tbuckley/cabot-search huggingface dataset:
Randomized Comparison of Strategies for Reducing Treatment in Mild Persistent Asthma
Authors: Stephen P Peters, Nicholas Anthonisen, Mario Castro, Janet T Holbrook, Charles G Irvin, Lewis J Smith, Robert A Wise
Journal: New England Journal of Medicine (2007)

Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the "stepping down" of therapy to the minimum needed to maintain control of asthma. Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast (our primary hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary hypothesis) has not yet been determined.We randomly assigned 500 patients with asthma that was well controlled by inhaled fluticasone (100 microg twice daily) to receive continued fluticasone (100 microg twice daily) (169 patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was administered for 16 weeks in a double-blind manner. The primary outcome was the time to treatment failure.Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups.Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. A switch to montelukast results in an increased rate of treatment failure and decreased asthma control; however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].).
Open-Loop Intravenous Insulin Waveforms for Postprandial Exercise in Type I Diabetes
Authors: P Poussier, B Zinman, E B Marliss, A M Albisser, K Perlman, D Caron
Journal: Diabetes Care (1983)

To obtain optimal metabolic control in diabetic individuals receiving open-loop insulin infusion, waveforms appropriate for exercise must be developed. The present study describes the responses of four nonobese type I diabetic individuals to a specific insulin waveform derived for postprandial exercise during intravenous open-loop insulin infusions. The open-loop system consisted of a silastic rubber reservoir, a programmable flow-rate controller, and a peristaltic pump connected by a silicone rubber catheter inserted into abranch of the external jugular vein. The basal insulin infusion rate (15 ± 0.5 mU/min) was adjusted to achieve fasting euglycemia (87 ± 7 mg/dl), and a three-step insulin infusion waveform to normalize the glycemic response to breakfast (peak glucose 127 ± 12 mg/dl at 45 min) was established. The three-step (each defined as S1, S2, S3) insulin waveform consisted of: S1, 30 ± 4 mU/min for 15 ± 3.5 min; S2, 58.7 ± 6.6 mU/min for 60 ± 4 min; S3, 33.7 ± 2.5 mU/min for 65 ± 12 min. When 45 min of moderate exercise (65 ± 6 W) wasperformed 30 min after the start of breakfast, symptomatic hypoglycemia occurred in all subjects (lowest mean glucose 49 ± 4 mg/dl) at varying times (65, 115, 180, and 180 min). The meal insulin waveform was then modified so that the infusion rate returnedto the premeal basal rate with the onset and for the duration of exercise, while at the conclusion of exercise, the remaining meal waveform was reinitiated. Under these circumstances, hypoglycemia was prevented and the meal glycemic excursion was entirely normalized.”Free“ immunoreactive insulin levels were significantly lower (P &amp;lt; 0.05) during exercise, consistent with the reduction in the infusion rate to basal with the modified meal insulin waveform. This insulin infusion waveform appears appropriate to normalize the glycemic response to postprandial exercise with open-loop intravenous insulin replacement.
SOME PRACTICAL POINTS ON THE TREATMENT OF PULMONARY TUBERCULOSIS.
Authors: J. EDWARD STUBBERT
Journal: JAMA (1902)

So much attention is at present being demanded by the prognosis and treatment of pulmonary tuberculosis that a few practical suggestions may be of interest to the members of this Association. <h3>THE EVOLUTION OF TREATMENT.</h3> There is so much uncertainty as to prognosis in different cases and such a wide divergence of opinion as to methods of handling curable cases, that great confusion necessarily exists in the mind of the general practitioner. Some tell us to send our patients to a high altitude, others to a cold climate, while many recommend a warm one; and again, some are in favor of ocean voyages. These various views were strongly advocated for a number of years so that climate alone was considered by many the only essential for the cure of the disease. In a small percentage of cases the results were satisfactory; in very many the histories of the patients after
Bleeding inflammatory polyp formation as a complication of argon plasma coagulation therapy on a flat gastric angiodysplasia
Authors: S. Islam, K. Tan
Journal: Endoscopy (2009)

Argon plasma coagulation (APC) ablation therapy is now the first-line treatment modality for flat vascular lesions (angiodysplasia) in the gastrointestinal tract [1]. Complications are rare, but there is one published case of hyperplastic polyp formation [2] and another reported by personal communication (DM Chaves, personal communication cited in [2] [5]), while mild antral stricture has been noted once [3]. We describe an inflammatory bleeding polyp (needing polypectomy) which developed 2.5 months after a single application of APC to a flat gastric antral vascular lesion.
Loss of Striatal Vesicular Monoamine Transporter Protein (VMAT2) in Human Cocaine Users
Authors: Karley Y. Little, David M. Krolewski, Lian Zhang, Bader J. Cassin
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The hypothesis that human cocaine users lose vesicular monoamine transporter (VMAT2) protein was tested in striatal samples from cocaine users and age-, sex-, and postmortem interval-matched comparison subjects. METHOD: Striatal samples were retrieved at autopsy; immunoblot assays were then performed by using a highly specific VMAT2 antibody. Striatal radioligand binding to VMAT2 was assessed with dihydrotetrabenazine ([3H]DTBZ) and dopamine levels employing high-performance liquid chromatography. RESULTS: Cocaine users displayed a marked reduction in VMAT2 immunoreactivity as well as reduced [3H]DTBZ binding and dopamine levels. It did not appear that the reduction in VMAT2 immunoreactivity was related to ethanol use, but dopamine levels were lower in subjects with only ethanol diagnoses. Subjects suffering from cocaine-induced mood disorders displayed a greater loss of VMAT2 immunoreactivity that approached significance. CONCLUSIONS: Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely dependent patients.
Abstract A8: Mutation mapping in non-small cell lung cancer: A meta-analysis by geography and histology (MutMap)
Authors: Simon P. Dearden, James Stevens, Yi-Long Wu, David Blowers
Journal: Clinical Cancer Research (2012)

Abstract This study comprises a meta-analysis of publicly available and newly generated mutation data in non-small cell lung cancer patients to identify differences between histological subtypes and geographical populations. In addition to mutations in individual genes, comparisons are also made between mutation co-occurrences in these subgroups. These patterns of mutation co-occurrence have been termed The MutMap. Publications reporting mutation data on two or more genes, in histologically and geographically defined populations were identified. Assessments of single gene mutation frequencies and 2-gene mutation co-occurrences were performed in Western and Eastern populations. These were further separated into adenocarcinoma and squamous cell carcinoma histologies. In total, 21 studies were identified which matched the criteria above. In addition, data were generated at AstraZeneca and the Guangdong Lung Cancer Institute for inclusion in the meta-analysis. Mutation data were collated for 8 genes (EGFR, KRAS, TP53, LKB1, BRAF, PIK3CA, PTEN and ERBB2) in the 4 subgroups. Overall, mutations were more commonly reported in adenocarcinoma cases than squamous cell carcinoma cases. The most commonly mutated gene in NSCLC was TP53, however, mutation frequencies varied between Eastern and Western populations and between adenocarcinoma and squamous cell carcinoma cases. Mutations in EGFR were common (46.3%) in Eastern adenocarcinoma patients but rarer in Western cases (14.8%). Conversely KRAS mutations were more common in Western adenocarcinoma patients (25.7%) than Eastern cases (11.2%). Mutations in LKB1 were also more common in Western patients. Mutations in BRAF, PIK3CA and ERBB2 were rare in all NSCLC subgroups. Mutations in PTEN were common in Eastern squamous samples (9.8%) but rarer in the other 3 subtypes. Co-occurrences between mutations in 2 genes were also examined. As reported in other studies, mutations in EGFR and KRAS were exclusive to each other. In addition, in Western adenocarcinoma patients, mutations in both EGFR and LKB1 occurred significantly less often than would be expected by chance. There were several 2-gene mutation co-occurrences which were detected at levels &amp;gt;=5% of the NSCLC population, including TP53 with either KRAS or EGFR in adenocarcinoma and TP53 with LKB1 mutation in squamous cell carcinoma. Overall, this study confirms and expands the observation that mutation prevalence in NSCLC is complex, with variation not only between histological subtypes, but also between geographical populations. The co-occurrence of mutations may also be important in future treatment paradigms as clinically relevant segments of NSCLC possess both activating oncogenic driver mutations and mutations in tumour suppressor genes.
Percentage of Positive Biopsy Cores Can Improve the Ability to Predict Lymph Node Invasion in Patients Undergoing Radical Prostatectomy and Extended Pelvic Lymph Node Dissection
Authors: Alberto Briganti, Pierre I. Karakiewicz, Felix K.-H. Chun, Andrea Gallina, Andrea Salonia, Giuseppe Zanni, Luc Valiquette, Markus Graefen, Hartwig Huland, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2007)
Aberrant Ae (E beta) Ia polypeptide chain in H-2g2 haplotype mice. Possible result of an intragenic recombination or mutation.
Authors: P P Jones
Journal: The Journal of Experimental Medicine (1980)

Mice of strains D2.GD and B10.GD, which carry the recombinant haplotype H-2g2 (previously typed as H-2Kd I-Ad / I-Bb I-Jb I-Eb I-Cb Sb H-2Db), have an Ae (E beta) polypeptide chain electrophoretically distinct from the Ae chains of both b and d haplotype mice, including the progenitor strains from which the recombinant H-2g2 chromosome was derived. The evidence presented suggests that the altered molecular properties of the Aeg2 chain may be a consequence of an intragenic recombination event in the I-A subregion within the structural gene for this polypeptide chain. Because the A alpha and A beta chains controlled by H-2g2 appear to be d haplotype in origin, this finding would map the gene for Ae to the right of the loci controlling the A alpha and A beta chains
Therapeutic Possibilities in Cushing's Syndrome
Authors: James C. Melby
Journal: New England Journal of Medicine (1971)

Cushing's syndrome resulting from primary adrenocortical neoplasms or ectopic ACTH production from nonendocrine tumors is primarily treated surgically. Management of Cushing's disease due to excessive ACTH secretion by the pituitary gland —i.e., secondary bilateral adrenocortical hyperplasia — has been and remains a subject of dispute. The report by Orth and Liddle in this issue of the Journal compares the various modes of treatment in a large number of patients with Cushing's disease and provides an excellent evaluation of the therapeutic alternatives.Adrenalectomy for Cushing's disease has been the mainstay of treatment since 1945. Confusion about the nature of the pathogenesis . . .
Two Cases of Hydatid Disease of the Pleura
Authors: F. M. Rose
Journal: BMJ (1927)

HYDATID DISEASE OF, THE PLEURE E a more general trial, for I have confidence that if it be freely used,in rheumatic and other forms of streptococcal endocarditis it will very greatly lessen the incidence of valvular disease in these cases. IThe following brief notes of cases illustrate the method.Case 1.-In a case of obstinate chorea in a girl of 8 years, 10 grains of sodium sulphocarbolate were given every two hours.
Hepatitis C virus and human immunodeficiency virus coinfection in Spain
Authors: Bernardino Roca, Ignacio Suarez, Juan Gonzalez, Myriam Garrido, Belen de la Fuente, Ramon Teira, Paloma Geijo, Jaime Cosin, Salvador Perez-Cortes, Maria Jose Galindo, Fernando Lozano, Pere Domingo, Pompeyo Viciana, Esteban Ribera, Antonio Vergara, Trinitario Sánchez
Journal: Journal of Infection (2003)
A Reassessment of the Importance of Low-Count Bacteriuria in Young Women with Acute Urinary Symptoms
Authors: Calvin M. Kunin
Journal: Annals of Internal Medicine (1993)

Objective: To determine whether a statistical association exists between low-count bacteriuria (>102 to 104 colony-forming units/mL) and acute urinary symptoms in young women. Design: Prospective, case–control study. Setting: Gynecology clinic at a student health center. Patients: Women with or without urinary or vaginal symptoms. Measurements: History of urinary infections and sexual activity. Quantitative determination of bacteriuria and pyuria and bacterial species; urine leukocyte esterase test; specific gravity; creatinine levels; vaginal leukocytes; and in vitro culture of urine. Results: The frequency of recent sexual activity, pregnancies, and contraceptive practices was not statistically different between women with acute urinary symptoms and asymptomatic controls. Escherichia coli and Staphylococcus saprophyticus were the only microorganisms statistically associated with urinary symptoms and pyuria (P < 0.001). Low counts of these organisms were found in 10.2% of asymptomatic women. As the bacterial count increased, the association between these organisms and symptoms increased, and a step-wise increase occurred in the frequency and magnitude of pyuria, but the specific gravity and urine creatinine levels remained unchanged. Escherichia coli, even at low counts, grew well in the patients' own urine. Pyuria (>20 leukocytes/mm3) was present in 19.6% of asymptomatic women and was associated with vaginal leukorrhea. Conclusions: Low-count bacteriuria was statistically more frequent among young women with urinary symptoms than among asymptomatic controls. The low counts could not be explained by dilution of the urine or failure of the bacteria to grow well in the patients' urine. These findings suggest that the infection was not established in the bladder urine and that low-count bacteriuria might be an early phase of urinary tract infection.
A NEGLECTED DOCUMENT—THE MEDICAL RECORD OF THE STATE PSYCHIATRIC HOSPITAL PATIENT
Authors: BRUNO RADAUSKAS, ALBERT A. KURLAND, SIDNEY GOLDIN
Journal: American Journal of Psychiatry (1962)

Approximately 17,000 patient medical records were analyzed at the Spring Grove State Hospital over a 4-year period in order to determine what might be done to increase the usefulness of this document. The experiences and results reported by this study emphasized again and again that there are no substitutes for an adequately subsidized, staffed and maintained medical records department. Compromise in this area only compounds confusion, for slowly and insidiously the record is constantly changing in order to meet the development of new methods of treatment and care. This change uncontrolled will result in an increasingly costly and ineffective document. As more sophisticated instrumentation appears in the area of data processing and retrieval, the sound structure of a good medical document will become an increasingly important necessity.
Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content.
Authors: T Cotner, J M Williams, L Christenson, H M Shapiro, T B Strom, J Strominger
Journal: The Journal of Experimental Medicine (1983)

Cell-surface antigens that are induced to appear on T cells activated by the lectin phytohemagglutinin-P (PHA) can be classified both on the basis of the kinetics of their appearance and on their growth-association properties. Seven distinct T cell activation antigens, defined by monoclonal antibodies, were classified as early, intermediate, or late antigens based on their temporal appearance relative to DNA synthesis. Four antigens, the transferrin receptor, the T cell activation antigen Tac, the 4F2 antigen, and the 49.9 antigen were early antigens, whereas the OKT10 antigen appeared at intermediate times and both HLA-DR and antigen 19.2 appeared late. The use of a dye, Hoechst 33342, which stains DNA stoichiometrically, allowed the simultaneous analysis of immunofluorescence and cell cycle position of individual cells. This analysis unexpectedly revealed that essentially all cells in the proliferative phase of the cell cycle expressed each of the four early-activation antigens. The correlation between expression of the four early-activation antigens and T cell proliferation suggests that these molecules are important for the growth of all T cells. The relationship of two of these activation antigens, known to be the receptors for transferrin and interleukin 2, a T cell growth factor, is discussed with special reference to the roles of their ligands in supporting the growth of T cells.
S17 A pilot study of the prevalence of sleep disordered breathing (SDB) and nocturnal hypoxia in symptomatic adults with Sickle Cell Disease (SCD) and its relationship with disease severity
Authors: P. Murphy, R. Dillon, A. J. Williams, J. Howard, N. Hart
Journal: Thorax (2010)

<h3>Introduction</h3> There are few effective therapies available for the long-term management of the cardiac and renal sequelae of SCD. Identifying reversible factors, which exacerbate disease severity, would facilitate development of new therapies or novel applications of established treatments. Nocturnal hypoxia (NH) merits investigation as a disease modulating factor as it is established that hypoxia promotes polymerisation of sickle haemoglobin and this is reversible with oxygen therapy (Noguchi <i>et al</i>, 1993). Although NH is common in children with SCD and is associated with poor outcome, similar data for adults with SCD are lacking. This is the first study to determine the prevalence of OSA and NH and quantify the severity of NH in adults with SCD. In addition, we investigated the correlation between the degree of NH and organ dysfunction. <h3>Method</h3> Patients attending SCD clinic had an Epworth sleepiness score performed. Patients with either an ESS ≥10 or symptoms suggestive of SDB were offered nocturnal oximetry. Nocturnal oximetry findings were objectively scored and compared with the detailed clinical datasets collected at regular clinic attendances. OSA was defined as 4% oxygen desaturation index (4% ODI) of &gt;10 events/h and NH was defined as &gt;30% total sleep time (TST) with SpO<sub>2</sub> &lt;90%. <h3>Results</h3> 93 patients were screened. 34 had ESS ≥10 or clinical symptoms suggestive of SDB. 22 underwent nocturnal oximetry; mean ESS 12±4, clinic SpO<sub>2</sub> 96±4%, 4% ODI 8±6 events/h, nocturnal SpO<sub>2</sub> 91±4%, %TST SpO<sub>2</sub> &lt;90% 43±41%. Prevalence of OSA and NH was 59%. The degree of nocturnal hypoxia was correlated with urine protein:creatinine (r=−0.35, p=0.02), elevated pulmonary artery systolic pressure (r=−0.71; p=0.0001) and prevalence of priapism (p=0.004). There was no difference detected in frequency of painful crises or hospital admission in patients with significant NH compared to those without NH. <h3>Conclusion</h3> This small pilot study showed that OSA and NH had a prevalence of 59% in symptomatic adult SCD patients. These data have demonstrated a correlation between the severity of nocturnal hypoxia and pulmonary hypertension, renal impairment and priapism. These observations have not previously been reported. The strength of these correlations could suggest a causal relationship, although this needs to be confirmed in a larger prospective trial. Future studies should investigate the relationship between OSA, nocturnal hypoxia and organ dysfunction and need to be focussed on interventions such as nocturnal oxygen and continuous positive airway pressure.
Microscopic colitis in primary care
Authors: K. R Mahtani, P. W Rose, N. v. Someren
Journal: BMJ (2010)

A 70 year old man presented to his general practitioner in December 2008 because of a nasal sinus problem. He also mentioned that his stool frequency had increased to three to four times a day, which was unusual for him. These symptoms were associated with increased flatulence and occasional cramping, but he gave no history of passing blood per rectum. His examination was unremarkable, so he was started on a course of mebeverine and asked to return if his symptoms persisted. In February the patient consulted again, specifically about his diarrhoea. He still had episodes of diarrhoea, often three to four times a day, which lasted a few days and occurred two or three times each month before spontaneous resolution. His medical history, family history, and drug history were also unremarkable. His examination was again unremarkable and he had not lost weight. He was sent for a blood test at the practice. Liver function, C reactive protein, thyroid and endomysial IgA antibodies (he had been on a gluten containing diet) tests were all normal. His full blood count showed a haemoglobin of 129 g/l, mean corpuscular volume of 90.8 fl, and a total white cell count of 4.1×109/l. Because of the change in bowel habit and his age he was referred to the local colorectal team via the two week wait system. The patient underwent oesophagogastroduodenoscopy and colonoscopy with biopsy to exclude malignancy. Oesophagogastroduodenoscopy and colonoscopy were macroscopically normal. His colon histopathology report showed increased collagen deposition below the surface epithelium, intraepithelial lymphocytosis, and a moderate excess of chronic inflammatory cells in the lamina propria. No dysplastic or malignant changes, parasites, or granulomatous changes were seen. The appearances were thought to be consistent with microscopic colitis of combined collagenous and lymphocytic colitis type.
STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90α and β in multiple myeloma cells, which critically contribute to tumor-cell survival
Authors: Manik Chatterjee, Sarika Jain, Thorsten Stühmer, Mindaugas Andrulis, Ute Ungethüm, Ralf-Jürgen Kuban, Heike Lorentz, Kurt Bommert, Max Topp, Doris Krämer, Hans Konrad Müller-Hermelink, Hermann Einsele, Axel Greiner, Ralf C. Bargou
Journal: Blood (2006)