tbuckley/cabot-search huggingface dataset:
Treating erectile dysfunction when PDE5 inhibitors fail
Authors: Chelsea N McMahon, Christopher J Smith, Ridwan Shabsigh
Journal: BMJ (2006)

New oral drugs, especially phosphodiesterase type 5 (PDE5) inhibitors, have revolutionalised the treatment of erectile dysfunction by decreasing reliance on more invasive options. These inhibitors compete with cyclic GMP (guanosine monophosphate) for the PDE5 receptor site. Sexual arousal activates the nitric oxide-cyclic GMP pathway, leading to relaxation of cavernosal smooth muscle cells, engorgement of lacunar spaces, and erection. PDE5 hydrolyses cyclic GMP to 5-GMP, which terminates the pathway and produces detumescence, so that PDE5 inhibitors result in increased intracellular concentrations of cyclic GMP and erection.

Three potent selective PDE5 inhibitors (sildenafil (Viagra; Pfizer), tadalafil (Cialis; Lilly), and vardenafil (Levitra; Bayer)) are currently available. Although large multicentre clinical trials have shown the efficacy and tolerability of these drugs in erectile dysfunction with various aetiologies and a broad range of severity, 30-35% of patients fail to respond. The reported 62% prescription renewal rate at three to four months of follow-up, which dropped to around 30% by 6-12 months, suggests that patients stop taking the drug for reasons other than failure of treatment.1

The reasons for acute or delayed failure include severe erectile dysfunction at presentation, worsening of endothelial dysfunction and progression of penile atherosclerosis, erectile dysfunction after radical prostatectomy, unrecognised hypogonadism, inadequate patient education and incorrect drug usage, the development of tachyphylaxis (drug tolerance), and psychosocial factors. Alternative treatment methods, education on the use of the drug, androgen replacement, lifestyle changes, correction of risk factors, and relationship or psychosexual counselling have been reported.

We searched PubMed and Medline for papers published from January 1980 to May 2005, using the term “erectile dysfunction”. We selected papers (published in English) on the management of erectile dysfunction and erectile dysfunction that does not respond to oral drugs. We review the treatment options available to primary care doctors and specialists who treat sexual dysfunction and …
"Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype.
Authors: T F Gajewski, D W Lancki, R Stack, F W Fitch
Journal: The Journal of Experimental Medicine (1994)

Mature CD4+ helper T lymphocytes have been categorized into two major functional phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which are thought to arise from a pluripotential precursor cell termed TH0. Clonal anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR) complex in the absence of a costimulator molecule; however, anergy has been difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0 lines with anergizing stimuli results in the selective loss of TH1 characteristics and retention of a TH2 phenotype. Treated cells exhibit a substantial reduction in interleukin 2 (IL-2) production and antigen-specific cytolytic activity, but retain comparable IL-4 and IL-5 production in response to restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also increase in size, thus morphologically resembling TH2 cells. The signaling characteristics of these cells also are altered, in that they exhibit an elevated basal level of intracellular free calcium which fails to increase significantly with subsequent restimulation, reminiscent of the signaling characteristics of TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells may arise when TH0 cells are stimulated via the TCR complex in the absence of a putative costimulator molecule.
Severe acute respiratory syndrome: Imported cases of severe acute respiratory syndrome to Singapore had impact on national epidemic
Authors: A. Wilder-Smith
Journal: BMJ (2003)

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular junctions where thymus plays a pathogenetic role. Thymectomy benefits patients, and thymic hyperplasia, a lymphoid infiltration of perivascular spaces becoming site of autoantibody production, is recurrently observed. Cytokines and chemokines, produced by thymic epithelium and supporting survival and migration of T and B cells, are likely to be of great relevance in pathogenesis of thymic hyperplasia. In thymic epithelial cell (TEC) cultures derived “in vitro” from normal or hyperplastic age-matched MG thymuses, we demonstrate by gene profiling analysis that MG-TEC basally overexpress genes coding for p38 and ERK1/2 MAPKs and for components of their signaling pathways. Immunoblotting experiments confirmed that p38 and ERK1/2 proteins were overexpressed in MG-TEC and, in addition, constitutively activated. Pharmacological blockage with specific inhibitors confirmed their role in the control of IL-6 and RANTES gene expression. According to our results, IL-6 and RANTES levels were abnormally augmented in MG-TEC, either basally or upon induction by adhesion-related stimuli. The finding that IL-6 and RANTES modulate, respectively, survival and migration of peripheral lymphocytes of myasthenic patients point to MAPK transcriptional and posttranscriptional abnormalities of MG-TEC as a key step in the pathological remodelling of myasthenic thymus.
Lack of ‘appropriately assessed’ patient-reported outcomes in randomized controlled trials assessing the effectiveness of interventions for rosacea
Authors: E.J. van Zuuren, Z. Fedorowicz
Journal: British Journal of Dermatology (2012)

Funding sources: none. Conflicts of interest: none declared. Madam, Rosacea is a chronic skin disease, and psychological problems are fairly common in people affected by rosacea. The persistent red pimply rash on the face can be a source of embarrassment, anxiety and low self‐esteem. It may instil a lack of confidence and even lead to depression or body dysmorphic disorder. Rosacea can also have a significant negative impact on health‐related quality of life (HRQoL).We have documented the patient‐reported outcomes (PROs) used in clinical trials identified in the Cochrane Review on the effectiveness of interventions for rosacea, published in the Cochrane Library March 2011, and we reported their measurement properties previously.1 Here we discuss the results. We independently evaluated the PROs in 58 included studies using the ‘Checklist for describing and assessing patient‐reported outcomes in Clinical Trials’, as described in the Cochrane Handbook for Systematic Reviews of Interventions.2 We extracted from the primary report details of the number of items or domains, the type of rating scales used, the timing of the assessments and whether symptoms were presented as scores at baseline or at follow‐up or both, as well as any measurement property that we identified. We abstracted estimates of effect on PROs and applied GRADE (Grades of Recommendation Assessment, Development and Evaluation) methodology to create evidence profiles, summarizing results and confidence in effect estimates (all data available on request).3
THE ROLE OF ACIDURIA IN THE DEVELOPMENT OF HEMOGLOBINURIC NEPHROSIS IN DEHYDRATED RABBITS
Authors: Joseph J. Lalich, Seymour I. Schwartz
Journal: The Journal of Experimental Medicine (1950)

The effect of acid diets, fasting, and dehydration on the urine pH and the kidneys was determined in 11 control animals. Hyaline casts in the collecting tubules and interstitial medullary edema were observed in the 8 that survived. The test rabbits were subjected to the same treatment as the controls but, in addition, received 1.8 gm./kilo of intravenous homologous hemoglobin. Eleven of 18 animals died of hemoglobinuric nephrosis. The rabbits which died of hemoglobinuric nephrosis exhibited significant alterations in two or more of the following: kidney weight, pigment cast accumulation, and elevations of NPN. The theories which have been advanced to explain the pathogenesis of hemoglobinuric nephrosis are evaluated in the light of the present observations. It is proposed on the basis of them that antecedent tubular damage is of primary importance in the pathogenesis of hemoglobinuric nephrosis.
European parliament wants world ban on human cloning
Authors: R. Watson
Journal: BMJ (1997)

The European parliament has called for a worldwide ban on the cloning of human beings after the successful cloning of a sheep by a research team based in Scotland (1 March, p 623).

But despite strong pressure from Green MEPs, the parliament has rejected efforts to apply a similar ban to animal cloning. Instead, it has urged the European Union to consider legislation that would set out clear …
MEDICAL COLLEGES AND PROFESSIONAL STANDARDS.
Authors: INEZ C. PHILBRICK
Journal: JAMA (1901)

According to the report of the United States Commissioner of Education, in 1899, there were in that year 23,778 medical students and 4911 medical graduates. Between 1875 and 1899 the increase in the number of medical students was 177 per cent. But not alone upon statistics do we depend for confirmation of the crowded state of the profession. The fact is so patent and alive that much of the editorial space of leading medical journals is devoted to a discussion of the condition, its cause and its cure. That a majority of the profession is incompetent and unworthy, is not subject to statistical proof. To the unprejudiced medical observer of the profession of almost any locality, the truth is patent that very many of its members are persons of inferior ability, questionable character and coarse and common fiber. The little esteem in which the profession is held by laity and
Number of people in UK with dementia will more than double by 2050
Authors: Oona Mashta
Journal: BMJ (2007)

The number of people with dementia, which currently costs the United Kingdom £17bn (€25bn; $33bn) a year, will increase from 700 000 at present to more than a million in less than 20 years and to 1.7 million by 2050, creating a potential medical and social crisis, a new report says.

The report by the Alzheimer's Society into the social and economic costs of dementia warns that urgent action is needed to plan for the rapid increase in the number of people in the UK with the illness.

It calls for better investment in dementia research and services and more efficient use of …
High Blood Pressure as Risk Factor in Diabetic Retinopathy Development in NIDDM Patients
Authors: Masaki Ishihara, Yaichiro Yukimura, Toru Aizawa, Takashi Yamada, Ken Ohto, Kunio Yoshizawa
Journal: Diabetes Care (1987)

The correlation between diabetic retinopathy and blood pressure was analyzed in 742 type II diabetic patients. Systolic and pulse blood pressures were significantly higher in the patients with retinopathy than in those without (mean systolic pressure 142 vs. 139 mmHg, P &amp;lt; .01; mean pulse pressure 60.5 vs. 56.4 mmHg, P &amp;lt; .001). There was no difference in the diastolic blood pressure between these two groups. The correlation between blood pressure and the components of retinopathy (including microaneurysms, hemorrhages, and exudates) was also analyzed. Even when the patient with microaneurysms or dot hemorrhages, blot hemorrhages, or hard or soft exudates were separately evaluated, systolic and pulse blood pressures were higher in those with one of these diabetic changes than in patients without them. To avoid the influence of nephropathy, the patients were divided into nonproteinuric or proteinuric groups. In the nonproteinuric group, pulse blood pressure was higher in patients with retinopathy than in those without. In the proteinuric group, systolic blood pressure was also higher in patients with retinopathy than in those without. However, these observed differences in blood pressure were slight after the division of the patients. With respect to the components of retinopathy, systolic and pulse blood pressures were significantly higher in the patient with blot hemorrhages than in those without in both nonproteinuric and proteinuric groups (nonproteinuric: systolic pressure 142 vs. 137 mmHg, P &amp;lt; .005, and pulse pressure 60.4 vs. 55.5 mmHg, P &amp;lt; .001; proteinuric: systolic pressure 155 vs. 146 mmHg, P &amp;lt; 0.01, and pulse pressure 69.0 vs. 63.5 mmHg, P &amp;lt; .05) In regard to other components (microaneurysms, dot hemorrhages, or hard or soft exudates), no significant difference was found in blood pressure when analyzed in both nonproteinuric and proteinuric patients. Systolic, diastolic, and pulse blood pressures did not correlate with blood glucose level in any of our patients. These data revealed that systolic hypertension is a risk for diabetic retinopathy, especially for blot hemorrhage.
Breast cancer prevention: a review of current evidence
Authors: V. G. Vogel
Journal: CA A Cancer Journal for Clinicians (2000)

The National Cancer Institute has created a breast cancer risk assessment tool that quickly estimates a woman's individualized absolute risk of developing breast cancer. Understanding the magnitude of risk is important because recent data show that breast cancer incidence may be reduced. All women may improve their overall health and thus perhaps minimize breast cancer risk by maintaining a healthy weight, avoiding cigarettes, limiting alcohol consumption, getting regular exercise, and avoiding non-diagnostic ionizing radiation. Nevertheless, no lifestyle modifications have yet been proven to prevent or definitively lower the risk of breast cancer. In addition, women whose personal breast cancer risk is high may consider reducing risk by pharmacologic or surgical means. In such women, a five-year course of tamoxifen reduced the risk of invasive breast cancer by 49%; women with lobular carcinoma in situ or atypical hyperplasia experienced even greater risk reductions. Because of the potential for vascular and endometrial side effects, women who are candidates for a preventive course of tamoxifen must be counseled regarding its relative risks and benefits. Prophylactic mastectomy offers at least a 90% reduction in the risk of breast cancer, but the physical and psychological changes involved in such a procedure make it a difficult choice for many women. Breast cancer risk assessment and appropriate counseling are becoming standard components of breast cancer screening and overall health maintenance.
Porphyrins in Stools
Authors: H. D. Barnes, G. Dean
Journal: BMJ (1959)

Because of heavy pressure on our space, correspondents are asked to keep their letters short.Alpha-Chymotrypsin in Cataract Surgery SIR,-With reference to your recent annotation on alpha-chymotrypsin in cataract surgery (Journal, August 1, p. 120), a note of caution must be sounded on the reported absence of complications; for I have seen a case of corneal vascularization following the use of this enzyme in the anterior chamber.'Fortunately it was not severe enough to impair the vision.It is too early to appraise this new technique in cataract surgery, and at present it would seem advisable to restrict it to properly controlled trials, and cases where it is essential in order to obtain an intracapsular extraction.-Iam, etc.,
The Limitations of “Vulnerability” as a Protection for Human Research Participants
Authors: Carol Levine, Ruth Faden, Christine Grady, Dale Hammerschmidt, Lisa Eckenwiler, Jeremy Sugarman
Journal: The American Journal of Bioethics (2004)

Vulnerability is one of the least examined concepts in research ethics. Vulnerability was linked in the Belmont Report to questions of justice in the selection of subjects. Regulations and policy documents regarding the ethical conduct of research have focused on vulnerability in terms of limitations of the capacity to provide informed consent. Other interpretations of vulnerability have emphasized unequal power relationships between politically and economically disadvantaged groups and investigators or sponsors. So many groups are now considered to be vulnerable in the context of research, particularly international research, that the concept has lost force. In addition, classifying groups as vulnerable not only stereotypes them, but also may not reliably protect many individuals from harm. Certain individuals require ongoing protections of the kind already established in law and regulation, but attention must also be focused on characteristics of the research protocol and environment that present ethical challenges.
Finding knizocytes in a peripheral blood smear
Authors: Jean François Lesesve, Loïc Garçon, Thomas Lecompte
Journal: American Journal of Hematology (2011)

A 61-year-old female with unremarkable medical history and no evidence of chronic alcohol abuse presented with acute liver failure secondary to massive paracetamol overdose. Laboratory tests indicated: Hb 11.5 g/dL (reference value, RV ≥ 12), WBC 13.8 × 109/L (RV ≤ 10), platelets 45 × 109/L (RV ≥ 150), bilirubin 238 μmol/L (RV ≤ 25), GOT/ASAT 210 UI/L (VR < 30), GPT/ALAT 103 UI/L(RV < 40), alcaline phosphatase 212 UI/L, RV < 120), cholesterol 3.2 mmol/L (RV ≤ 3.9), and triglycerids 6.5 mmol/L (RV ≤1.7). The plasma did not show visible hemolysis. Blood smear (Image 1, May Grünwald Giemsa, ×1000) demonstrated numerous knizocytes in a background of moderate poïkilocytosis. Mosaic image of knizocytes (May-Grünwald-Giemsa 1000×). Knizocytes are triconcave RBCs with a “ridge,” a “bridge” separating the three concavities (in scanning electron micrograph), or a strip of hemoglobin crossing the clear central area (in standard staining). They are very rarely observed in routine practice even if their percentage was estimated once 0.6% ± 0.5 in healthy controls (min-max values: 0–2.5%) [1]. By contrast, they are regularly seen in newborns where they are considered as relatively young RBCs with impaired membrane deformability usually among stomatocytes, spherocytes, and erythrocytes with spicules and protrusions (echinocytes/acanthocytes) [2]. In adults, they are mainly observed in the context of anomalies of the cholesterol metabolism related to any acute liver dysfunction. As the RBCs morphology is influenced by the membrane lipid content and as RBCs exchange continuously lipids with plasma [3], change in circulating lipids levels associated with acute liver disease can alter the RBCs shape, in a delay shorter than their lifetime, as recently reported in this journal [4] or by others [5]. More chronically, knizocytes and/or target cells are observed in patients with familial lecithin/cholesterol acyltransferase deficiency, which induce a decrease in the membrane deformability and as a consequence a higher RBCs fragility [4, 6]. Knizocytes are also frequently observed in chronic liver diseases as chronic hepatitis or cirrhosis (alcoholic or postviral causes) where they can account for up to 15% of the red cells [7]. Alcohol abuse induce a variety of changes in the RBC morphology, including typically round macrocytes, stomatocytes but also knizocytes related to the presence of acetaldehyde-derived epitopes both on the cell membrane and inside the RBCs [8]. Although nonspecific, observation of knizocytes on a blood smear should prompt an assessment of liver function and lipid parameters.
Determinants of Impairment of Cardiac Filling During Progressive Pericardial Effusion
Authors: WILLIAM E. NERLICH
Journal: Circulation (1951)

The progressive reduction in cardiac output—and later in arterial pressures—that develops during advancing degrees of pericardial effusion is usually attributed to a steady decrease in the venoatrial pressure gradient. Evaluation of changes in instantaneous pressures in the right and left atria at the end of ventricular diastole (Z pressure) and systole (V pressure) indicates that as pericardial pressure rises other determinants enter in the following order: (1) reduction in diastolic capacities of the atriums and ventricles; (2) decrease in venoatrial pressure gradient and preponderant rise of left atrial pressures due to the higher elasticity coefficient of this chamber; (3) blockage of atrial inflow during ventricular diastole; (4) impairment of atrial inflow during ventricular systole as its stroke volume diminishes to an extreme degree; and (5) inauguration of a vicious cycle in which a diminishing venopressure gradient decreases ventricular filling, while the consequent reduction in stroke volume attenuates the facilitating effect of ventricular ejection on the venoatrial gradient.
Continuous Perfusion of Bile and Protease Activators Through the Pancreas
Authors: T. Malcolm Robinson, J. Englebert Dunphy
Journal: JAMA (1963)

INVESTIGATIONSto the reflux of bile as a factor in pancreatitis by techniques which involve direct cannulation of the pancreatic duct and the injection of bile and other substances into the gland are subject to numerous inconsistencies and criticisms.<sup>1,2</sup>To obviate some of these problems, methods have been described in the dog and the goat for the in vivo perfusion of the gland at pressures which are not artificial.<sup>2-5</sup>In these techniques all of the animal's bile is perfused through the gland. It has been stated<sup>5</sup>that this technique of in vivo perfusion allows for the mixing of bile salts and activated trypsin to occur within the pancreas.<sup>6</sup>Recently, however, the suggestion was advanced that bile is not only a relatively poor protease activator but may actually afford some protection in vivo against protease auto activation.<sup>2</sup> In the present study a model was prepared in
Bacteriuria During Indwelling Catheter Drainage
Authors: George F. Thornton
Journal: JAMA (1966)

Thirty-three patients requiring prolonged drainage of the urinary bladder in 35 separate instances were treated with a constant bladder irrigation of a dilute solution of neomycin sulfate and polymyxin B sulfate. This system was highly effective in preventing the acquisition of bacteriuria caused by gram-negative rod forms in patients with initially sterile urine if the catheter remained in place for ten days or less, but it was considerably less effective in preventing acquired bacteriuria when catheter drainage was required for periods in excess of ten days. The bladder rinse was not effective in eradicating preexisting bacteriuria. Although complications of therapy were minimal, prolonged irrigation with neomycin-polymyxin B solution seemed to predispose to acquired bacteriuria or superinfection with<i>Proteus</i>species and enterococci which were usually resistant to at least one of these antibiotics.
19 HOW ARE HEPATOCYTES PRIMED FOR TGF-β MEDIATED APOPTOSIS? BONE MORPHOGENETIC PROTEIN (BMP)-9 AS DEADLY CO-FACTOR IN VITRO AND IN VIVO
Authors: K. Breitkopf-Heinlein, Q. Li, A. Mueller, P. ten Dijke, S. Dooley
Journal: Journal of Hepatology (2012)
Ileorectal anastomotic obstruction treated with a dual endoscopic transillumination technique
Authors: J. Koo, S. Park, H. Yim, J. Um, H. Lee, S. Lee, J. Choi
Journal: Endoscopy (2009)

A 37-year-old woman with refractory constipation underwent a laparoscopic total colectomy with an ileorectal anastomosis. The ileorectal anastomosis was constructed with a circular stapler and protected with a loop ileostomy. Two months later the patient was due to undergo ileostomy closure but fluoroscopic examination showed complete obstruction of ileorectal anastomosis ([Fig. 1]).
Hiatal Hernia With Reflux Resulting in False Positive Iodine-131 Scan
Authors: MICHELLE M. McNAMARA, H. PETER TSANG
Journal: Clinical Nuclear Medicine (1998)

Iodine-131 imaging is an important diagnostic tool in the evaluation and management of patients who have undergone treatment for differentiated thyroid cancer. The specificity is reported to be 60-80%, and the sensitivity greater than 90%. The clinician must be alert to both physiologic and nonphysiologic tracer distributions, which may mimic recurrent or metastatic disease.