cancer
Authors: J. S. Berek, N. Karnik Lee, M. K. Cheung, K. Osann, A. Husain, N. N. Teng, D. S. Kapp, J. K. Chan
Journal: Journal of Clinical Oncology (2006)

15010 Background: To determine if extent of lymphadenectomy affects the disease-specific survival of women with advanced-stage ovarian cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 15,320 women with stage IIIB-IV disease, 763 (5.0%) had stage IIIB, 5,266 (34.4%) stage IIIC, and 9,291 (60.7%) had stage IV disease. The median age was 66 (range: 1–101). 13,251 (86.5%) were White, 1,049 (6.9%) Black, 716 (4.7%) Asian, and 304 (1.9%) were Other. Of the patients who underwent a lymphadenectomy, the median number of nodes resected was 6 (range: 1–90). We divided our study group 3 groups based on the extent of lymphadenectomy (0, &lt;10, 10–20, and &gt;20). In the overall study group, the extent of lymphadenectomy improved the survival from 21.1%, 40.5%, 45.1% to 46.0%, respectively (p &lt; 0.001). Patients with stage IIIB, IIIC, and IV disease had an improvement in survival associated with lymphadenectomy (see table ). In patients with non-clear cell epithelial carcinoma, the extent of lymphadenectomy was associated with improved survivals 20.9%, 39.8%, 45.4%, and 45.9%, respectively (p &lt; 0.0001). Moreover, those with clear cell cancers (p = 0.0001), germ cell (p = 0.001) and sarcomas of the ovary (p = 0.02) also had a survival benefit; however no benefit was demonstrated in sex cord stromal tumors (p = 0.99). In multivariate analysis, a more extensive lymphadenectomy remained significant as an independent prognostic factor for improved survival after adjusting for all other independent prognostic factors including age, year of diagnosis, surgery, histology, stage, and grade. Conclusions: Our findings suggest that the extent of lymphadenectomy improves the disease-specific survival of women with stage IIIB-IV ovarian cancer. This benefit was demonstrated in epithelial, germ cell, and sarcomas of the ovary. [Table: see text] No significant financial relationships to disclose.
Diabetes in Ramadan
Authors: Aamir Shahzad
Journal: Journal of the Royal Society of Medicine (2003)

Dr Qureshi (October 2002, JRSM1) offers advice on Ramadan fasting in people with diabetes. This is a complex issue, especially for Muslim doctors in whom the scientific facts tend to be mixed with religious considerations. I disagree with some of his ‘practical points’.

First, he has confused Muslim dietary laws with decrees on health. There is a consensus amongst Muslim jurists that non-halal products of permitted animals, though undesirable, may be used for medicinal purposes. Bovine insulin was freely used in Pakistan before Humulin became available. Even porcine products are acceptable provided the illness is life-threatening and alternatives are not available.

I have been unable to find any controlled study showing hypoglycaemic effects from traditional medicines such as karela (gourd) powder, or onion and garlic, in the amounts normally consumed. Onion and garlic, being regular ingredients of South Asian diet, are consumed daily by people from that region—who are more, not less, prone to diabetes than the white population of the UK.

‘Meditation and prayer tend to lower blood pressure’ is another statement that should not be taken at face value. Muslims do not all meditate or pray to the same degree; the individual effects vary an such modalities or their results have not been quantified to predict the necessary adjustment of antihypertensive medicine. Regarding drug therapy in Ramadan, glucosidase inhibitors are the safest drugs for type 2 diabetics and should be used with reduced doses of metformin and sulphonylureas to minimize the risk of glucose fluctuation and acidosis.

Finally, fasting does not always improve diabetes but can make it worse. This has to do with the nature of the disease and patient psychology. Fasting-induced ketosis is a real danger, as is dehydration. Patients may self-adjust the drug timing so as to skip the fasting period. They may reduce or stop medication altogether in the belief that the glucose concentration will not rise in absence of meal and snacks (and God will take care of them during the holy act). They may over-eat at sehri (fast starting meal) to fill up for the day and at iftari (fast ending meal) because of hunger.

To achieve a suitable dose and timing adjustment is not easy. By the time a suitable regimen is devised, most of the Ramadan is gone. For these reasons diabetologists in predominantly Muslim countries discourage patients from fasting unless their disease is well controlled and the patients are well motivated to adapt to changes in their treatment.
Prophylactic oral glutamine for docetaxel or paclitaxel associated taste alterations in cancer patients: A randomised, parallel, placebo-controlled, double-blind study
Authors: F. Strasser, R. Demmer, C. Boehme, S. Schmitz, B. Thuerlimann, T. Cerny, S. Gillessen
Journal: Journal of Clinical Oncology (2007)

9104 Background: Taste alterations (TA) can occur as side-effects of taxane-based chemotherapy (T-Ch) and studies suggest that glutamin can reduce neurotoxicity. We compared in patients (pts) with a first time T-Ch oral glutamin (G) with placebo (P) for occurrence and severity of TA. Methods: Pts were randomised for 30g per day G or P (maltodextrin) (Baxter, Switzerland) from the first day of T-Ch. Subjective TA (dysgeusia) was measured daily by VAS, at baseline 3 times. On each cycle of T-Ch, objective (sour, sweet, salty, bitter) and subjective (4-categorical scale of 4 tastes) TA, and toxicity (NCI CTC V.3) were assessed. Stomatitis and zinc deficiency were screened for and treated. Of 47 pts receiving at least one day G or P, three (2 G, 1 P) died to tumor progression and three (2 G, 1 P) withdraw consent in the first cycle of T-Ch. For primary outcomes, repeated dysgeusia scores were analyzed by linear mixed model and repeated binary values of each objective taste item by generalized estimating equation using logit link function. Results: G (n=21) and P (n=20) pts groups were comparable for demographics (f:m 5:16, median age 67 [49,83], 9 prostate, 3 lung, 3 breast, 6 other cancer; 8:12, 63 [40,73], 2, 6, 6, 6), and T-Ch drug (docetaxel 11/paclitaxel 10; 7/13), schedule (weekly 18/3-weekly 3; 14/6), or goal (adjuvant 1/palliative 20; 5/15). At baseline, average median dysgeusia was 11 in both groups (0,90; SD 23. 0,99; 22), 4 tastes were recognized by 12, 16, 13, and 15 pts in G (n=16) and 16, 19, 17, 19 in P (n=20). Study duration was 73 days for G (median; 4, 385) and 74 for P (7, 187). 19 of 39 pts (11 G, 8 P) developed peripheral neuropathy G1 or G2, none G3. Maximal (mean) dysgeusia was 31 (1, 100) in G and 33 (4, 74) in P; increase from baseline was 20 (1, 100) and 22 (1, 63). No effect of G or P on dysgeusia was detected (p=ns), linear time effect was p=0.46. Baseline dysgeusia effect was significant (p&lt;0.0001), two group analysis (dysgeusia =11) did not alter results. Objective taste tests (no baseline effect) or subjective TA were not different, as were adverse events. Conclusions: Oral glutamin at the dose given did not decrease subjective taste disturbances or altered taste perception associated with T-Ch compared to placebo. No significant financial relationships to disclose.
Intravenous immune globulin in the treatment of patients with systemic lupus erythematosus and end-stage renal disease.
Authors: B N Becker, H Fuchs, R Hakim
Journal: Journal of the American Society of Nephrology (1995)

Intravenous immune globulin (IVIg) has been advocated as efficacious therapy for a variety of disorders including idiopathic thrombocytopenic purpura and Kawasaki disease. Several reports have also documented the effectiveness of IVIg in systemic lupus erythematosus (SLE). Two patients with symptomatic SLE and ESRD were treated with IVIg. Both patients tolerated IVIg administration well and demonstrated clinical and serologic improvement. Both individuals also experienced a transient decline in serum albumin concentration with IVIg treatment. The mechanisms by which IVIg might have effected improvement in these patients are varied and are likely related to the immunomodulatory actions of IVIg. The reversible change in albumin concentration seen in these individuals may be secondary to abrupt alterations in oncotic homeostasis. Despite this unusual effect, the documented improvement in these patients suggests that IVIg therapy may be of benefit in patients with active SLE and ESRD. Further studies are warranted to examine the mechanisms by which IVIg may exert its therapeutic effect.
Ethical and Societal Questions Loom Large as Gene Editing Moves Closer to the Clinic
Authors: Tracy Hampton
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fall in 1:1 nursing ratios in neonatal ICUs is linked to higher death rate
Authors: Jacqui Wise
Journal: BMJ (2016)

Provision of one to one nursing care for very sick and premature newborns fell by about a third from 2008 to 2012 in England, while the in hospital mortality rate in tertiary level neonatal intensive care units increased, research published in the Archives of Disease in Childhood (Fetal and Neonatal Edition ) has found.1

The British Association of Perinatal Medicine recommends a 1:1 nurse to patient ratio for all infants receiving neonatal intensive care in the …
Enhanced Staging and All Chemotherapy Preoperatively in Patients with Potentially Resectable Gastric Carcinoma
Authors: Jaffer A. Ajani, Paul F. Mansfield, Patrick M. Lynch, Peter W. Pisters, Barry Feig, Pamela Dumas, Douglas B. Evans, Issac Raijman, Kristin Hargraves, Stephen Curley, David M. Ota
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Patients with local-regional gastric carcinoma have a low rate of curative resection (R0) because of the advanced stage at diagnosis and suboptimal clinical staging. This study was designed to improve clinical staging with the use of laparoscopy and endoscopic ultrasonography (EUS) and to improve R0 resection rates and tolerance by delivering all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. PATIENTS AND METHODS: All patients with histologic proof of localized adenocarcinoma of the stomach underwent a staging laparoscopy before registration. EUS was performed when feasible. The intention was to administer up to five courses of preoperative chemotherapy consisting of fluorouracil (500 mg/m 2 /d as a continuous infusion on days 1 through 5 and as a bolus on days 12 and 19), interferon alfa-2b (3 million units subcutaneously three times a week for 3 weeks), and cisplatin (15 mg/m 2 /d as a bolus on days 1 through 5). After chemotherapy, surgery was attempted to remove the primary and regional lymph nodes. Clinical response and EUS staging were correlated with surgical pathology. The feasibility of this approach, resection rates, patient survival, and patterns of failure also were assessed. RESULTS: All 30 patients enrolled were assessed for toxicity, response, and survival. Nineteen men and 11 women were enrolled. The median number of courses delivered per patient was three (range, one to five courses). Fourteen patients (47%) received all five preoperative courses of chemotherapy. The overall clinical response rate was 34%. Twenty-nine patients (97%) underwent attempted resection. Twenty-five (83%) had an R0 resection. Two patients (7%) had no evidence of carcinoma in the surgical specimen, and three had only microscopic carcinoma (≥ 90% necrosis). Posttreatment EUS findings did not correlate well with surgical pathology. The median duration of follow-up was 30 months (range, 5 months to 65+ months). The median survival time for 30 patients, calculated by the Kaplan-Meier method, was 30 months (range, 5 months to 65+ months). There were no cases of grade 4 toxicity. CONCLUSION: It is feasible to administer prolonged preoperative therapy in patients with potentially resectable gastric carcinoma. Enhanced staging with laparoscopy and EUS helped in proper selection of patients and better characterization of the stage.
원저 / 간세포암 진단을 위한 세침흡인 세포학적 검사의 필요성과 안전성
Authors: 정성문(Sung Moon Jung), 이진옥(Jin Ok Lee), 정숙향(Sook Hyang Jung), 한철주(Chul Joo Han), 김유철(Yoo Chul Kim), 김창민(Chang Min Kim), 이진오(Jin Oh Lee), 유성재(Sung Jae Yoo), 송용환(Yong Hwan Song), 이병희(Byung Hee Lee), 김기완(Gee Wan Kim), 조경자(Gyung Ja Jo), 이승숙(Seung Sook Lee)
Journal: Clinical and Molecular Hepatology (2000)

Backgrounds/Aims: The fine-needle aspiration (FNA) is a useful method for diagnosis of hepatocellular carcinoma (HCC). The aims of our study are to assess diagnostic accuracy of FNA, to define proper indications of FNA for diagnosis of HCC, and to evaluate the complications of FNA. Subjects and Methods: To assess diagnostic accuracy we compared the results of preoperative FNA with postoperative pathology in 38 resected cases with primary liver cancer. To define proper indications and complications of FNA, we prospectively followed 138 patients received FNA for their liver tumors which were suspicious of primary liver tumor. Results : The sensitivity, specificity, positive and negative predictive values of FNA were 100%, 97%, 100% and 66% respectively. All patients with serum alpha-fetoprotein (AFP) level over 1000 ng/ml were having HCC on FNA result. Among 36 patients with AFP level ranged 15-1000 ng/ml and hypervascular mass on angiography, 96% were having HCC. Among 50 patients with normal AFP level and hypervascular mass on angiography, 92% were having HCC. The major complications after FNA such as hemoperitoneum, pneumothorax, and iatrogenic arterioportal shunt developed in 2%, 2%, and 7% of subjects, respectively. We did not find any case of needle-tract seeding of cancer during a mean 4.7 months of follow-up. Conclusions: Although the FNA is an accurate method for diagnosis of HCC, FNA was usually not indicated for patients with serum AFP level over 1000 ng/ml or patients with hypervascular mass on angiography when they were suspected of having primary liver cancer. Major complications were hemoperitoneum, pneumothorax and iatrogenic arterioportal shunt. Iatrogenic arterioportal shunt may influence the efficacy of subsequent transcatheter arterial embolization.
Abstract 037: Ace Inhibitor Use by Older Adults is Associated with Improved Functional Responses to Exercise
Authors: Thomas W Buford, Todd M Manini, Fang-Chi Hsu, Matteo Cesari, Stephen D Anton, Susan Nayfield, Randall S Stafford, Timothy S Church, Marco Pahor, Christy S Carter
Journal: Circulation (2012)

Introduction: Functional status, assessed objectively by measures of physical performance, is a strong predictor of cardiovascular events in older adults. Angiotensin converting enzyme (ACE) inhibitors may further enhance the beneficial effects of exercise training on the functional status of older adults, but studies are lacking to confirm. The objective of this study was to assess the association of ACE inhibitor use with exercise-derived improvements in physical function among physically-limited older adults. Hypothesis: Older adults who used ACE inhibitors would have larger improvements in physical function in response to exercise than non-users. Methods: This study is a secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study. LIFE-P investigated the effects of 12-month interventions consisting of either structured physical activity or health education to promote successful aging on 424 adults aged 70-89 years at risk for becoming physically disabled. This analysis compared change in outcome measures at 6- and 12-months among participants who (1) did not use anti-hypertensive drugs, (2) used ACEi, and (3) used anti-hypertensive drugs excluding ACEi. The primary outcome measures were change in performance on a battery of short-duration mobility tasks (SPPB) and walking speed during a 400 meter test. Results: A significant medication by intervention interaction existed for SPPB (p=0.018). PA improved the adjusted SPPB score among ACEi users (p&lt;0.001) and users of other anti-hypertensive drugs (p=0.005) but not among anti-hypertensive non-users (p=0.911). Adjusted SPPB changes at 12 months were 0.95 points among ACEi users, 0.77 points among users of other anti-hypertensive drugs, and -0.08 points among anti-hypertensive non-users. For walking speed, the medication by intervention interaction was not significant (p=0.178), but a trend existed for the medication by intervention by visit interaction (p=0.094). PA significantly improved the adjusted walking speed of ACEi users (p&lt;0.001) but did not improve walking speed among the other two groups across study visits. At 12 months adjusted changes were 0.06 m/sec among ACEi users, 0.05 m/sec among anti-hypertensive non-users, and 0.02 m/sec among users of other anti-hypertensives. Conclusions: Among older adults at risk for disability, exercise-derived improvements in physical function were greatest among ACEi users. Future prospective studies are needed to confirm the true efficacy of ACE inhibitors in improving older adults’ functional responses to exercise.
A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.
Authors: R B Buchanan, R W Blamey, K R Durrant, A Howell, A G Paterson, P E Preece, D C Smith, C J Williams, R G Wilson
Journal: Journal of Clinical Oncology (1986)

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.
Pediatric phase I trial and pharmacokinetic study of P-glycoprotein inhibitor, tariquidar, in combination with doxorubicin, vinorelbine or docetaxel
Authors: E. Fox, B. C. Widemann, C. C. Chen, O. Van Tellingen, S. Riches, G. Boniface, D. Norris, S. Bates, T. Fojo, F. M. Balis
Journal: Journal of Clinical Oncology (2004)

8541 Background: P-glycoprotein (Pgp), an ATP-dependent membrane transporter present in normal tissues, confers multidrug resistance in cancer cells. Tariquidar (TQ) blocks Pgp by inhibiting ATP binding and hydrolysis. Objectives: Assess toxicity, optimal dose, pharmacokinetics (PK) and pharmacodynamics of TQ in children with solid tumors and assess toxicity and PK of anticancer drugs (AD) in combination with TQ. Methods: TQ (1 [n=4], 1.5 [n=6], or 2 [n=5] mg/kg IV) was given alone on d 1 and with doxorubicin (DOXO, 50 mg/m2, n=10), docetaxel (75 mg/m2, n=4), or vinorelbine (20 mg/m2 d 3 & 10, n=1) on d 3. Plasma PK samples from d 1 & 3 were assayed for TQ by LC/MS/MS and DOXO by LC-fluorescent detection. Pgp function in vivo was assessed pre & post TQ using rhodamine uptake in CD56+ blood cells 24 h post TQ by flow cytometry (n=12) and 99mTc-sestamibi scintigraphy (n=6) immediately ater TQ. Results: 15 children (age 2–18, median 13) with sarcoma (n=8), adrenocortical carcinoma (n=3) or other (n=4) were enrolled. TQ was well tolerated at all dose levels. Delayed neutrophil recovery (n=2), grade 3 thrombocytopenia from docetaxel (n=1) and grade 3 mucositis (n=3) were prominent AD toxicities. AD toxicities may be more severe at the 2 mg/kg TQ dose. PK parameters for TQ alone are presented below. DOXO clearance (CL, n=8) was 400±150 mL/min/m2 given with TQ. Inhibition of rhodamine efflux in CD56+ cells was 54, 62, and 79% of maximum at the 1, 1.5 and 2 mg/kg doses of TQ. Sestamibi uptake increased by 1.7- to 4.1-fold (median, 2.6-fold) in liver and 1.2 to 1.4-fold in tumor (n=2) after TQ. Conclusions: 2 mg/kg TQ is well tolerated in children. TQ CL may be dose dependent, and at 2 mg/kg TQ CL is comparable to CL in adults. DOXO CL was comparable to published results. Pgp function in CD56+ blood cells is inhibited for ≥24 h. TQ also enhanced retention of sestamibi in liver and in some tumors. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration QLT, Inc.; Xenova Group, plc QLT, Inc.; Xenova Group, plc Xenova Group, plc