tbuckley/cabot-search huggingface dataset:
The “Fetal Origins” Hypothesis: Challenges and Opportunities for Maternal and Child Nutrition
Authors: Kathleen Maher Rasmussen
Journal: Annual Review of Nutrition (2001)

▪ Abstract The “fetal origins” hypothesis postulates that conditions, most likely nutritional, “program” the fetus for the development of chronic diseases in adulthood. Associations between the newborn's size at birth and various determinants or consequences of chronic diseases have been identified in many, but not all, of the available studies. It remains to be established whether these associations are causal. Remarkably little information is available on the specific role of maternal nutritional status. The role of birth weight remains difficult to interpret except as a proxy for events in intrauterine life. Unfortunately, birth weight does not make an important contribution to the population attributable risk of cardiovascular disease; lifestyle factors during adulthood make much greater contributions. Data from experimental species suggest possible mechanisms for the origin of chronic disease early in life. It is too soon to use this research as a basis for new interventions directed at pregnant women for the purpose of reducing chronic disease in their offspring.
(6) Case for diagnosis. (?)Pyodermite vegetante of Hallopeau
Authors: C. Long
Journal: British Journal of Dermatology (1973)

Journal Article (6) Case for diagnosis. (?)Pyodermite végétante of Hallopeau Get access C. Long C. Long Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 39–40, https://doi.org/10.1111/j.1365-2133.1973.tb03439.x Published: 01 July 1973
Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm
Authors: Hiroaki Shimokawa, Minoru Seto, Naoki Katsumata, Mutsuki Amano, Toshiyuki Kozai, Tohru Yamawaki, Kouichi Kuwata, Tadashi Kandabashi, Kensuke Egashira, Ichiro Ikegaki, Toshio Asano, Kozo Kaibuchi, Akira Takeshita
Journal: Cardiovascular Research (1999)

Objective:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono-and diphosphorylations) play a central role in the pathogenesis of the spasm.However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC phosphorylations were unknown.In the present study, we addressed these points using hydroxyfasudil, a novel inhibitor of protein kinases, which we found preferentially inhibits Rho-kinase.Methods: The specificity of the inhibitory effects of hydroxyfasudil on Rho-kinase, MLCK, MRCKb and PKC were examined by kinase assay in vitro.The left porcine coronary artery was chronically treated with interleukin-1b (IL-1b, 2.5 mg).Two weeks after the operation, coronary artery vasomotion was examined both in vivo and in vitro.MLC phosphorylations were examined by Western blot analysis and the sites for the phosphorylations by anti-phosphorylated MLC antibodies that identified the monophosphorylation site as Ser19 and diphophorylation sites as Ser19 / Thr18 of MLC.Results: Inhibitory effects of hydroxyfasudil was at least 100 times more potent for Rho-kinase as compared with other protein kinases tested.Intracoronary serotonin (10 mg / kg) caused coronary hyperconstriction at the IL-1b-treated site in vivo, which was dose-dependently inhibited by hydroxyfasudil ( p,0.01).The coronary segment taken from the spastic site also showed hypercontractions to serotonin in vitro, which were again dose-dependently inhibited by hydroxyfasudil ( p,0.01).Western blot analysis showed that MLC monophosphorylation was significantly greater in the spastic segment than in the control segment, while MLC diphosphorylation was noted only at the spastic segment ( p,0.01).The sites for the mono-and diphosphorylated MLC were identified as the monophosphorylated site Ser19 and diphosphorylated sites Ser19 / Thr18 of MLC, respectively.Both types of MLC phosphorylations at the spastic segment were markedly inhibited by hydroxyfasudil ( p,0.01).Conclusion: These results indicate that hydroxyfasudilsensitive Rho-kinase-mediated pathway appears to mediate the enhanced MLC phosphorylations (on Ser19 and Ser19 / Thr18 residues) and plays a central role in the pathogenesis of coronary artery spasm.
Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases.
Authors: E Levy, C Lopez-Otin, J Ghiso, D Geltner, B Frangione
Journal: The Journal of Experimental Medicine (1989)

Cystatin C is an inhibitor of lysosomal cysteine proteases and consists of 120 amino acids. A variant of cystatin C lacking the first NH2-terminal residues and having one amino acid substitution at position 68 forms amyloid deposits mainly in the walls of brain arteries, causing fatal strokes in Icelandic patients with familial cerebral hemorrhage secondary to a form of an autosomal dominant amyloidosis. To understand the molecular basis of the genetic defect, the gene encoding cystatin C was isolated from genomic DNA libraries made from normal tissue and the brain of an Icelandic patient with hereditary cerebral hemorrhage with amyloidosis (HCHWA-I). The data indicate that the cystatin C gene encodes a polypeptide of 146 amino acids, of which the first 26 correspond to a secretory peptide signal sequence. The gene contains two intervening sequences that interrupt the coding region at amino acids 55 and 93. Comparison with genes encoding salivary cystatins and kininogen proteins show sequence homology and conservation of exon-intron structure. Except for a mutation in the second exon (CAG instead of CTG in the normal gene, resulting in the substitution of glutamine for a leucine residue), the gene cloned from the brain of the Icelandic patient is identical to the normal cystatin C gene. Thus, HCHWA-I is the first familial type of amyloidosis related to a point mutation in a gene encoding for an inhibitor. The mutation in the structural gene encoding cystatin C appears to be the primary defect in this inherited disorder causing amyloid fibril formation and accumulation followed by cerebral hemorrhage.
Prognostic affect of the chronic obstructive pulmonary disease on the local-advanced stage non-small cell lung cancer
Authors: Fatma Yildirim, Murat Türk, Ahmet Selim Yurdakul, Can Öztürk
Journal: European Respiratory Journal (2014)

Aim:In this study,we aimed to investigate the association of chronic obstructive pulmonary disease (COPD) with locally-advanced stage non-small cell lung cancer (NSCLC) in term of frequency, gender distribution, tumor histology, and its effect on the survival of patients.  Materials and Methods:Files of 350 patients with stage III and IV NSCLC were retrospectively analyzed. Patient demographic characteristics, smoking habits, ECOG status, time of diagnosis, TNM stage, tumor histological types, pulmonary function test (PFT) values, presence of COPD, treatment and survival of them were recorded.  Results:Total 137 patients with the mean age of 63 ± 10 were included. 118 (86.1%) of them were male, 19 (13.9%) were female. 20 (14.6%) patients had stage IIIA, 27 (19.7%) had stage IIIB, 90 (65.7%) had stage IV. Sixty-one (44.6%) patients had COPD at the time of diagnosis. There was no difference between groups with COPD and without COPD in terms of age, gender, tumor histology and treatment modalities (p>0.05). The amount of smoking was higher in the COPD group (p=0.028). There was no difference between the groups with COPD nad without COPD in terms of survival that was investigated with Kaplan-meier curves and log-rank test (p=0.445). When it was evaluated with logistic regression analysis, the presence of distant metastase was detected as a factor affecting the prognosis (p=0.008), but the presence of COPD was not significant factor affecting the prognosis (p=0.543).  Conclusion:In patients with locally-advanced NSCLC, the presence of COPD hasn9t been identified as a factor affecting the prognosis of patients.
Low‐dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit
Authors: Erik Lipšic, B. Daan Westenbrink, Peter van der Meer, Pim van der Harst, Adriaan A. Voors, Dirk J. van Veldhuisen, Regien G. Schoemaker, Wiek H. van Gilst
Journal: European Journal of Heart Failure (2008)
LOCALIZATION OF ANTIGEN IN TISSUE CELLS
Authors: Albert H. Coons, Melvin H. Kaplan
Journal: The Journal of Experimental Medicine (1950)

Improvements in a method for the specific microscopic localization of antigen in tissue cells are described. This method employs antibody labelled with fluorescein isocyanate as a histochemical stain, the specific antigen-antibody precipitate being made visible under the fluorescence microscope. Two isomeric series derived from nitrofluorescein are described.
Role of Burkholderia pseudomallei biofilm formation and lipopolysaccharide in relapse of melioidosis
Authors: D. Limmathurotsakul, A. Paeyao, S. Wongratanacheewin, N. Saiprom, N. Takpho, J. Thaipadungpanit, N. Chantratita, V. Wuthiekanun, N.P.J. Day, S.J. Peacock
Journal: Clinical Microbiology and Infection (2014)

We examined whether quantitative biofilm formation and/or lipopolysaccharide type of Burkholderia pseudomallei was associated with relapsing melioidosis. We devised a 1:4 nested case-control study in which both cases and controls were drawn from a cohort of patients with primary melioidosis. Paired isolates from 80 patients with relapse and single isolates from 184 patients without relapse were tested. Relapse was associated with biofilm formation of the primary infecting isolate (conditional OR 2.03; 95% CI 1.27-3.25; p 0.003), but not with lipopolysaccharide type (p 0.74). This finding highlights the importance of biofilm formation in relapsing melioidosis.
Mode of dialysis therapy and mortality in end-stage renal disease.
Authors: R N Foley, P S Parfrey, J D Harnett, G M Kent, R O'Dea, D C Murray, P E Barre
Journal: Journal of the American Society of Nephrology (1998)

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo. After adjustment for PD patients less likely to have chronic hypertension and more likely to have diabetes, ischemic heart disease, and cardiac failure at baseline (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there was no statistically significant difference in mortality. After 2 yr, mortality was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95% confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated with mortality after 2 yr. Progressive clinical and echocardiographic cardiac disease were not responsible for this late mortality. Lower mean serum albumin levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/- 0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in subsequent mortality. Hemodialysis has a late survival advantage over peritoneal dialysis; antecedent hypoalbuminemia is a major marker of the increased late mortality in PD patients.
In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development
Authors: M. Goto
Journal: Journal of Clinical Investigation (2006)

In humans, sexual differentiation of the external genitalia is established at 7-12 weeks post conception (wpc). During this period, maintaining the appropriate intrauterine hormone environment is critical. In contrast to other species, this regulation extends to the human fetal adrenal cortex, as evidenced by the virilization that is associated with various forms of congenital adrenal hyperplasia. The mechanism underlying these clinical findings has remained elusive. Here we show that the human fetal adrenal cortex synthesized cortisol much earlier than previously documented, an effect associated with transient expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B) and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under the regulation of ACTH. Negative feedback was apparent at the anterior pituitary corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione and testosterone. In concert, these data promote a distinctive mechanism for normal human development whereby cortisol production, determined by transient NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to modulate androgen biosynthesis and safeguard normal female sexual differentiation.
Management of bleeding oesophageal varices by draining lymph from the thoracic duct
Authors: D. V. Datta, S. A. K. Singh, B. S. Patra, V. K. Saini, P. N. Chhuttani
Journal: Gut (1971)

The thoracic duct was cannulated in six patients who were actively bleeding from varices and had not responded to conservative treatment but draining lymph from the thoracic duct did not control bleeding in five patients. There was no drop in intrasplenic pulp pressure following this procedure when recorded in three of these patients. Bleeding stopped in one patient after lymph had been drained for nine and a half hours, and there was only a modest change in intrasplenic pressure. The therapeutic use of this technique to control oesophageal varices could not be substantiated.
P<scp>ROTEIN AND</scp> A<scp>MINO</scp> A<scp>CID</scp> M<scp>ETABOLISM</scp> D<scp>URING AND</scp> A<scp>FTER</scp> E<scp>XERCISE AND THE</scp> E<scp>FFECTS OF</scp> N<scp>UTRITION</scp>
Authors: Michael J. Rennie, Kevin D. Tipton
Journal: Annual Review of Nutrition (2000)

▪ Abstract Sustained dynamic exercise stimulates amino acid oxidation, chiefly of the branched-chain amino acids, and ammonia production in proportion to exercise intensity; if the exercise is intense enough, there is a net loss of muscle protein (as a result of decreased protein synthesis, increased breakdown, or both); some of the amino acids are oxidized as fuel, whereas the rest provide substrates for gluconeogenesis and possibly for acid-based regulation. Protein balance is restored after exercise, but no hypertrophy occurs with habitual dynamic exercise. Resistance exercise causes little change in amino acid oxidation but probably depresses protein synthesis and elevates breakdown acutely. After exercise, protein synthesis rebounds for ≤48 h, but breakdown remains elevated, and net positive balance is achieved only if amino acid availability is increased. There is no evidence that habitual exercise increases protein requirements; indeed protein metabolism may become more efficient as a result of training.
Risk of Mortality Among Individual Antipsychotics in Patients With Dementia
Authors: Helen C. Kales, Hyungjin Myra Kim, Kara Zivin, Marcia Valenstein, Lisa S. Seyfried, Claire Chiang, Francesca Cunningham, Lon S. Schneider, Frederic C. Blow
Journal: American Journal of Psychiatry (2011)

Haloperidol had 1.5 times the risk of mortality of other psychotropics in patients with dementia studied in an outpatient VA setting. Risperidone, valproic acid and derivatives, and olanzapine had intermediate risk, and quetiapine had the lowest risk. Haloperidol was more frequently prescribed by nonpsychiatrists and more often in older, medically ill African Americans. Quetiapine was prescribed in lower doses, often for less ill patients, but was associated with increased parkinsonian symptoms. The increased risk of haloperidol was primarily in the first 30 days. The efficacy of quetiapine in the behavioral disturbances associated with dementia is questionable, whereas risperidone and olanzapine have significant beneficial effects and therefore would be preferred for treatment.
TREATMENT OF HYPERKINETIC EMOTIONALLY DISTURBED CHILDREN WITH PROLONGED ADMINISTRATION OF CHLORPROMAZINE
Authors: HERBERT FREED, CHARLES A. PEIFER
Journal: American Journal of Psychiatry (1956)

Twenty-five hyperkinetic, emotionally disturbed children were treated with chlorpromazine for periods lasting from 4 to 16 months. They also served as their own controls by receiving placebo medication for 4 to 6 weeks during some phase of treatment. Response was determined from the following observations: (1) Clinical changes noted by the clinic staff which included the social worker and psychologist as well as the therapist; (2) data from the home environment; (3) reports from the school counselors; (4) changes in the battery of psychological tests done before and after treatment. Improvement in varying degrees was noted in 21 cases—84%, and was marked in 70%. Diminution in hyperactivity was the outstanding phenomenon. Combativeness was reduced considerably. There was definite improvement in willingness to learn. The psychological testing suggested that the learning process was facilitated. Trends toward increased emotional control were evidenced although the basic personality seemed unchanged. The procedure was effective because an "improved interpersonal relationship" could be established and exploited for the sake of the learning process. The side effects were minimal compared with those of adults and did not necessitate the termination of treatment in any case. Sequential blood count studies were negative. It is suggested that, perhaps for the first time, we have a drug which dampens the primitive fight-flight responses, possibly actuated by the "arousal system" of Magoun (15). It is further suggested that by controlling this basic mechanism without impairing consciousness and the learning process, we can now do more effective psychotherapy. We seem to have entered the era of "combined therapy" where drug therapy and psychotherapy are complementary and can be combined to change the personality most effectively.
Phase III Trial Comparing Doxorubicin Plus Cyclophosphamide With Docetaxel Plus Cyclophosphamide As Adjuvant Therapy for Operable Breast Cancer
Authors: Stephen E. Jones, Michael A. Savin, Frankie Ann Holmes, Joyce A. O'Shaughnessy, Joanne L. Blum, Svetislava Vukelja, Kristi J. McIntyre, John E. Pippen, James H. Bordelon, Robert Kirby, John Sandbach, William J. Hyman, Pankaj Khandelwal, Angel G. Negron, Donald A. Richards, Stephen P. Anthony, Robert G. Mennel, Kristi A. Boehm, Walter G. Meyer, Lina Asmar
Journal: Journal of Clinical Oncology (2006)

The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS).Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy.Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure.At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.
Does having previous sputum results improve rationalisation of antimicrobial prescribing during acute exacerbations of COPD
Authors: Rebecca Dickinson, Jamie Talbot, Joanne Thompson, Helena Cummings, Jaymin Morjaria
Journal: European Respiratory Journal (2014)

Background  Patients presenting with acute exacerbations of COPD (AECOPD) are regularly prescribed antibiotic therapy. Previous sputum microbiological cultures are a useful guide to tailoring antibiotic therapy. To reduce antibiotic resistance there is a push towards using narrow spectrum antibiotic therapy (AT). We examined whether local antibiotic prescribing was in concordance with known sputum microbiology or guidelines.  Methods  We reviewed two months of AECOPD admissions to our tertiary hospital. Previous sputum microbiology (4 weeks to 5 years) and index admission AT data was collected. Appropriate AT was defined as narrow spectrum antibiotics given according to previous sputum culture or according to hospital guidelines for AECOPD if no previous or a previous negative sputum or pneumonia if diagnosed.  Results  117 patients with a mean ages of 72.5 years (58M: 59F), out of 159 admissions, were reviewed. Table 1 summaries AT and concordance with previous sputum microbiology.  Sixteen (53%) patients with no previous sputum results were given broad spectrum antibiotics.  Conclusion  Many patients were inappropriately prescribed broad spectrum antibiotics without consideration of previous sputum microbiology or hospital guidelines. Education of medical staff is extremely important to improve concordance and reduce inappropriate AT.
Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail
Authors: Ronald C. Savin, Lynn Drake, Dennis Babel, Daniel M. Stewart, Phoebe Rich, Mark R. Ling, Debra Breneman, Richard K. Scher, Ann G. Martin, David M. Pariser, Robert J. Pariser, Charles N. Ellis, Sewon Kang, David Friedman, Harry Irving Katz, Charles J. McDonald, Jennie Muglia, Guy Webster, Boni E. Elewski, James J. Leyden, Alicia D. Bucko, Eduardo H. Tschen, Jon M. Hanifin, Manuel R. Morman, Jerome L. Shupack, Norman Levine, Nicholas J. Lowe, Wilma F. Bergfeld, Charles Camisa, David Stuart Feingold, Nellie Konnikov, Richard B. Odom, Raza Aly, Donald L. Greer, James Hilbert
Journal: Journal of the American Academy of Dermatology (1998)