tbuckley/cabot-search huggingface dataset:
Relapse Prevention in Schizophrenia With New-Generation Antipsychotics: A Systematic Review and Exploratory Meta-Analysis of Randomized, Controlled Trials
Authors: Stefan Leucht, Thomas R.E. Barnes, Werner Kissling, Rolf R. Engel, Christoph Correll, John M. Kane
Journal: American Journal of Psychiatry (2003)

The authors performed a systematic review and meta-analysis of studies of the potential of new-generation antipsychotic drugs to improve adherence and decrease relapse rates in patients with schizophrenia.Randomized, controlled trials comparing new-generation antipsychotic drugs with placebo and/or conventional antipsychotics were identified. Data on relapse, general treatment failure, and dropout due to adverse events were extracted and combined in a meta-analysis.Because few trials were available for each individual drug, the effects of new-generation antipsychotic drugs as a group were analyzed. The analysis of six placebo comparisons, involving a total of 983 patients, clearly demonstrated that new-generation antipsychotic drugs are effective for relapse prevention. Eleven studies with a total of 2,032 patients provided comparative data on relapse/treatment failure for new-generation and conventional antipsychotics. The analysis revealed that rates of relapse and overall treatment failure were modestly but significantly lower with the newer drugs. Whether this advantage was partly mediated by improved adherence to treatment remains unclear. No significant superiority in terms of fewer dropouts due to adverse events was found for the newer drugs. Furthermore, a number of methodological problems were identified.Overall, the currently available data suggest that new-generation antipsychotics have the potential to reduce relapse rates. Methodological issues to be addressed in future trials include the choice of comparator, use of appropriate doses, application of clinically relevant relapse criteria, monitoring of adherence, and minimization of dropouts.
Prospective Randomized Study of the Effect of “Add-Back” Hormone Replacement on Vascular Function During Treatment With Gonadotropin-Releasing Hormone Agonists
Authors: S.F. Yim, T.K. Lau, D.S. Sahota, T.K.H. Chung, A.M.Z. Chang, C.J. Haines
Journal: Circulation (1998)

Background —Gonadotropin-releasing hormone agonists (GnRHas) are a group of drugs that with long-term use induce a pseudomenopausal state in which estrogen production is suppressed. They are commonly used in the treatment of sex steroid–dependent conditions. “Add-back” hormone replacement therapy is used to prevent menopause-like symptoms and bone loss during GnRHa treatment, but it is also recognized that hypoestrogenism adversely affects vascular function. The aim of this study was to examine the effect of GnRHa and add-back therapy on vascular reactivity. This model serves as a paradigm for the effect of hormone replacement therapy in postmenopausal women. Methods and Results —Measurements of endothelium-dependent and endothelium-independent vascular reactivity were compared in 2 groups of women treated with a GnRHa for 6 months. One group received estrogen/progestogen add-back therapy during the second 3 months of GnRHa treatment. Vascular reactivity was examined by use of ultrasound measurements of changes in brachial artery diameter. Endothelium-dependent changes were assessed during reactive hyperemia, whereas endothelium-independent changes were measured after the administration of glyceryl trinitrate sublingual spray. Treatment with the GnRHa alone had an inhibitory effect on endothelium-dependent relaxation. However, endothelium-dependent relaxation significantly improved in the group receiving add-back therapy (14.6%) compared with the group treated with GnRHa alone (8.6%) ( P &lt;0.01). There were no significant endothelium-independent changes in either group. Conclusions —These results suggest that the administration of add-back therapy has a protective effect on vascular function in GnRHa-induced hypoestrogenism. As a model for the menopause, these results also suggest that the long-term administration of hormone replacement therapy would result in endothelium-dependent arterial relaxation, an observation previously attributed only to the acute administration of estrogen.
Pharmacokinetics of alphaIFN-2b in chronic hepatitis C virus patients undergoing chronic hemodialysis or with normal renal function
Authors: L Rostaing, E Chatelut, J L Payen, J Izopet, C Thalamas, H Ton-That, J P Pascal, D Durand, P Canal
Journal: Journal of the American Society of Nephrology (1998)

In this prospective controlled study, the pharmacokinetic profiles of alpha-interferon 2b (alphaIFN-2b) were determined by the enzyme-linked immunosorbent assay method in hepatitis C virus-positive (HCV+) dialysis and nonuremic patients, after a single subcutaneous injection of 3 million units. Ten HCV+/RNA+ patients (group A) with a normal renal function (mean serum creatinine: 1.03 +/- 0.26 [SD] mg/dl) and 10 HCV+/RNA+ patients undergoing chronic hemodialysis (group B) were included. The pharmacokinetic profiles of alphaIFN were determined after the very first subcutaneous injection of the drug. Plasma alphaIFN concentrations were determined before the injection and then 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, and 36 h after the injection. They were assessed by means of an enzyme-linked immunosorbent assay test. Patients from both groups had a similar body surface area. It was found that in group B: (1) the mean maximum (SD) serum alphaIFN concentration (Cmax) was significantly higher (52 +/- 12 pg/ml) than in group A (39 +/- 12 pg/ml; P = 0.03); (2) the time at which Cmax occurred (Tmax) was significantly higher (10 +/- 3 h) than in group A (7.5 +/- 2 h; P = 0.05); (3) the observed area under the plasma alphaIFN concentration-time curve was about twice as much, i.e., 936 +/- 212 pg x h/ml, as that for group A (485 +/- 184 pg x h/ml; P < 0.0001); and (4) the alphaIFN half-life was significantly longer (9.6 +/- 2.9 h) than in group A (5.3 +/- 1.3 h). As early as 24 h after the alphaIFN injection was given, the drug was no longer detectable in nonuremic patients' sera, whereas it could be detected up to the next injection in all of the dialysis patients' sera. When trough levels of alphaIFN were measured just before the 10th injection, they were always below the threshold level in the 10 patients from group A, i.e., 4.1 pg/ml, whereas in group B they were measurable for four of nine patients (P = 0.05) and ranged between 5.8 and 36.1 pg/ml. Severe neurologic side effects were observed only in group B, i.e., in three patients. Hemoglobin levels did significantly decrease but only in group B patients, and this was significantly correlated with the Cmax (r = 0.67; P = 0.03). This is the first controlled study to demonstrate that the clearance of alphaIFN is about twice as low in dialysis patients as in nonuremic patients. These results might be of relevance when deciding the optimal alphaIFN therapy scheme for HCV+ patients, either with normal renal function or undergoing chronic hemodialysis.
The Production of Experimental Congestive Heart Failure in Rabbits
Authors: NATALIE ALEXANDER, HUGH A. EDMONDSON, DOUGLAS R. DRURY
Journal: Circulation Research (1953)

Observations were made on blood pressure, heart size, and physiologic state of 33 rabbits subjected to severe constriction of the abdominal aorta. Two-thirds of the rabbits developed symptoms of congestive heart failure and died within two weeks. Autopsy findings revealed acute passive congestion of liver and lungs in the majority of cases and chronic passive congestion of liver and heart failure cells in lungs in some animals which survived a month or more. Advantages of this method are simplicity of operative procedure and high incidence of heart failure.
Blood kinetics of Ebola virus in survivors and nonsurvivors
Authors: Simone Lanini, Gina Portella, Francesco Vairo, Gary P. Kobinger, Antonio Pesenti, Martin Langer, Soccoh Kabia, Giorgio Brogiato, Jackson Amone, Concetta Castilletti, Rossella Miccio, Alimuddin Zumla, Maria Rosaria Capobianchi, Antonino Di Caro, Gino Strada, Giuseppe Ippolito
Journal: Journal of Clinical Investigation (2015)

Infection with Ebola virus (EBOV) results in a life-threatening disease, with reported mortality rates between 50%-70%. The factors that determine patient survival are poorly understood; however, clinical observations indicate that EBOV viremia may be associated with fatal outcome. We conducted a study of the kinetics of Zaire EBOV viremia in patients with EBOV disease (EVD) who were managed at an Ebola Treatment Centre in Sierra Leone during the recent West African outbreak.Data from 84 EVD patients (38 survivors, 46 nonsurvivors) were analyzed, and EBOV viremia was quantified between 2 and 13 days after symptom onset. Time since symptom onset and clinical outcome were used as independent variables to compare EBOV viral kinetics in survivors and nonsurvivors.In all patients, EBOV viremia kinetics was a quadratic function of time; however, EBOV viremia was 0.94 logarithm (log) copies per ml (cp/ml) (P = 0.011) higher in nonsurvivors than in survivors from day 2 after the onset of symptoms. Survivors reached peak viremia levels at an earlier time after symptom onset than nonsurvivors (day 5 versus day 7) and had lower mean peak viremia levels compared with nonsurvivors (7.46 log cp/ml; 95% CI, 7.17-7.76 vs. 8.60 log cp/ml; 95% CI, 8.27-8.93). Before reaching peak values, EBOV viremia similarly increased both in survivors and nonsurvivors; however, the decay of viremia after the peak was much stronger in survivors than in nonsurvivors.Our results demonstrate that plasma concentrations of EBOV are markedly different between survivors and nonsurvivors at very early time points after symptom onset and may be predicative of outcome. Further studies focused on the early phase of the disease will be required to identify the causal and prognostic factors that determine patient outcome.Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY's private donations; and Royal Engineers for DFID-UK.
Press: When Jesica died
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

A teenager's death has highlighted medical errors and transplant problems in the United States

Sunday 16 March was a bad media day for American medicine—a really bad day, considering it came during annual Patient Safety Week.

The popular CBS investigative programme 60 Minutes broadcast “Anatomy of a Mistake,” detailing the simple error that killed transplant patient Jesica Santillan. The New York Times headlined its Sunday magazine “Half of what doctors know is wrong” and devoted the issue to “exploring medicine and its myths.”

Coming on the same day and reaching millions, these two events may be a watershed in focusing public attention on the related problems of medical errors, transplant mistakes, and the malpractice mess.

Just four days later, on 20 March, the New England Journal of Medicine published a damning Perspective article about the Jesica Santillan case entitled “A Death at Duke” ( NEJM 2003;348:1083-4). It said, “When a medical mistake receives this much attention, it affects the medical profession and …
Contribution of parental blood pressures to association between low birth weight and adult high blood pressure: cross sectional study
Authors: B. R Walker, A. McConnachie, J. P Noon, D. J Webb, G. C M Watt
Journal: BMJ (1998)

To examine the possibility that low birth weight is a feature of the inherited predisposition to high blood pressure.Cross sectional study.Primary care medical centre in Edinburgh.One offspring of 452 families (231 men and 221 women aged 16-26 years) in whom blood pressure, weight, and height were measured in 1986 and whose parents had blood pressure measured in 1979. Birth weights were obtained from case records (270 offspring) or by questionnaires sent to the mothers (182 offspring).Birth weight and adult systolic blood pressure in offspring in relation to parental blood pressure.If parental blood pressures were not considered, a 1 kg decrease in birth weight was associated with a 2.24 mm Hg increase in systolic blood pressure of offspring (P = 0.06) after correction for current weight and sex. However, parental blood pressures correlated positively with blood pressure of offspring, and higher maternal blood pressure was associated with lower birth weight (-3.03 g/mm Hg, P < 0.01). After correction for parental blood pressures, a 1 kg decrease in birth weight was associated with only a 1.71 mm Hg increase in the systolic blood pressure of the offspring (P = 0.15).Low birth weight is a feature of the inherited predisposition to hypertension, perhaps because it is associated with higher maternal blood pressure during pregnancy. Parental blood pressure may be an important confounding factor in the relation between low birth weight and subsequent hypertension.
Gender differences in advanced heart failure: insights from the BEST study
Authors: Jalal K Ghali, Heidi J Krause-Steinrauf, Kirkwood F Adams, Steven S Khan, Yves D Rosenberg, Clyde W Yancy, James B Young, Steven Goldman, Mary Ann Peberdy, JoAnn Lindenfeld
Journal: Journal of the American College of Cardiology (2003)
Downregulation of Renal Sodium Transporters and Tonicity-Responsive Enhancer Binding Protein by Long-Term Treatment with Cyclosporin A
Authors: Sun Woo Lim, Kyung Ohk Ahn, Mee Rie Sheen, Un Sil Jeon, Jin Kim, Chul Woo Yang, H. Moo Kwon
Journal: Journal of the American Society of Nephrology (2007)

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/tonicity of the renal medullary interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.
Association between Glycemic State and Lung Function
Authors: Robert E. Walter, Alexa Beiser, Rachel J. Givelber, George T. O'Connor, Daniel J. Gottlieb
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Diabetes mellitus has been inconsistently associated with a reduced level of pulmonary function. To elucidate this association further, we analyzed the relationship of diabetes and of fasting blood glucose to the level of pulmonary function assessed by spirometry in the 3,254 members of the Framingham Offspring Cohort. Diabetes was defined as a fasting blood glucose of 126 mg/dl or more or pharmacologic treatment. Subjects were classified as current, former, or never smokers based on questionnaire responses. Predicted pulmonary function was determined from the coefficients of a regression of pulmonary function on age, sex, and body habitus in the 1,110 never smokers. Both the diagnosis of diabetes and a higher level of fasting blood glucose were associated with lower than predicted levels of pulmonary function. The adverse effect of diabetes and glycemic level on pulmonary function was stronger among ever smokers than never smokers, suggesting an interaction between the level of fasting glycemia and tobacco smoking.
Treatment of Postpartum Hemolytic Uremic Syndrome With Plasma Exchange
Authors: Cory D. Spencer
Journal: JAMA (1982)

POSTPARTUM hemolytic uremic syndrome (HUS) is a rare disease with a reported mortality of 61%.<sup>1</sup>Heparin and antiplatelet agents are of unproved benefit in the treatment of HUS.<sup>2,3</sup>Recently Remuzzi and co-workers<sup>4</sup>demonstrated reversal of hemolysis and thrombocytopenia within 48 hours after a single plasma exchange in two middle-aged women with severe hypertension and HUS. The present report describes the treatment of HUS in a postpartum patient with plasma exchange alone, documenting the promptness with which it reversed hemolysis and thrombocytopenia in this setting. <h3>Report of a Case</h3> A 23-year-old woman (gravida 4, para 2, abortus 1) was seen at another hospital in her 34th gestational week with acute abdominal pain. She was preeclamptic. Her hematocrit reading was 20% and platelet count was 113,000/cu mm. She received packed RBCs and 2 units of fresh-frozen plasma. Five hours after admission she was spontaneously delivered of a stillborn infant
External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study
Authors: Daniel YC Heng, Wanling Xie, Meredith M Regan, Lauren C Harshman, Georg A Bjarnason, Ulka N Vaishampayan, Mary Mackenzie, Lori Wood, Frede Donskov, Min-Han Tan, Sun-Young Rha, Neeraj Agarwal, Christian Kollmannsberger, Brian I Rini, Toni K Choueiri
Journal: The Lancet Oncology (2013)
The Burden of Treatment Failure in Type 2 Diabetes
Authors: Jonathan B. Brown, Gregory A. Nichols, Andrew Perry
Journal: Diabetes Care (2004)

OBJECTIVE—In type 2 diabetes, therapies to maintain blood glucose control usually fail after several years. We estimated the glycemic burden that accumulates from treatment failure and describe the time course and predictors of failure. RESEARCH DESIGN AND METHODS—A prospective, population-based study using retrospective observational data. We identified all 7,208 complete courses of treatment with nondrug therapy, sulfonylurea monotherapy, metformin monotherapy, and combination oral antihyperglycemic therapy between 1994 and 2002, inclusive, among members of the Kaiser Permanente Northwest Region. We calculated mean cumulative glycemic burden, defined as HbA1c-months &amp;gt;8.0 or 7.0% for each treatment. We then measured the likelihood that the next HbA1c would exceed 8.0 and 7.0% after HbA1c exceeded each of ten hypothetical treatment thresholds. Finally, we estimated multivariate logistic regression models to predict when HbA1c would continue to deteriorate. RESULTS—In this well-controlled population, the average patient accumulated nearly 5 HbA1c-years of excess glycemic burden &amp;gt;8.0% from diagnosis until starting insulin and about 10 HbA1c-years of burden &amp;gt;7.0%. Whenever patients crossed the American Diabetes Association-recommended treatment threshold of 8.0%, their next HbA1c result was as likely to be &amp;lt;8.0 as &amp;gt;8.0%. Multivariate prediction models had highly statistically significant coefficients, but predicted &amp;lt;10% of the variation in future HbA1c results. CONCLUSIONS—Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail. An action point at 7.0% or lower is more likely to prevent additional deterioration than the traditional action point of 8.0%.
Anti—pre-S responses and viral clearance in chronic hepatitis B virus infection
Authors: Agata Budkowska, Pascal Dubreuil, Thierry Poynard, Patrick Marcellin, Marie-Anne Loriot, Patrick Maillard, Jacques Pillot
Journal: Hepatology (1992)

Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S1 and pre-S2 antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S1 and anti-pre-S2 antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B virus from serum.
Puerperal Eclampsia: A Comparison with Venom Poisoning and a Suggestion for Treatment following therefrom
Authors: H. L. Murray
Journal: BMJ (1911)

BORNms 8 Calabar.An undoubted case occurred in the Nears 1830-1. Bonny.In 1873 several deaths were recorded which might have been due to yellow fever.In 1883 it is stated that an outbreak of yellow fever occurred, due to importation from Freetown.In 1890-1 a very serious outbreak is recorded of what was unquestionably yellow fever.The medical officer, Dr. Parker, was certain that it was genuine yellow fever.The description of the symptoms is such as to leave no doubt as to the nature of the disease-the disease was thought by some to be malignant malaria, and was attri- buted to the pulling down of an old factory; others main- tained that it was introduced in the straw and litter on a ship coming from South America.The natives were not affected.There were 11 cases and 9 deaths amongst the population of 15 white men.Dr. A. J. Brown, who was in Bonny at the time, informs me that he attended two of the cases.The symptoms were headache, pain, great prostration, albuminuria, yellowness, persistent black vomiting.Dr. Parker, who was the medical officer at the time, stated that he was convinced that the disease was yellow fever.He subsequently contracted the disease and died.Dr. MacDonald, Bonny, has furnished me with notes of a suspicious case which occurred in 1909, six weeks after arrival in Bonny.The diagnosis at the time was "gastritis and jaundice."No malarial parasites were, however, found in the specimens of blood which were repeatedly examined.From numerous inquiries which I have made, there can be no doubt that yellow fever occurred in Lagos in a virulent form from 1894 to 1895.Thus, I have it on reliable authority that seventeen members of a mission arrived from England in Lagos on December 13th, 1893.Of these, five had died by the end of January, 1894.In addition, a resident missionary, and the young child of another missionary, had also died.The cases presented the classical symptoms of yellow fever.According to Ott, cases were reported at Lagos in 1896.At Sapoli in 1898-9, there were a considerable number of suspicious deaths, and in 1907 an outbreak of a severe type of fever was recorded at Widah.Examination of the medical notes in the hospital at Lagos convinces me that genuine well-marked cases of yelTow fever occurred in the years 1902-5.There were also many mild cases.The symptoms recorded are violent headache and body pains, high temperature, slow pulse, suppression of urine, black vomit, and coma, terminating fatally.In 1905 the symptoms recorded could hardly be those of any other disease but yellow fever, yet the diagnosis made at the