tbuckley/cabot-search huggingface dataset:
HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy
Authors: Gabriel M. Ortiz, Douglas F. Nixon, Alexandra Trkola, James Binley, Xia Jin, Sebastian Bonhoeffer, Peter J. Kuebler, Sean M. Donahoe, Marie-Ange Demoitie, William M. Kakimoto, Tom Ketas, Brian Clas, Jonas J. Heymann, Linqi Zhang, Yunzhen Cao, Arlene Hurley, John P. Moore, David D. Ho, Martin Markowitz
Journal: Journal of Clinical Investigation (1999)

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1–infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than 500 copies/mL in 2 subjects for more than 12 and more than 24 months, respectively, and in 1 subject for 4 months on 1 occasion. Three subjects failed to contain plasma viremia. Broad and strong HIV-1–specific immune responses were detected in subjects with prolonged suppression of viral replication. This longitudinal study suggests that containment of HIV-1 replication to low or undetectable levels after discontinuation of HAART is associated with strong virus-specific immune responses. Boosting of HIV-1–specific immune responses should be considered as an adjunctive treatment strategy for HIV-1–infected individuals on HAART.
A Systematic Evaluation of Mechanisms in Chronic Cough
Authors: IAN K. CARNEY, PETER G. GIBSON, KEITH MURREE-ALLEN, NICHOLAS SALTOS, LESLIE G. OLSON, MICHAEL J. HENSLEY
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of diverse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to a tertiary referral clinic with chronic cough were compared with a group of 20 asymptomatic adults. Measurements included histamine provocation testing with measurement of flow volume curves to determine inspiratory and expiratory airflow obstruction; hypertonic saline induced sputum for analysis of eosinophils, mast cells and lipid-laden macrophages; and a validated psychological symptom questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common causes of chronic cough. BHR occurred in seven patients (23%) and in no control subjects (p < 0.05). UAHR occurred in 40% of patients with cough and in four (20%) control subjects (p > 0.05). Eosinophils were present in the sputum of more patients with cough than control subjects (50% versus 19%; p < 0.05). High degrees of eosinophilia were present in six patients with cough, including three without BHR. No subject had significant lipid-laden macrophages. There was greater somatization in patients with chronic cough; ten subjects scored in the clinically significant range (p < 0.05). Abnormalities in one or more of these tests were 7.67-fold (95% CI 1.83–34.52) more likely to occur in cough patients than control subjects. We conclude that chronic cough is a nonspecific symptom that is associated with several apparently unrelated mechanisms. These include UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated as a single unifying mechanism. These findings emphasize the need to systematically evaluate several different causes of cough in patients who present with chronic cough.
Oral Administration of Recombinant Adeno-associated Virus-mediated Bone Morphogenetic Protein-7 Suppresses CCl4-induced Hepatic Fibrosis in Mice
Authors: Zhi-Ming Hao, Min Cai, Yi-Fei Lv, Yan-Hua Huang, Hong-Hong Li
Journal: Molecular Therapy (2012)

Fibrogenesis and hepatocyte degeneration are the main pathological processes in chronic liver diseases. Transforming growth factor-β1 (TGF-β1) is the key profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is a potent antagonist of TGF-β1 and an antifibrotic factor. In this study, we generated a recombinant adeno-associated virus carrying BMP-7 (AAV–BMP-7) and tested its ability to suppress carbon tetrachloride (CCl4)-induced hepatic fibrosis when orally administered to mice. Our results show that the ectopic expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV–BMP-7 administration led to the long-term elevation of serum BMP-7 concentrations and resulted in the drastic amelioration of CCl4-induced hepatic fibrosis in BALB/c mice. Immunostaining for α-smooth muscle actin (α-SMA) and desmin demonstrated that AAV–BMP-7 inhibited the activation of hepatic stellate cells (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7 promoted hepatocyte proliferation, as confirmed by an increase in the amount of proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that received AAV–BMP-7. Our results clearly indicate that BMP-7 is capable of inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest that oral AAV–BMP-7 could be developed into a safe, simple, and effective therapy for hepatic fibrosis. Fibrogenesis and hepatocyte degeneration are the main pathological processes in chronic liver diseases. Transforming growth factor-β1 (TGF-β1) is the key profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is a potent antagonist of TGF-β1 and an antifibrotic factor. In this study, we generated a recombinant adeno-associated virus carrying BMP-7 (AAV–BMP-7) and tested its ability to suppress carbon tetrachloride (CCl4)-induced hepatic fibrosis when orally administered to mice. Our results show that the ectopic expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV–BMP-7 administration led to the long-term elevation of serum BMP-7 concentrations and resulted in the drastic amelioration of CCl4-induced hepatic fibrosis in BALB/c mice. Immunostaining for α-smooth muscle actin (α-SMA) and desmin demonstrated that AAV–BMP-7 inhibited the activation of hepatic stellate cells (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7 promoted hepatocyte proliferation, as confirmed by an increase in the amount of proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that received AAV–BMP-7. Our results clearly indicate that BMP-7 is capable of inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest that oral AAV–BMP-7 could be developed into a safe, simple, and effective therapy for hepatic fibrosis.
Ureteral Injury During a Hip-Nailing Procedure
Authors: Roger Billig
Journal: JAMA (1976)

URETERAL injury has been well reviewed in the literature. The vast majority of such injuries occur during operations on other structures, especially during gynecologic procedures.<sup>1-3</sup>Ureteral injury secondary to blunt or penetrating trauma to the pelvis or abdomen is very rarely the only site of injury.<sup>1,4</sup> To our knowledge, injury to the ureter during a hip-nailing procedure has never been reported previously. <h3>Report of a Case</h3> A 25-year-old man with partial atrophy of his right lower extremity secondary to childhood poliomyelitis fell on the day of admission, Dec 18, 1974, fracturing the proximal head of his right femur. A Jewett hip nailing was carried out on the day after admission. During the procedure, it was thought that one of the standard guide wires was possibly passed into the pelvis. It was promptly removed. The procedure was continued without further incident. During the next 24 hours, the patient experienced
Indigent Consumptives in the Southwest—A Warning
Authors: George D. Troutman
Journal: JAMA (1913)

Indigent Consumptives in the Southwest\p=m-\AWarning To the Editor:\p=m-\Iwish that publicity be given to the fact that this community, which is famed as a health-resort in the dry zone of the Southwest, will not give financial assistance \p=m-\freehospitals or sanatorium service or transportation\p=m-\to the hundreds of indigent tuberculous persons who apply for aid each year.So many incurable patients arrive here with- out means of support, and yet with hope of climatic cure and remunerative employment, that I desire these full explanations be made:1.Such rainbow-chasing is a cruel hoax to perpetrate on a dying consumptive.2. Comfort and treatment are expensive and continuous.3. It is the rare exception, and growing rarer, that a tuber- culous person can obtain employment, no matter how great his ability.
Compression of the oesophagus by the aorta
Authors: I. K. R. McMillan, I. Hyde
Journal: Thorax (1969)

Compression of the lower dorsal oesophagus by the aorta in elderly women sufficient to cause dysphagia has not received the attention it deserves. It is not a rare condition. The reasons for its neglect are probably two-fold: (1) the degree of dysphagia is often only slight or moderate, and (2) misdiagnosis. Occasionally, the dysphagia is serious and a threat to life. The clinical and radiological features are here described and a rational operative treatment for the severe cases is proposed. Such operative intervention does not seem to have been described previously.
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment
Authors: Dennis M. Black, Ann V. Schwartz, Kristine E. Ensrud, Jane A. Cauley, Silvina Levis, Sara A. Quandt, Suzanne Satterfield, Robert B. Wallace, Douglas C. Bauer, Lisa Palermo, Lois E. Wehren, Antonio Lombardi, Arthur C. Santora, Steven R. Cummings, for the FLEX Research Group
Journal: JAMA (2006)

The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain.To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years.Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT).One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment.Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003).The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence.Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens.Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.clinicaltrials.gov Identifier: NCT 00398931.
Plasma Ketosteroids and Testosterone in Man: A Study of the Pituitary-testicular Axis*
Authors: Marvin A. Kirschner, Mortimer B. Lipsett, David R. Collins
Journal: Journal of Clinical Investigation (1965)

1The following trivial names have been used: testos- terone, 17p8-hydroxy-4-androsten-3-one; dehydroepiandros- terone, 3,8-hydroxy-5-androsten-3-one; androstenedione, 4-androsten-3,17-dione; androsterone, 3a-hydroxy-5a-androstan-17-one; etiocholanolone, 3a-hydroxy-5fi-androstan-17-one; epitestosterone, 17a-hydroxy-4-androsten-3one; epiandrosterone, 3f8-hydroxy-5a-androstan-17-one; cortisol, 1lfi-17a,21-trihydroxy-4-pregnen-3,20-dione.C"-labeled steroids were added, plasma was extracted, and the steroids were separated by thin-layer and paper chromatography.After acetylation and thin-layer chromatography, final purification was achieved with gasliquid chromatography The effluent was collected and the isotopes were counted.Materials.Testosterone-4-C" (SA, 22 mc per mmole) 2 and dehydroepiandrosterone-4-C1' (SA, 50 mc per mmole) 2 were chromatographed in the Bush system, Al, and on thin-layer silica gel before use.The final material had less than 2% impurity on the basis of gas-liquid chroma- tography.Specific activities were determined by liquid scintillation counting and gas-liquid chromatography.In general, the specific activities agreed closely with those given by the supplier.
Determining How Much Medical Care We Need
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1980)

Let's suppose you want to know how much specialized medical care — how many specialists and how many specialized diagnostic and therapeutic services — this country really needs.One way to approach this question would be to go to the experts and ask them to calculate the answers on the basis of the estimated prevalence and incidence of diseases and the kinds of personnel and services needed to provide the appropriate medical care. That is the approach taken, for example, in the recent report of the Graduate Medical Education National Advisory Committee (GMENAC), which used panels of consultant specialists in . . .
Executives with White Coats — The Work and World View of Managed-Care Medical Directors
Authors: T Bodenheimer, L Casalino
Journal: New England Journal of Medicine (1999)

During the past two decades, a new breed of physician leaders has emerged. These leaders — the medical directors of health plans, medical groups, and independent practice associations (IPAs) — exercise substantial influence over medical practice. Yet little is known about them. By which routes did they come to their jobs? What do they do when they arrive at work each day? What are their beliefs?In this report we describe the career paths of medical directors, classify the types of medical directors, and describe the varieties of work they do. We contrast the views of medical directors with the . . .
Giant fundic gland polyp mimicking a gastric malignancy
Authors: A. Winkler, T. Hinterleitner, C. Langner
Journal: Endoscopy (2007)

A 67-year-old man presented with nonspecific abdominal discomfort. Gastroscopy showed a polypoid mass carpeting the lesser curvature and large parts of the anterior wall of the gastric body (Figure [1] a). On endosonography the tumor was found to be partially cystic, with irregular thickening of the first three layers (Figure [1] b). Parts of the lesion were resected endoscopically. Histological examination revealed the typical features of a benign fundic gland polyp, with cystically dilated glands lined by flattened parietal cells, chief cells, and occasional mucinous cells; there was no nuclear atypia and no mitotic figures (Figure [1] c, d). A single low-grade tubular adenoma was found in the patient's sigmoid colon. His family history was unremarkable.
Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral <scp>l</scp> -Arginine in Patients With Heart Failure
Authors: Thomas S. Rector, Alan J. Bank, Kathleen A. Mullen, Linda K. Tschumperlin, Ronald Sih, Kamalesh Pillai, Spencer H. Kubo
Journal: Circulation (1996)

Background Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from l -arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral l -arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure. Methods and Results Fifteen subjects were given 6 weeks of oral l -arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral l -arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1±2.8 to 6.6±3.4 mL·min −1 ·dL −1 ( P &lt;.05). Furthermore, functional status was significantly better on l -arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390±91 versus 422±86 m, P &lt;.05) and lower scores on the Living With Heart Failure questionnaire (55±28 versus 42±26, P &lt;.05). Oral l -arginine also improved arterial compliance from 1.99±0.38 to 2.36±0.30 mL/mm Hg ( P &lt;.001) and reduced circulating levels of endothelin from 1.9±1.1 to 1.5±1.1 pmol/L ( P &lt;.05). Conclusions Supplemental oral l -arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral l -arginine and to identify mechanisms of action in patients with heart failure.
Venereal Disease Education
Authors: Philip G. Boysen
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I read with interest the recent lead EDITORIAL "Young Physicians' Knowledge of Venereal Disease" (220:1736, 1972). As a flight surgeon on active duty with the Navy, I share the authors' concern over the gravity of this problem. I have reservations, however, about the conclusion that reemphasis of venereal disease education in medical schools will solve the problem. I was undergoing an orientation course at approximately the same time that my colleagues were confronted with this test. I daresay I would have fared no better, despite being exposed to one full week devoted exclusively to didactic and clinical experience in venereology in medical school. The concept that a graduate of a medical school is primed with all the knowledge he will need to practice medicine for 40 years is in a deserving state of disrepute. This particular dilemma further repudiates that concept. In my present status I have
Abstract 654: High-throughput RNAi screening for the identification of genes that potentiate paclitaxel response in metastatic breast cancer
Authors: Meredith C. Henderson, Irma M. Gonzales, Shilpi Arora, Lourdes Peralta, Tanya H. Little, Ashish Choudhary, David O. Azorsa
Journal: Cancer Research (2010)

Abstract In the United States, metastatic breast cancer is currently the second leading cause of death in women after lung cancer and it has been estimated that over 400,000 women worldwide die from the disease each year. Two chemotherapeutic agents that have shown much promise in treatment of metastatic breast cancer are paclitaxel and docetaxel, both being members of a class of drugs known as taxanes. Although the current regimens in the treatment of metastatic breast cancer often include one of these taxanes, the overall response rate is between 30-60%, indicating that about half the patients that receive treatment for metastatic breast cancer do not respond. In order to improve paclitaxel response in breast cancer cells, we employed a functional genomics based approach, utilizing high-throughput RNAi (HT-RNAi) to identify genes that, when silenced, would sensitize breast cancer cells to paclitaxel. The HT-RNAi assay was developed to quantify the growth inhibition of MDA-MB-231 breast cancer cells transfected with siRNA and treated with an EC30 dose of paclitaxel. For screening, MDA-MB-231 cells were reverse-transfected with siRNA from a library targeting 7000 druggable genes (2 siRNA per gene). Twenty-four hours after siRNA transfection, an EC30 dose of paclitaxel was added and cell viability was assessed after 72 hours of drug exposure. The data was analysed using the B-score method. Following data analysis, we generated a list of “gene targets”, which upon silencing individually, lead to potentiation of paclitaxel in breast cancer cells. Validation of these genes will identify potential therapeutic targets for novel paclitaxel combinations in order to improve clinical efficacy. Furthermore, these findings demonstrate the effectiveness of using HT-RNAi as a tool for identifying sensitizing targets to chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 654.
The price of coffins: specious arguments by eminent doctors against the dangers of tobacco
Authors: P Cowen
Journal: BMJ (1999)

> One does not avert death by ignoring the price of coffins.
> 
> Ernest Bramah, Kailung Unrolled His Mat 

In June 1957 the BBC radio news reported on a white paper, prepared by Doll and Hill, which had been presented to parliament.1 The paper claimed that cigarette smoking appreciably increased a person's risk of developing lung cancer, with the incidence increasing in proportion to the number of cigarettes smoked. This news was published in a statement by the Medical Research Council,2 which referred to Doll and Hill's findings published in the BMJ and the Lancet . The minister of health at the time was asked in parliament what he intended to do about the findings His response was “nothing” (which was the case) and that it was up to the medical officers of health to act on this information as they saw fit.

#### Summary points

Good evidence shows that smoking causes lung cancer

The media's response to this information was initially resistant

Specious arguments were used to detract from the real issue, which confused the general public and lessened its concern

After 40 years there has been little change in smoking rates

Having smoked over 20 cigarettes a day for 11 years I was alarmed by this information and decided to stop immediately; I have not smoked since. Shortly after quitting I began to take an interest in the response to the white paper and was surprised by what I found. In general, newspaper articles reflected resistance to the findings—for example, the chairman of the Tobacco Workers Trade Union was reported in the tabloid press about 1960 as saying that cigarettes alone could not be blamed for lung cancer as no …
Transient Splenic Accumulation of Tc-99m HMDP Caused by Megaloblastic Anemia
Authors: MITSURU KOIZUMI, TAKEHIRO SUZUKI, SHUNJI TAKAHASHI, ETSURO OGATA
Journal: Clinical Nuclear Medicine (2000)

A case of transient splenic accumulation of the bone-seeking agent Tc-99m HMDP is reported. This effect was caused by transient megaloblastic anemia induced by 5-fluorouracil chemotherapy. The extent of splenic uptake reflected the development and severity of megaloblastic anemia. The mechanism of splenic accumulation is thought to be similar to transient iron deposition in the spleen by megaloblastic anemia.