tbuckley/cabot-search huggingface dataset:
Treatment of Cognitive Impairment in Early Psychosis: A Comparison of Risperidone and Haloperidol in a Large Long-Term Trial
Authors: Philip D. Harvey, Jonathan Rabinowitz, Marielle Eerdekens, Michael Davidson
Journal: American Journal of Psychiatry (2005)

Cognitive impairment is a major determinant of functional outcome in schizophrenia. Treatment of cognitive impairment at the time of the first episode may have the potential to change functional outcomes of the illness. This study examined changes associated with treatment with risperidone compared with haloperidol in aspects of cognitive functioning known to be associated with functional outcomes. The study was conducted in a large group of patients experiencing their first episode of schizophrenia.Cognitive assessments were conducted in 533 patients experiencing their first episode of schizophrenia or a related psychosis who had been randomly assigned to receive low doses of risperidone or haloperidol. The cognitive assessments were repeated at several different follow-up intervals; 359 patients were reexamined at the 3-month follow-up. The assessments included examinations of verbal and visuospatial episodic memory, vigilance, executive functioning, processing speed, and verbal fluency. Patients' clinical symptoms were also rated with the Positive and Negative Syndrome Scale.Improvements from baseline were found in the risperidone-treated patients for episodic memory, verbal fluency, vigilance, executive functioning, and visuomotor speed. Haloperidol-treated patients also showed improvements from baseline in episodic memory, vigilance, and visuomotor speed but not in executive functioning or verbal fluency. Comparison of differential treatment effects on a composite measure of cognitive functioning found that risperidone was significantly more beneficial than haloperidol after 3 months of treatment. Changes in Positive and Negative Syndrome Scale scores were correlated overall with improvement in the haloperidol-treated patients but not in the risperidone-treated patients.Treatment with risperidone at the time of the first episode of schizophrenia is associated with wide-ranging improvements in cognitive functioning. Overall improvement is significantly greater with risperidone than with haloperidol. Further, cognitive improvement associated with treatment with risperidone was not influenced by changes in symptoms, but that relationship was significant in haloperidol-treated patients.
Ciguatera Fish Poisoning
Authors: J. Glenn Morris
Journal: JAMA (1980)

Ciguatera fish poisoning, with its characteristic gastrointestinal and neurological symptoms, has been clearly described in literature from the West Indies since the 18th century, with fragmentary reports dating back to the 1500s.<sup>1</sup>It is currently a major cause of morbidity in the Caribbean,<sup>2</sup>as well as in the South Pacific, where Bagnis and his colleagues<sup>3</sup>have recently reported on a series of more than 3,000 cases. In the United States 94 outbreaks (418 cases) have been reported to the Center for Disease Control (CDC) through the national foodborne disease surveillance system since 1970, making ciguatera the most frequently reported foodborne disease associated with consumption of seafood; outbreaks have occurred most frequently in southeastern Florida and Hawaii, with sporadic cases, usually associated with a history of travel to the Caribbean, reported from other parts of the country. The CDC data undoubtedly represent substantial underreporting of the disease, however.
Outcome determinants for transformed indolent lymphomas treated with or without autologous stem-cell transplantation
Authors: C. Madsen, M.B. Pedersen, M.Ø. Vase, K. Bendix, M.B. Møller, P. Johansen, B.A. Jensen, P. Jensen, L. Munksgaard, P.D. Brown, E.K. Segel, F.A. d'Amore
Journal: Annals of Oncology (2014)

Transformation of indolent lymphomas (IL) to an aggressive histology (TIL) often results in a rapid clinical course, treatment refractoriness and shortened survival. Although rituximab-containing regimens (R-chemo) have become standard of care in CD20-positive TIL, the role of autologous stem-cell transplantation (ASCT) is still debated. The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high-grade components diagnosed either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab treatment during the indolent course of the disease affected outcome after transformation.Eighty-five patients (≤68 years) with histologically confirmed TIL were included. Five-year overall (OS) and progression-free survival (PFS) were calculated. Selected parameters were tested in a multivariate analysis. All analyses were conducted on three cohorts: (i) whole cohort (all TIL), (ii) patients with co-existing evidence of both indolent and aggressive histology at diagnosis (Composite/discordant TIL) and (iii) patients transformed after prolonged prior indolent disease (sequential TIL).Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the 'all TIL' cohort, the 5-year OS and PFS for R-chemo + ASCT versus R-chemo alone, were 67% versus 48% (P = 0.11) and 60% versus 30% (P = 0.02), respectively. Furthermore, in 'Composite/discordant TIL' R-chemo + ASCT showed no impact on OS (76% versus 67%; P = 0.66) or PFS (71% versus 62%; P = 0.54). Conversely, R-chemo + ASCT improved the outcome of 'sequential TIL' (OS 62% versus 36%; P = 0.07; PFS 53% versus 6%; P = 0.002), regardless of prior rituximab therapy. The beneficial effect of ASCT was significantly higher in patients who had not received rituximab at IL stage.ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact of ASCT was greater in patients, who were rituximab-naïve at transformation.
Effect of a leukotriene B4 receptor antagonist SC-53228 on ozone-induced airway hyperresponsiveness and inflammation in dogs.
Authors: W H Stevens, C Vanderheyden, J Wattie, C G Lane, W Smith, P M O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The importance of the potent neutrophil chemoattractant leukotriene (LT)B4 in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs was studied using the LTB4-receptor antagonist SC-53228. Seven dogs from random sources were studied three times, at least 2 wk apart. On each occasion, acetylcholine (Ach) airway responsiveness was measured before and 1 h after ozone (3 ppm, 30 min) or dry air inhalation, followed by a bronchoalveolar lavage (BAL). On the first day, dogs were treated with SC-53228 (0.4 mg/kg intravenously) followed by a continuous intravenous infusion of 1.2 mg/kg/h before ozone inhalation. On the other two days, diluent was infused followed by ozone or dry air inhalation. Cell counts were measured in BAL and cell activation was measured by spontaneous and by phorbol myristate acetate-stimulated (PMA) (2.4 mumol/L) oxygen radical release, measured from washed BAL cells (4 x 10(6) cells) by lucigenin-enhanced chemiluminescence. Ozone inhalation caused bronchoconstriction and airway hyperresponsiveness. SC-53228 inhibited the ozone-induced airway hyperresponsiveness (p = 0.006), but not the bronchoconstriction. Spontaneous (p = 0.004) and PMA-stimulated (p = 0.04) lucigenin-enhanced chemiluminescence were increased after ozone inhalation. The ozone-induced increases in PMA-stimulated chemiluminescence were significantly attenuated by treatment with SC-53228 (p = 0.04). These results suggest that LTB4 is involved in the pathogenesis of ozone-induced airway hyperresponsiveness, possibly through activation of airway inflammatory cell.
Baroreflex Sensitivity and Its Response to Deep Breathing Predict Increase in Blood Pressure in Type 1 Diabetes in a 5-Year Follow-Up
Authors: Milla Rosengård-Bärlund, Luciano Bernardi, Anna Sandelin, Carol Forsblom, Per-Henrik Groop
Journal: Diabetes Care (2011)

OBJECTIVE We have recently demonstrated that early autonomic dysfunction, defined as low baroreflex sensitivity (BRS), could be functional and reversible. However, potential temporal changes in BRS have not yet been addressed by longitudinal studies in type 1 diabetes. Moreover, it is not known whether low BRS predisposes to hypertension or other nonfatal diabetes complications. RESEARCH DESIGN AND METHODS We conducted a 5-year prospective study including 80 patients with type 1 diabetes. We measured ambulatory blood pressure and autonomic function tests. BRS was assessed by six different methods during spontaneous, controlled, and slow deep breathing at baseline and follow-up. RESULTS Spontaneous BRS declined over time (BRSaverage 16.2 ± 0.8 vs. 13.2 ± 0.8 ms/mmHg; P &amp;lt; 0.01), but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not progress to cardiac autonomic neuropathy but predicted an increase in the nighttime systolic blood pressure (BRSaverage r = −0.37; P &amp;lt; 0.05). Additionally, BRS response to deep breathing at baseline predicted an increase in 24-h ambulatory blood pressure (BRS-αLF r = 0.323–0.346; P &amp;lt; 0.05). CONCLUSIONS The decline in spontaneous BRS over time in patients with type 1 diabetes seems to be due to normal aging, which supports a functional etiology behind early autonomic derangements. Decreased resting BRS and the magnitude of improvement by deep breathing may be due to sympathovagal imbalance, a well-known mechanism in the development of hypertension. Early interventions aiming to reduce sympathetic overactivity in patients with low BRS might delay the development of hypertension.
Doctors in Scotland must change working patterns, report says
Authors: B. Christie
Journal: BMJ (2002)

Changes are needed in the way doctors work if the ever rising demand for health care is to be met, a review of future medical workforce requirements in Scotland has concluded.

It says that more doctors will be needed in Scotland, but they will have to work differently. The report says that more effective partnership working is needed in primary care, together with a redesign of hospital services—including a separation of “cold units,” specialising in elective work, and “hot units,” handling acute and emergency cases. More integrated team working based on managed …
Adenosine regulates radiation therapy-induced anti-tumor immunity
Authors: Erik Wennerberg, Noriko Kawashima, Sandra Demaria
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Radiation therapy (RT) induces immunogenic cell death and dose-dependent release of ATP in the tumor microenvironment (TME), triggering maturation and activation of tumor-resident dendritic cells (DCs). However, extracellular ATP is rapidly catabolized to adenosine by
Magnitude of Response With Myeloma Frontline Therapy Does Not Predict Outcome: Importance of Time to Progression in Southwest Oncology Group Chemotherapy Trials
Authors: Brian G.M. Durie, Joth Jacobson, Bart Barlogie, John Crowley
Journal: Journal of Clinical Oncology (2004)

Four Southwest Oncology Group (SWOG) standard-dose chemotherapy protocols for multiple myeloma (MM) initiated between 1982 and 1992 were evaluated. The purpose was to clarify the predictive value of specific levels of myeloma-associated monoclonal protein reduction and time to first progression using mature data sets.Study data on 1,555 eligible previously untreated patients with MM enrolled onto SWOG phase III trials 8229, 8624, 9028, and 9210 were used in these analyses. Six-month and 12-month landmark analyses were performed to evaluate the outcome for patients in each response category.The overall and event-free survivals for the four protocols combined were 33 months and 18 months, respectively. Using 6- and 12-month landmarks, the median survivals of 30 to 35 months were not different for responders (> or = 50% and > or = 75% regression) versus nonresponders in patients without disease progression before the landmarks. Conversely, at the 6- and 12-month landmarks, the median survivals for patients who had experienced disease progression were 13 and 15 months, respectively, versus a 34-month median for patients who did not experience progression. Using the Cox survival model, with response and progression considered as time-dependent covariates, survival duration was influenced more by the occurrence of progression than by the occurrence of response.The magnitude of response, as a single variable, does not predict survival duration. Patients with response and stable disease have equivalent outcome. Only patients with progressive disease have a poorer outcome. The best indicator of survival is time to first progression.
Dephosphorylation of autoantigenic ribosomal P proteins during Fas-L induced apoptosis: a possible trigger for the development of the autoimmune response in patients with systemic lupus erythematosus
Authors: S Zampieri
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> Autoimmune diseases are characterised by the production of autoantibodies against various autoantigens. In the past few years data have been published on a possible role of apoptosis in the development of autoimmunity. These include the finding that several autoantigens become modified (for example, by cleavage) during apoptosis, and the observation that these modified antigens are translocated to the cell surface. When the normal clearance of apoptotic cells somehow is disturbed, such modified antigens might become exposed to the immune system. Because acidic ribosomal P (phospho-) proteins targeted by autoantibodies in systemic lupus erythematosus (SLE) are also concentrated at the surface of apoptotic cells, this study aimed at investigating what modifications occur on these antigens during apoptosis. <h3>METHODS</h3> Apoptosis in Jurkat cells was induced by Fas ligand (Fas-L), and the fate of autoantigenic P proteins was analysed in both normal and apoptotic total cell extracts. <h3>RESULTS</h3> The autoantigenic P proteins were not cleaved but dephosphorylated during Fas-L induced apoptosis. This dephosphorylation was prevented when caspase activity was inhibited. <h3>CONCLUSIONS</h3> As has been shown for other autoantigens targeted by autoantibodies in SLE, P proteins also are modified during apoptosis. P1 and P2 are completely dephosphorylated while P0 is partly dephosphorylated. Because the epitope targeted by autoantibodies normally is phosphorylated, it is possible that the apoptotic dephosphorylation of the antigen might be the trigger for the development of the autoimmune response against P proteins.
Heme Oxygenase-2 Deficiency Contributes to Diabetes-Mediated Increase in Superoxide Anion and Renal Dysfunction
Authors: Alvin I Goodman, Praveen N Chander, Rita Rezzani, Michal L Schwartzman, Raymond F Regan, Luigi Rodella, Saadet Turkseven, Elias A Lianos, Phyllis A Dennery, Nader G Abraham
Journal: Journal of the American Society of Nephrology (2006)

Heme oxygenase-1 (HO-1) and -2 play an important role in cytoprotection and are physiologic regulators of heme-dependent protein synthesis in renal tissues. The impact of HO-2 deletion comparing hyperglycemic HO-2 (+/+) mice and HO-2 knockout (-/-) mice was examined. Hyperglycemia was induced by streptozotocin (STZ) injection, and its effect on renal HO-1/HO-2 protein, HO activity, and creatinine levels were assessed. The effect of HO induction using systemic administration of the HO inducers heme or cobalt protoporphyrin and the effect of HO inhibition using systemic administration of the HO inhibitor tin mesoporphyrin also were assessed in STZ-treated mice. In STZ-treated HO-2 (-/-) mice, there was marked renal functional impairment as reflected by an increase in plasma creatinine, associated with acute tubular damage and microvascular pathology as compared with HO-2 (+/+). In these animals, HO activity was decreased with a concomitant increase in superoxide anion. Upregulation of HO-1 in HO-2 (-/-) mice by weekly administration of cobalt protoporphyrin prevented the increase in plasma creatinine levels and tubulointerstitial and microvascular pathology. Inhibition of HO activity by administration of tin mesoporphyrin accentuated superoxide production and increased creatinine levels in hyperglycemic HO-2 (-/-) mice. In conclusion, HO-2 deficiency enhanced STZ-induced renal dysfunction and morphologic injury and HO-1 upregulation in HO-2 (-/-) mouse rescue and prevented the morphologic damage. These observations indicate that HO activity is essential in preserving renal function and morphology in STZ-induced diabetic mice probably via mitigation of concomitant oxidative stress.
Diabetes and the Risk of Developing Parkinson’s Disease in Denmark
Authors: Eva Schernhammer, Johnni Hansen, Kathrine Rugbjerg, Lene Wermuth, Beate Ritz
Journal: Diabetes Care (2011)

OBJECTIVE Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson’s disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson’s disease. RESEARCH DESIGN AND METHODS From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of Parkinson’s disease between 2001 and 2006. We randomly selected 9,651 population control subjects from the Central Population Registry and density matched them by birth year and sex. Pharmacy records comprising all antidiabetes and anti-Parkinson drug prescriptions in Denmark were available. Odds ratios (ORs) were estimated by logistic regression models. RESULTS Having diabetes, as defined by one or more hospitalizations and/or outpatient visits for the condition, was associated with a 36% increased risk of developing Parkinson’s disease (OR 1.36 [95% CI 1.08–1.71]). Similarly, diabetes defined by the use of any antidiabetes medications was associated with a 35% increased Parkinson’s disease risk (1.35 [1.10–1.65]). When diabetes was defined as the use of oral antidiabetes medications, effect estimates were stronger in women (2.92 [1.34–6.36]), whereas when diabetes was defined as any antidiabetes drug prescription, patients with early-onset Parkinson’s disease were at highest risk (i.e., Parkinson’s disease diagnosed before the age of 60 years; 3.07 [1.65–5.70]). CONCLUSIONS We found that a diagnosis of, or treatment received for, diabetes was significantly associated with an increased risk of developing Parkinson’s disease, especially younger-onset Parkinson’s disease. Our results suggest a common pathophysiologic pathway between the two diseases. Future studies should take age at Parkinson’s disease onset into account.
Ampicillin-Probenecid Treatment of Gonorrhea
Authors: Mary Riggs
Journal: JAMA (1972)

To the Editor.—  In connection with the continuing search for an efficient and safe treatment for gonorrhea (Neumann and Baecker, Treatment of Gonorrhea, 219 :471-474,1972), I wish to report briefly on our experience with single dose, combined, oral ampicillin administration and probenecid in the therapy of uncomplicated gonococcal infection. The use of this treatment schedule has previously been reported by Holmes and associates for both male 1 and female 2 patients, but in both series the probenecid was administered one hour prior to ampicillin, in a well defined, limited population. In a crowded public clinic the one-hour wait is undesirable; but the high success rate and lack of side effects are advantageous.  We are using ampicillin, 3.5 gm, and probenecid, 1 gm, administered orally together to treat both male and female gonorrhea patients. In the series reported here, diagnosis was established by gram-stained smears or cultures in males and by
Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters
Authors: Eriko Kikuchi, Takayasu Mori, Moko Zeniya, Kiyoshi Isobe, Mari Ishigami-Yuasa, Shinya Fujii, Hiroyuki Kagechika, Tomoaki Ishihara, Tohru Mizushima, Sei Sasaki, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Journal: Journal of the American Society of Nephrology (2014)

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na+-Cl− cotransporter (NCC) and Na+-K+-2Cl− cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.
PENTAQUINE (SN-13,276), A THERAPEUTIC AGENT EFFECTIVE IN REDUCING THE RELAPSE RATE IN VIV AX MALARIA 1
Authors: Alf S. Alving, Branch Craige, Ralph Jones, C. Merrill Whorton, Theodore N. Pullman, Lillian Eichelberger
Journal: Journal of Clinical Investigation (1948)

the former group bred Anopheles quadrimaculatus mosquitoes, supervised their infection and the inoculation of volunteers, and determined the intensity of infection in the salivary glands of the mosquitoes.The latter group assumed the responsibility for clinical care of patients studied by both groups.
Alcoholic liver injury: Defenestration in noncirrhotic livers—a scanning electron microscopic study
Authors: Thomas Horn, Per Christoffersen, Jens H. Henriksen
Journal: Hepatology (1987)

The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall (fractional area of fenestrae) was observed in acinar Zone 3, both in biopsies with and without Zone 3 fibrosis as judged by light microscopy. A significant reduction of porosity as shown in this study may influence the blood hepatocytic exchange and contribute to the alcohol-induced liver injury.