tbuckley/cabot-search huggingface dataset:
Intermittent Antibiotic Therapy for Nodular Bronchiectatic <i>Mycobacterium avium</i> Complex Lung Disease
Authors: Byeong-Ho Jeong, Kyeongman Jeon, Hye Yun Park, Su-Young Kim, Kyung Soo Lee, Hee Jae Huh, Chang-Seok Ki, Nam Yong Lee, Sung Jae Shin, Charles L. Daley, Won-Jung Koh
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited.To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for nodular bronchiectatic MAC lung disease.A retrospective cohort study of 217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung disease. All patients received either daily (n = 99) or intermittent therapy (n = 118) that included clarithromycin or azithromycin, rifampin, and ethambutol.Modification of the initial antibiotic therapy occurred more frequently in the daily therapy group than in the intermittent therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more frequently discontinued in the daily therapy group than in the intermittent therapy group (24 vs. 1%; P ≤ 0.001). However, the rates of symptomatic improvement, radiographic improvement, and sputum culture conversion were not different between the two groups (daily therapy vs. intermittent therapy: 75 vs. 82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In addition, the adjusted proportion of sputum culture conversion was similar between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P = 0.785).These results suggest that intermittent three-times-weekly therapy with a macrolide, rifampin, and ethambutol is a reasonable initial treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).
Left middle cerebral artery infarct in a young man with Crohn's disease
Authors: Dan Harris
Journal: Journal of the Royal Society of Medicine (2009)

A 38-year-old man was brought to A&E having collapsed at home after complaining of right-hand paraesthesia and discolouration. A self-employed plumber and smoker, he had been diagnosed with Crohn’s disease aged 18 years although he was not receiving any treatment at this time. On arrival 35 minutes post onset of symptoms he had a right-sided weakness plus inattention. His airway was patent, he was ventilating spontaneously (RR 24 breaths/min) and he was haemodynamically stable (pulse 90 bpm sinus rhythm, NIBP 115/65 mmHg). His Glasgow Coma Score (GCS) was 11/15 (Eyes 4, Verbal 2, Motor 5 [R]) with right-sided hypotonia and weakness (3/5) and upward right plantar reflex. Four minutes post arrival he vomited and dropped his GCS to 8/15 (Eyes 2, Verbal 1, Motor 5 [R]) which necessitated a rapid sequence induction of anaesthesia (propofol and suxamethonium) and tracheal intubation. The digits of his right hand were markedly discoloured with a capillary refill time of 5 seconds. His radial pulse was weakly palpable and ulnar pulse detectable on doppler examination. CT head with contrast performed 65 minutes post onset of symptoms showed low attenuation involving the insular cortex and lentiform nucleus with associated sulcal effacement consistent with an acute left middle cerebral artery territory infarct and no evidence of haemorrhage (Figure 1). He was given Alteplase (81 mg) 85 minutes post onset. A transthoracic echocardiogram (TTE) performed in A&E showed good biventricular function, no clots or masses, a normal aortic root and arch and no obvious patent foramen ovale although TTE cannot safely exclude such an abnormality. A repeat CT performed 8 hours post onset showed an increase in low attenuation. A CT aortogram performed to examine for great vessel dissection or occlusion found no abnormalities. Venous blood tests suggested probable active low grade Crohn’s disease despite his wife’s reports of no recent episodes (Hb 10.0 g/dL, MCV 70.9 fl, Plt 481 × 10/L, Alb 25 g/L, CRP 86 mg/L, Mg 0.67 mmol/L). On the ITU 23 hours post onset he developed signs of raised intracranial pressure (Pulse 65 bpm, IBP 200/100 mmHg). CT showed infarct progression with extensive attenuation reduction and accompanying mass effect with midline shift but still no haemorrhage. Brainstem testing was later performed with family present and he died 34 hours post onset of symptoms.
Influence of clinical factors, drug use, and food intake on the glutathione system
Authors: H Shirin
Journal: Gut (2002)

In a previous issue of Gut , Hoensch and colleagues ( Gut 2002; 50 :235–40) using antral and duodenal biopsies, reported on a variety of factors such as sex, age, drug use, and food intake that influence the concentration of glutathione and the activity of glutathione S-transferase. All of these factors either singly or in combination significantly affect glutathione metabolism within the gastric mucosa.

Curiously, one critical factor that may have influenced their measurements, namely Helicobacter pylori infection, was not mentioned in their paper. This omission is particularly important as the majority of the patients that these investigators examined had endoscopic findings strongly suggestive of infection with H pylori (gastric erythema, erosions, or ulcers). Previous studies by some of the coauthors in the Hoensch paper1,2 as well as by our group3 have clearly demonstrated that H pylori infection is associated with marked depletion by approximately 50% of reduced glutathione within the gastric epithelium, and that concentrations of reduced epithelial glutathione are restored to …
End-tidal CO2 for exclusion of suspected pulmonary embolism: a new partner for Wells?
Authors: D. Bonderman, I. M. Lang
Journal: European Respiratory Journal (2010)

Pulmonary embolism (PE) has been labelled as one of the leading causes of cardiovascular death in the Western World 1 and, still today, more than 40,000 patients in Germany and 200,000 in the USA die of acute PE each year. However, hospital mortality rates can fall from as high as 30% to 8% 2 when diagnosis and treatment are properly provided.

The diagnosis of PE remains a challenge because of highly variable clinical symptoms. Consequently, the diagnosis of PE has been finally confirmed in <35% of patients with a clinical suspicion of PE 3. A simple bedside test with the ability to exclude PE in patients who do not have it, while not overlooking true-positive cases, is desired and will prevent unnecessary exposure to contrast agents and radiation.

The assessment of alveolar dead space ventilation and the expired tracer gas CO2 as surrogates for pulmonary vascular obstruction have been proposed as valuable tools for excluding PE. The underlying pathophysiological principle is based on the three-compartment model of the …
Phase II Study of Erlotinib (OSI-774) in Patients With Advanced Hepatocellular Cancer
Authors: Philip A. Philip, Michelle R. Mahoney, Cristine Allmer, James Thomas, Henry C. Pitot, George Kim, Ross C. Donehower, Tom Fitch, Joel Picus, Charles Erlichman
Journal: Journal of Clinical Oncology (2005)

Purpose Epidermal growth factor receptor/human epidermal growth factor receptor 1 (EGFR/HER1) and ligand expression is frequently seen in hepatocellular cancers (HCCs). Erlotinib (Tarceva, OSI-774; OSI Pharmaceuticals, Melville, NY) is a receptor tyrosine kinase inhibitor with specificity for the EGFR/HER1. Methods The primary objective of this study was to determine the proportion of patients with advanced HCC who were progression-free at 6 months. Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was given continuously at a dose of 150 mg per day orally. Results Thirty-eight patients with HCC were enrolled. Median age of the patients was 69 years (range, 27 to 83 years). A majority of patients (63%) had an Eastern Cooperative Oncology Group performance status of 1. Forty-seven percent of patients had received prior chemotherapy for advanced HCC. EGFR/HER1 expression was detected in 88% of the patients. Median number of cycles per patient was two (range, 1 to 26). Twelve (32%; CI 95%, 18 to 49) of the 38 patients with HCC were progression-free at 6 months. Three patients had partial radiologic responses of duration of 2, 10, and 11 months, respectively. Disease control was seen in 59% of the patients. Median overall survival time was 13 months. Ten patients (26%) had toxicity-related dose reductions of erlotinib. Grade 3/4 skin toxicity or diarrhea was encountered in five and three patients, respectively. Conclusion Results of this trial suggest a benefit for EGFR/HER1 blockade with erlotinib in patients with HCC manifested by disease control. Additional studies with erlotinib as a single agent or in combination with other agents are warranted.
Advances in Urinary Proteome Analysis and Biomarker Discovery
Authors: Danilo Fliser, Jan Novak, Visith Thongboonkerd, A[Combining Grave Accent]ngel Argile[Combining Acute Accent]s, Vera Jankowski, Mark A. Girolami, Joachim Jankowski, Harald Mischak
Journal: Journal of the American Society of Nephrology (2007)

Noninvasive diagnosis of kidney diseases and assessment of the prognosis are still challenges in clinical nephrology. Definition of biomarkers on the basis of proteome analysis, especially of the urine, has advanced recently and may provide new tools to solve those challenges. This article highlights the most promising technological approaches toward deciphering the human proteome and applications of the knowledge in clinical nephrology, with emphasis on the urinary proteome. The data in the current literature indicate that although a thorough investigation of the entire urinary proteome is still a distant goal, clinical applications are already available. Progress in the analysis of human proteome in health and disease will depend more on the standardization of data and availability of suitable bioinformatics and software solutions than on new technological advances. It is predicted that proteomics will play an important role in clinical nephrology in the very near future and that this progress will require interactive dialogue and collaboration between clinicians and analytical specialists.
PMO-149 Tenofovir use in hepatitis B infection in pregnancy: Abstract PMO-149 Table 1
Authors: G Chakrabarty, S Clark, D Forton
Journal: Gut (2012)

<h3>Introduction</h3> Antenatal screening and immunoprophylaxis reduces the perinatal transmission of hepatitis B virus but vertical infection may occur with high level viraemia. Antiviral therapy during the 3rd trimester of pregnancy may reduce the incidence of intrauterine infection. Lamivudine treatment reduces vertical transmission if given with immunoglobulin and vaccination in mothers with viral loads &gt;10<sup>8</sup> IU/ml. There are no published trials for tenofovir in this context, although its use is supported by safety data from Antiretroviral Pregnancy Registryin USA (category B) with the added benefit of low viral resistance. Breastfeeding is not recommended as tenofovir is secreted in milk. Discontinuation of tenofovir after delivery carries the risk of hepatitis flares and liver decompensation. There are no guidelines for the use of antivirals in HBV-+ve pregnant women and treatment decisions are made on an individual basis. <h3>Methods</h3> We initiated tenofovir 245 mg in five HBV monoinfected women in the 3rd trimester to prevent vertical transmission. Demographic, virological and outcome data were collected. <h3>Results</h3> The patients were newly diagnosed during antenatal screening. They were all HBeAg+ve with high viral loads and normal ALT, presumed immunotolerant. All women wished to breastfeed and four were advised to stop tenofovir at delivery but one stopped 6 days before birth. 1 mother continued after delivery due to increased ALT during treatment with ultrasound evidence of liver disease. There were no reported adverse effects. During or at the end of treatment four patients had rises in ALT (&gt;1–2ULN) but no jaundice or hepatic decompensation. All the babies were born healthy and received immunoglobulin and vaccination. <h3>Conclusion</h3> This small series demonstrates the safety of tenofovir in the last trimester of pregnancy. Small increases in ALT were seen which could be due to pregnancy, the initiation or discontinuation of tenofovir. It is necessary to assess the stage of liver disease to guide the treatment strategy after birth, although this is not always feasible in pregnancy. The timing of tenofovir discontinuation is determined by breastfeeding. We recommended that breastfeeding should start 24 h after treatment cessation, although there is not an evidence base to support this. Long-term prospective studies are indicated to confirm efficacy, safety and to determine optimal discontinuation strategies in relation to breastfeeding. <h3>Competing interests</h3> None declared.
Body movements on the men’s competition mushroom: a three dimensional analysis of circular swings
Authors: G Grassi, M Turci, Y F Shirai, N Lovecchio, C Sforza, V F Ferrario
Journal: British Journal of Sports Medicine (2005)

Objectives: To develop a method for the three dimensional analysis of body movements and body positions during the performance of circular swings on the competition mushroom, an apparatus used by young gymnasts for pommel horse training. Methods: Five experienced male gymnasts, all of national level, performed three series of 10 circular swings on the competition mushroom. An optoelectronic instrument was used for the detection of the three dimensional movement of 13 body landmarks. From landmark trajectories, several technical measurements were obtained: diameters of ideal circles of ankles, hips, shoulders; deviation of the ankle diameters from circularity and from the horizontal plane; angle between the shoulder, hip, and ankle. The values were used for a quantitative assessment of performance of the five gymnasts. Results: During the exercise, each ankle should follow a nearly horizontal circular path (deviation from circularity ranged from 3.6% to 6%, deviation from horizontality was 9.4–19.7%), there should be an angle of about 180° at the hips (actual values 146–153°), and the shoulders should move as little as possible, and only in the lateral plane, without major anteroposterior movements (shoulder movement was 27–31% of ankle movement, hip movement was 16–20%). Conclusions: The method could help coaches and gymnasts to determine which parts of the body are not repeating a selected movement with sufficient accuracy and to quantify improvements made after a specific training programme.
Dose Escalation Methods in Phase I Cancer Clinical Trials
Authors: Christophe Le Tourneau, J. Jack Lee, Lillian L. Siu
Journal: JNCI Journal of the National Cancer Institute (2009)

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.
The detection of the nitrite reductase and NO-generating properties of haemoglobin by mitochondrial inhibition
Authors: Sruti Shiva, Tienush Rassaf, Rakesh P. Patel, Mark T. Gladwin
Journal: Cardiovascular Research (2010)

AimsNitrite (NO2−), now regarded as an endocrine reserve of nitric oxide (NO), is bioactivated by nitrite reductase enzymes to mediate physiological responses. In blood, haemoglobin (Hb) catalyses nitrite reduction through a reaction modulated by haem redox potential and oxygen saturation, resulting in maximal NO production around the Hb P50. Although physiological studies demonstrate that Hb-catalysed nitrite reduction mediates cyclic guanosine monophosphate (cGMP)-dependent vasodilation, the NO-scavenging effects of Hb raise questions about how NO generated from this reaction escapes the Hb molecule to signal at distant targets. Here, we characterize the NO-generating properties of Hb using the cGMP-independent and NO-dependent inhibition of mitochondrial cytochrome c oxidase.
Long-Term and Sustained COMP-Ang1 Induces Long-Lasting Vascular Enlargement and Enhanced Blood Flow
Authors: Chung-Hyun Cho, Kyung Eun Kim, Jonghoe Byun, Hyung-Suk Jang, Duk-Kyung Kim, Peter Baluk, Fabienne Baffert, Gyun Min Lee, Naoki Mochizuki, Jin Kim, Byeong Hwa Jeon, Donald M. McDonald, Gou Young Koh
Journal: Circulation Research (2005)

Vascular enlargement is a characteristic feature of angiopoietin-1 (Ang1)-induced changes in adult blood vessels. However, it is unknown whether tissues having Ang1-mediated vascular enlargement have more blood flow or whether the enlargement is reversible. We have recently created a soluble, stable and potent Ang1 variant, COMP-Ang1. In the present study, we investigated the effects of varied dose and duration of COMP-Ang1 on vascular enlargement and blood flow in the tracheal microvasculature of adult mice and explored a possible mechanism of long-lasting vascular enlargement. We found that COMP-Ang1 administered by adenoviral vector induced long-lasting vascular enlargement and increased tracheal blood flow. In contrast, short-term administration of COMP-Ang1 recombinant protein induced transient vascular enlargement that spontaneously reversed within a month. In both cases, the vascular enlargement resulted from endothelial proliferation. The COMP-Ang1–induced vascular remodeling is mediated mainly through Tie2 activation. Sustained overexpression of Tie2 could participate in the maintenance of vascular changes. Together, our findings indicate that sustained treatment with COMP-Ang1 can produce long-lasting vascular enlargement and increased blood flow.
Moderate Alcohol Intake and Cancer Incidence in Women
Authors: N. E. Allen, V. Beral, D. Casabonne, S. W. Kan, G. K. Reeves, A. Brown, J. Green
Journal: JNCI Journal of the National Cancer Institute (2009)

With the exception of breast cancer, little is known about the effect of moderate intakes of alcohol, or of particular types of alcohol, on cancer risk in women. A total of 1 280 296 middle-aged women in the United Kingdom enrolled in the Million Women Study were routinely followed for incident cancer. Cox regression models were used to calculate adjusted relative risks and 95% confidence intervals (CIs) for 21 site-specific cancers according to amount and type of alcoholic beverage consumed. All statistical tests were two-sided. A quarter of the cohort reported drinking no alcohol; 98% of drinkers consumed fewer than 21 drinks per week, with drinkers consuming an average of 10 g alcohol (1 drink) per day. During an average 7.2 years of follow-up per woman 68 775 invasive cancers occurred. Increasing alcohol consumption was associated with increased risks of cancers of the oral cavity and pharynx (increase per 10 g/d = 29%, 95% CI = 14% to 45%, Ptrend < .001), esophagus (22%, 95% CI = 8% to 38%, Ptrend = .002), larynx (44%, 95% CI = 10% to 88%, Ptrend = .008), rectum (10%, 95% CI = 2% to 18%, Ptrend = .02), liver (24%, 95% CI = 2% to 51%, Ptrend = .03), breast (12%, 95% CI = 9% to 14%, Ptrend < .001), and total cancer (6%, 95% CI = 4% to 7%, Ptrend < .001). The trends were similar in women who drank wine exclusively and other consumers of alcohol. For cancers of the upper aerodigestive tract, the alcohol-associated risk was confined to current smokers, with little or no effect of alcohol among never and past smokers ( Pheterogeneity < .001). Increasing levels of alcohol consumption were associated with a decreased risk of thyroid cancer ( Ptrend = .005), non–Hodgkin lymphoma ( Ptrend = .001), and renal cell carcinoma ( Ptrend = .03). Low to moderate alcohol consumption in women increases the risk of certain cancers. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the esophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75.
THE PSYCHIATRIC PATIENT AS HIS OWN HISTORIAN
Authors: JAMES A. KENNY, RONALD C. BOUNOUS
Journal: American Journal of Psychiatry (1961)

The social history questionnaire is not a substitute for, nor can it be favorably compared to history-taking in a personal interview. Yet we feel that it is a legitimate diagnostic instrument in certain situations. That is to say, the questionnaire is preferable to sparse information gathered in a hasty manner or to no history at all. The time it saves, the prime material it offers, its built-in supervisory features, and its therapeutic possibilities may counterbalance the impersonality and superficiality of a form. We are presenting our SASH (Self-Administered Social History) in the hope that others will do likewise, and that certain optimum history questionnaires and questions might be developed.
THE ORIGIN OF PLATELETS
Authors: E. Fidlar, E. T. Waters
Journal: The Journal of Experimental Medicine (1941)

1. In heart-lung preparations perfused with heparinized blood, clumping of platelets and a sharp fall in the platelet count occurred in the first 5 to 15 minutes after the external circuit was established. 2. In 10 such preparations surviving from 1 to 4 hours, only one showed a return of the platelet count to the level existing before operation. 3. When platelets were reduced in numbers before the blood was used for perfusion, the count tended to level off after a small recovery, if any. 4. An estimate of clumping showed it to bear an inverse relationship to the platelet recovery. 5. No satisfactory evidence of platelet production in the lungs has been obtained in these studies with heart-lung preparations. 6. The possibility of special factors which may influence platelet formation is discussed.