tbuckley/cabot-search huggingface dataset:
Metabolic effects of enteral formula feeding in alcoholic hepatitis
Authors: Santos Soberon, Mary P. Pauley, Richard Duplantier, Angelita Fan, Charles H. Halsted
Journal: Hepatology (1987)

The etiology of malnutrition and the metabolic effect of aggressive nutritional support by enteral feeding were evaluated in patients with moderately severe alcoholic hepatitis. Among 21 patients presenting with jaundice, ascites, coagulopathy and low grade encephalopathy, the mean digestibilities (intake – fecal excretion/intake × 100) of total energy and fat were subnormal at 74.6 ± 2.9 and 64.5 ± 4.4%, respectively, and nitrogen balance was negative in half the patients with a mean value of +0.74 gm per day ± 1.2. Based on initial ad libitum intake of hospital diet, patients were grouped as six patients with adequate caloric intake who underwent a repeated 3-day balance study to assess the effect of hospitalization (Group I) and eight anorectic patients who underwent a repeat balance study during constant nasoduodenal infusion of the liquid formula Isocal-HCN in an amount sufficient to provide 35 kcal per kg ideal body weight (Group II). During the initial phase of hospital tray diet, the mean digestibilities of energy, fat, protein and carbohydrate, and the mean nitrogen balance were similar in each group. The digestibilities of each diet constituent and nitrogen balance were similar in both phases of hospital tray diet in patients in Group I. On the other hand, the infusion of Isocal-HCN to patients in Group II resulted in significant increases over their baseline values in intakes of energy and protein and in digestibilities of energy, fat and protein, and in a 5-fold increase in nitrogen balance. Provision of essential nutrients by enteric infusion had no effect on fluid balance or degree of encephalopathy. These short-term studies provide a metabolic basis for enteric formula feeding in improving the intestinal absorption and nitrogen balance of anorectic patients with alcoholic hepatitis.
Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer
Authors: G Luporini, S Barni, E Marchi, L Daffonchio
Journal: European Respiratory Journal (1998)

Nonproductive cough is a frequent and distressing symptom in patients with lung cancer, and it is not even relieved by palliative chemotherapy. A double-blind, randomized clinical trial regarding the treatment of nonproductive cough was performed in 140 adults with primary lung cancer or metastatic cancer of the lungs. The therapeutic efficacy and the tolerability of a 7-day treatment with levodropropizine drops (75 mg t.i.d.) were evaluated in comparison with dihydrocodeine drops (10 mg t.i.d.; 7 days). Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall estimate of antitussive efficacy. Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence. Subjective cough severity was significantly reduced during treatment with either levodropropizine and dihydrocodeine, the antitussive effect and its time-profile being similar for both drugs. Also, according to the investigator's evaluation, both levodropropizine and dihydrocodeine produced a significant decrease in cough severity. Concurrently with the relief of cough, the number of night awakenings was decreased significantly by both drugs, with no difference between the two treatments. No change in laboratory test values was considered clinically relevant, and vital signs were not clinically affected. The number of patients reporting adverse events was similar in the levodropropizine (n=6) and dihydrocodeine (n=4) group. However, the percentage of patients experiencing somnolence in the group receiving levodropropizine (8%) was significantly lower as compared with that of the dihydrocodeine group (22%). These results confirm the antitussive effectiveness of levodropropizine and suggest a more favourable benefit/risk profile when compared to dihydrocodeine.
<b> <i>In vitro</i> </b> and <b> <i>In vivo</i> </b> Activity of the Nuclear Factor-κB Inhibitor Sulfasalazine in Human Glioblastomas
Authors: Pierre A. Robe, Mohamed Bentires-Alj, Marianne Bonif, Bernard Rogister, Manuel Deprez, Heddi Haddada, Minh-Tuan Nguyen Khac, Olivier Jolois, Kadir Erkmen, Marie-Paule Merville, Peter M. Black, Vincent Bours
Journal: Clinical Cancer Research (2004)

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment.
Chemoprevention of Primary Liver Cancer: A Randomized, Double-Blind Trial in Linxian, China
Authors: C.-X. Qu, F. Kamangar, J.-H. Fan, B. Yu, X.-D. Sun, P. R. Taylor, B. E. Chen, C. C. Abnet, Y.-L. Qiao, S. D. Mark, S. M. Dawsey
Journal: JNCI Journal of the National Cancer Institute (2007)

Primary liver cancer is a common malignancy with a dismal prognosis. New primary prevention strategies are needed to reduce mortality from this disease. We examined the effects of supplementation with four different combinations of vitamins and minerals on primary liver cancer mortality among 29450 initially healthy adults from Linxian, China. Participants were randomly assigned to take either a vitamin–mineral combination ("factor") or a placebo daily for 5.25 years (March 1986–May 1991). Four factors (at doses one to two times the US Recommended Daily Allowance)—retinol and zinc (factor A); riboflavin and niacin (factor B); ascorbic acid and molybdenum (factor C); and beta-carotene, alpha-tocopherol, and selenium (factor D)—were tested in a partial factorial design. The study outcome was primary liver cancer death occurring from 1986 through 2001. Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of liver cancer death with and without each factor. All P values are two-sided. A total of 151 liver cancer deaths occurred during the analysis period. No statistically significant differences in liver cancer mortality were found comparing the presence and absence of any of the four intervention factors. However, both factor A and factor B reduced liver cancer mortality in individuals younger than 55 years at randomization (HR = 0.59, 95% CI = 0.34 to 1.00, and HR = 0.54, 95% CI = 0.31 to 0.93, respectively) but not in older individuals (HR = 1.06, 95% CI = 0.71 to 1.59, and HR = 1.12, 95% CI = 0.75 to 1.68, respectively). Factor C reduced liver cancer death, albeit with only borderline statistical significance in males (HR = 0.70, 95% CI = 0.47 to 1.02) but not in females (HR = 1.30, 95% CI = 0.72 to 2.37). Cumulative risks of liver cancer death were 6.0 per 1000 in the placebo arm, 5.4 per 1000 in the arms with two factors, and 2.4 per 1000 in the arm with all four factors. None of the factors tested reduced overall liver cancer mortality. However, three factors reduced liver cancer mortality in certain subgroups.
Addiction: A Disease of Learning and Memory
Authors: Steven E. Hyman
Journal: American Journal of Psychiatry (2005)

If neurobiology is ultimately to contribute to the development of successful treatments for drug addiction, researchers must discover the molecular mechanisms by which drug-seeking behaviors are consolidated into compulsive use, the mechanisms that underlie the long persistence of relapse risk, and the mechanisms by which drug-associated cues come to control behavior. Evidence at the molecular, cellular, systems, behavioral, and computational levels of analysis is converging to suggest the view that addiction represents a pathological usurpation of the neural mechanisms of learning and memory that under normal circumstances serve to shape survival behaviors related to the pursuit of rewards and the cues that predict them. The author summarizes the converging evidence in this area and highlights key questions that remain.
ON THE PERMANENT LIFE OF TISSUES OUTSIDE OF THE ORGANISM
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1912)

In two series of experiments made at the end of 1911 and at the beginning of 1912, new techniques were developed with the view of investigating the problem of prolonging indefinitely the life of tissues isolated from the organism. These techniques are far from perfect and will doubtless be modified in the future. But they have already permitted the establishment of new facts. Fragments of connective tissue have been kept in vitro in a condition of active life for more than two months. As a few cultures are now eighty-five days old and are growing very actively, it is probable that, if no accident occurs, the life of these cultures will continue for a long time. In some cases the rate of growth of the tissues increased in direct ratio to the age of the culture. Fragments of heart pulsated rhythmically at the beginning of the third month of their life in vitro. These facts show that experiments made with these or with more perfect techniques and followed over long periods of time may lead to the solution of the problem of permanent life of tissues in vitro, and give important information on the characters acquired by tissues liberated from the control of the organism from which they were derived.
Factors influencing age at diagnosis of primary ciliary dyskinesia in European children
Authors: C.E. Kuehni, T. Frischer, M-P.F. Strippoli, E. Maurer, A. Bush, K.G. Nielsen, A. Escribano, J.S.A. Lucas, P. Yiallouros, H. Omran, E. Eber, C. O'Callaghan, D. Snijders, A. Barbato
Journal: European Respiratory Journal (2010)

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged < 20 yrs. Reported cases per million children (for 5-14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p < 0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p < 0.001). This strongly correlated with general government expenditures on health (p < 0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.
Potential Pitfalls in the Use of Surrogate Endpoints in Colorectal Adenoma Chemoprevention
Authors: B. Levin
Journal: JNCI Journal of the National Cancer Institute (2003)

Colorectal cancer is the second most common cause of cancer death for both men and women in the United States (1). Understanding the relationship between adenomatous polyps and colorectal carcinoma is important in evaluating the effectiveness of chemoprevention. The relationship is complex, with the adenoma-to-carcinoma pathway characterized by a series of genetic alterations involving a number of genes, including APC, K-RAS, DCC, and p53 (2). In colorectal cancers, frequent loss of heterozygosity at multiple chromosomal loci, including 5q, 17p, and 18q, is observed. Such lesions are classified as microsatellite stable. Recent attention has also focused on an alternative pathway involved in the pathogenesis of colorectal cancer that accounts for 15%–20% of colorectal cancers, including hereditary non–polyposis colorectal cancer. This alternative pathway involves microsatellite instability and is also associated with serrated adenomas, hyperplastic aberrant crypt foci, and hyperplastic polyps (3). For asymptomatic average-risk individuals, the prevalence of adenomatous polyps ranges from 24%–47% (4). The risk of developing a carcinoma from an adenoma is related to its histologic type: tubular histology is associated with a 5% risk, tubulo-villous histology with a 15%–20% risk, and villous histology with up to a 50% risk. Adenoma size is also an important predictor of malignant potential. The risk of developing a carcinoma is approximately 1% for lesions less than 0.5 mm in diameter, 5% for lesions between 6 and 9 mm in diameter, and 20% for lesions greater than 1 cm in diameter (5). The National Polyp Study followed more than 2600 patients, who had all adenomas removed at initial colonoscopy, with surveillance colonoscopy at 1 and 3 years or at 3 years only. Reduction in colorectal cancer incidence was 76%–90% after colonoscopic polypectomy, compared with that in historical reference groups (6). Reduction in the incidence of colorectal cancer in a population that has undergone repeated fecal occult blood test screening is attributable in large measure to colonoscopic intervention (7). Experimental and observational studies support the use of adenomas as surrogate intermediate markers for colorectal cancer. In a population-based study, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, were associated with reduced risk of colorectal neoplasia, including adenomas, and with reduced colorectal cancer incidence (8). Approval of celecoxib (by the U.S. Food and Drug Administration [FDA]) for the
Cyclosporin for steroid‐dependent asthma
Authors: A. Szczeklik, E. Nizankowska, R. Dworski, B. Domagala, G. Pinis
Journal: Allergy (1991)

We used cyclosporin to treat 12 adult patients with severe bronchial asthma who had been on systemic steroids for an average of 16 years. During the baseline period, lasting 4-6 months, therapy with high doses of inhaled beclamethasone, aminophylline and salbutamol was standardized and a minimum necessary dose of systemic steroids was established. After 9 months' treatment with low-dose cyclosporin (average whole-blood trough levels of 105 ng/ml), in six patients the daily dose of oral prednisone could be reduced from mean 30 mg to mean 11 mg, while daily symptom scores and peak expiratory flows improved significantly. This was accompanied by a reduction in exacerbations of asthma. However, in six other patients attempts to taper the steroid doses were unsuccessful, and cyclosporin was stopped after 4 to 7 months. These preliminary results suggest that cyclosporin might be of benefit in some patients with steroid-dependent asthma.
Leukocyte‐Specific Protein 1: A Novel Regulator of Hepatocellular Proliferation and Migration Deleted in Human Hepatocellular Carcinoma
Authors: Kelly Koral, Shirish Paranjpe, William C. Bowen, Wendy Mars, Jianhua Luo, George K. Michalopoulos
Journal: Hepatology (2014)

Hepatocellular carcinoma (HCC) is the most commonly diagnosed form of liver cancer with high morbidity and mortality. Copy number variation (CNV) analysis of human HCC revealed that leukocyte‐specific protein 1 (LSP1) had the highest number of cases with CNV. LSP1, a F‐actin‐binding protein, is expressed in hematopoietic cells and interacts with kinase suppressor of Ras (KSR), a scaffold for the extracellular signal‐related kinase/mitogen‐activated protein kinase pathway. Expression of LSP1 in liver, and its role in normal hepatocellular function and carcinogenesis, remains unknown. Therefore, LSP1 messenger RNA and protein levels were analyzed in normal hepatocytes in culture, rat liver following partial hepatectomy (PHx), and hepatoma cell lines. In culture and after PHx, LSP1 increased after the termination of hepatocyte proliferation. To investigate LSP1 function in HCC, short hairpin RNA was utilized to stably knock down LSP1 expression in the JM1 rat hepatoma cell line. Loss of LSP1 in JM1 cells resulted in dramatic up‐regulation of cyclin D1 and phosphorylated ERK2, increased cell proliferation, and migration. Coimmunoprecipitation and immunofluoresence analysis displayed an interaction and colocalization between LSP1, KSR, and F‐actin in JM1 cells and liver during regeneration. Conversely, expression of LSP1 in the JM2 rat hepatoma cell line led to decreased proliferation. Enhanced expression of LSP1 in mouse hepatocytes during liver regeneration after injection of an LSP1 expression plasmid also led to decreased hepatocyte proliferation. Conclusion : LSP1 is expressed in normal hepatocytes and liver after PHx after termination of proliferation. In rat hepatoma cell lines and mouse liver in vivo , LSP1 functions as a negative regulator of proliferation and migration. Given the high frequency of LSP1 CNV in human HCC, LSP1 may be a novel target for diagnosis and treatment of HCC. (H epatology 2015;61:537‐547)
Long term experience using tenofovir and entecavir in the management of chronic hepatitis B in teaching hospital practice
Authors: P. A. Blaker, L. Lee, A. Ali, M. L. Wilkinson, T. Wong
Journal: Gut (2011)

<h3>Introduction</h3> In the first 12 months of treatment for chronic hepatitis B (CHB) infection tenofovir and entecavir have been reported as the most potent antiviral agents for HepBeAg-positive patients; tenofovir is the most effective for HepBeAg-negative patients.1 However, the long-term outcome of patients treated with these agents remains unclear. The authors report our teaching hospital experience of tenofovir and entecavir in the treatment of CHB. <h3>Methods</h3> All patients (n=112) treated for CHB between 2005 and 2010 with tenofovir (n=53) or entecavir (n=59) were identified from a pharmacy database and included in a retrospective audit. Levels of HepB DNA, ALT and albumin were collected at baseline and on a 3 monthly basis for the first 12 months and 6 monthly thereafter. The maximum duration of treatment was 48 months. <h3>Results</h3> Of patients receiving tenofovir 38% were HepBeAg-positive and 15% were cirrhotic versus 49% and 17% respectively in those treated with entecavir. Two patients in the tenofovir cohort seroconverted to e-antigen negative. The authors observed one case of early virological rebound (at week 27) in a treatment naïve patient prescribed entecavir through selection of lamivudine-associated mutations. The mean duration of treatment with tenofovir was 11 months (SD±7.8, range 3–48) versus 15 months (SD±9.4, range 0–30) for entecavir. In treatment experienced patients receiving tenofovir (n=35) the mean HepB DNA, ALT and albumin levels at baseline were; 4.39 log<sup>10</sup> IU/ml, 93.3 mmol/l and 44.9 mmol/l respectively, versus 5.10 log<sup>10</sup> IU/ml, 34 mmol/l and 47 mmol/l in treatment naïve patients. In treatment experienced patients prescribed entecavir (n=6) the mean HepB DNA, ALT and albumin levels at baseline were; 2.01 log<sup>10</sup> IU/ml, 26.6 mmol/l and 47.2 mmol/l respectively, versus 6.12 log<sup>10</sup> IU/ml, 107.2 mmol/l and 43.8 in treatment naïve patients. Overall there was no difference (p=0.83) in the mean time to undetectable viral load in patients treated with tenofovir (n=26, mean 5.19) versus entecavir (n=34, mean 6.18 months); including when subdivided into HepBeAg-positive (p=0.87) and HepBeAg-negative (p=0.80) groups. Improvement in synthetic function was observed following treatment with both agents in cirrhotic patients. <h3>Conclusion</h3> Viral load reduction to undetectable levels was observed in patients treated with either tenofovir or entecavir within 12 months with equivalent efficacy. The data suggest that either agent may be used in the management of CHB in both treatment experienced and naïve patients. However, the role of baseline resistance profiling in treatment naïve patients started on entecavir remains to be established.
A Lecture ON THE TREATMENT OF ECZEMATOUS PATIENTS: Delivered at the Medical Graduates' College and Polyclinic, London
Authors: E. G. Little
Journal: BMJ (1909)

of the South-West, the Handbook of the 1907 Annual Meeting of the British Medical Association.f The Scilly Islands alone were omciitted as, I understand, special arrangemiients are miade there for the emigration of the surplus population.
Childless women revisited. South Bedfordshire Practitioners' Group.
Authors: G Johnson
Journal: BMJ (1993)

life expectancy. 1-3Some reports have included data from north east England.5To our knowledge, however, no previous reports have assessed illness in diabetic patients in relation to social deprivation.In conclusion, we advocate three courses of action: firstly, to support the alleviation of social and economic disadvantage; secondly, to offer an excellent service to our patients with diabetes, aiming at optimal glycaemic control in order to minimise the risk of complications; and, thirdly, to continue to persuade patients not to smoke.We thank Middlesbrough Inner City
<i>Salmonella</i> Exploits Caspase-1 to Colonize Peyer's Patches in a Murine Typhoid Model
Authors: Denise M. Monack, David Hersh, Nafisa Ghori, Donna Bouley, Arturo Zychlinsky, Stanley Falkow
Journal: The Journal of Experimental Medicine (2000)

Salmonella typhimurium invades host macrophages and induces apoptosis and the release of mature proinflammatory cytokines. SipB, a protein translocated by Salmonella into the cytoplasm of macrophages, is required for activation of Caspase-1 (Casp-1, an interleukin [IL]-1β–converting enzyme), which is a member of a family of cysteine proteases that induce apoptosis in mammalian cells. Casp-1 is unique among caspases because it also directly cleaves the proinflammatory cytokines IL-1β and IL-18 to produce bioactive cytokines. We show here that mice lacking Casp-1 (casp-1−/− mice) had an oral S. typhimurium 50% lethal dose (LD50) that was 1,000-fold higher than that of wild-type mice. Salmonella breached the M cell barrier of casp-1−/− mice efficiently; however, there was a decrease in the number of apoptotic cells, intracellular bacteria, and the recruitment of polymorphonuclear lymphocytes in the Peyer's patches (PP) as compared with wild-type mice. Furthermore, Salmonella did not disseminate systemically in the majority of casp-1−/− mice, as demonstrated by significantly less colonization in the PP, mesenteric lymph nodes, and spleens of casp-1−/− mice after an oral dose of S. typhimurium that was 100-fold higher than the LD50. The increased resistance in casp-1−/− animals appears specific for Salmonella infection since these mice were susceptible to colonization by another enteric pathogen, Yersinia pseudotuberculosis, which normally invades the PP. These results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice.