tbuckley/cabot-search huggingface dataset:
Allogeneic Bone Marrow Transplantation for 144 Patients With Severe Aplastic Anemia
Authors: Mortimer M. Bortin
Journal: JAMA (1981)

Comprehensive data were reported to the International Bone Marrow Transplant Registry by 24 worldwide teams regarding 144 patients with severe aplastic anemia who were treated with HLA-identical, allogeneic bone marrow transplantation between 1975 and 1978. One hundred fourteen patients received one transplant and 30 received two. Sustained engraftment of donor marrow occurred on the first transplant attempt in 76% of the patients whose engraftment status could be evaluated. Moderate, severe, or lethal graft-vs-host disease (GVHD) occurred in 52% of the engrafted patients. The one-year survival rate for all patients was 44% (64/144). Among the one-year survivors, the primary disease was apparently cured in 90% and improved in 10%. Thus far, four patients died one to five years after transplant. Of the 60 patients currently alive, ten have chronic GVHD and the remainder are in good health. Multivariate analyses of the data disclosed a number of pretransplant factors associated with engraftment, GVHD, and one-year survival. The most important finding was that the use of male donors was preferable to female donors because of a higher rate of engraftment, less severe GVHD, and a higher one-year survival rate.
Effects of physical training on end-diastolic volume and myocardial performance of isolated rat hearts.
Authors: M M Bersohn, J Scheuer
Journal: Circulation Research (1977)

We studied the performance of ventricular muscle and cardiac function of hearts from rats conditioned by swimming (CH) and from sedentary rats (SH) in an isolated working heart apparatus modified to measure end-diastolic volume by dye dilution. Instantaneous aortic flow, left ventricular (LV) pressure and oxygen consumption were measured. Heart rate and mean aortic pressure were kept constant, and atrial filling pressure was varied from 5 to 20 cm H2O. Heart weights of SH and CH were equal and end-diastolic pressures and volumes were similar at all atrial pressures. However, ejection fraction, calculated circumferential fiber velocity, peak systolic pressure, peak aortic flow, cardiac output, and stroke work were all greater in CH than in SH, and the differences increased as atrial pressure was increased. Maximal negative dP/dt was greater in CH than SH at all preloads (P less than 0.001). Oxygen consumption of CH was increased in proportion to the increase in work. These results indicate that the improved pumping performance of CH is due to a change in ventricular muscle function. Faster relaxation is a prominent effect of physical training on the rat heart and may foster more complete filling at high heart rates.
Pituitary Apoplexy-Reply
Authors: David Fitz-Patrick
Journal: JAMA (1981)

<h3>In Reply.—</h3> We agree that CT has replaced PEG in the evaluation of suprasellar extension of pituitary tumors, and noted this in our article. The PEG was performed in case 1 because, at that time, CT was in its infancy, and we wished to confirm the CT findings. In case 2, an intraoperative PEG was performed as a guide to the neurosurgeon, but this is no longer done. We differ with Dr Raskind regarding the value of angiography. In our opinion, the CT scan shown in Fig 3 could equally well result from a giant carotid aneurysm as from a necrotic pituitary adenoma, and only angiography will differentiate the two conditions. We do not usually perform angiography in the preoperative examination of patients undergoing elective transsphenoidal removal of a microadenoma. However, in patients with larger adenomas, we usually do an angiogram to define precisely the course of the carotid arteries
Pit Latrines and Groundwater Contamination: Negative Impacts of a Popular Sanitation Method
Authors: Tanya Tillett
Journal: Environmental Health Perspectives (2013)

Negative Impacts of a Popular Sanitation MethodWorldwide an estimated 1.77 billion people use pit latrines as their primary mode of sanitation.With the prevalence of pit latrine use growing in developing countries, there is heightened concern about the negative impacts on drinking water.A new review assesses the known and measured environmental health impacts associated with groundwater contamination by pit latrines [EHP 121(5):521-530; http://dx.doi.org/10.
Abstract 4572: Frequent MLL3 frameshift mutations in microsatellite-deficient colorectal cancer
Authors: Yoshiyuki Watanabe, Ryan J. Castoro, Hyun Soo Kim, Brittany Kleb, Ritsuko Oikawa, Tetsuya Hiraishi, Saira S. Ahmed, Woonbok Chung, Mee-Yon Cho, Minoru Toyota, Fumio Itoh, Marcos R. H. Estecio, Lanlan Shen, Jaroslav Jelinek, Jean-Pierre J. Issa
Journal: Cancer Research (2012)

Abstract Background: MLL3 is a histone 3- lysine 4 methyltransferase with tumor-suppressor properties that belongs to a family of chromatin regulator genes potentially altered in neoplasia. Mutations in MLL3 were found in a whole genome analysis of colorectal cancer but have not been confirmed by a separate study. Methods &amp; Results: We analyzed mutations of the coding region and promoter methylation in MLL3 using 126 cases of colorectal cancer. We found two isoforms of MLL3 and DNA sequencing revealed frameshift and other mutations affecting both isoforms of MLL3 in colorectal cancer cell lines and 19 of 134 (14%) primary colorectal samples analyzed. Moreover, frameshift mutations were more common in cases with microsatellite instability (31%) both in CRC cell lines and primary tumors. The largest isoform of MLL3 is transcribed from a CpG island-associated promoter that has highly homology with a pseudo-gene on chromosome 22 (psiTPTE22). Using an assay which measured both loci simultaneously we found prominent age related methylation in normal colon (from 21% in individuals less than 25 years old to 56% in individuals older than 70, R=0.88, p&amp;lt;0.001) and frequent hypermethylation (83%) in both CRC cell lines and primary tumors. We next studied the two loci separately and found that age and cancer related methylation was solely a property of the pseudogene CpG island and that the MLL3 locus was unmethylated. Conclusions: We found that frameshift mutations of MLL3 in both CRC cells and primary tumor that were more common in cases with microsatellite instability. Moreover, we have shown that the CpG island-associated promoter of MLL3 gene has no DNA methylation in CRC cell lines but also primary tumors and normal colon, and this region is highly homologous to a pseudogene (psiTPTE22) that shows age-related DNA methylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4572. doi:1538-7445.AM2012-4572
Arsenic Thiolation and the Role of Sulfate-Reducing Bacteria from the Human Intestinal Tract
Authors: Sergio S.C. DC.Rubin, Pradeep Alava, Ivar Zekker, Gijs Du Laing, Tom Van de Wiele
Journal: Environmental Health Perspectives (2014)

Arsenic (As) toxicity is primarily based on its chemical speciation. Although inorganic and methylated As species are well characterized in terms of metabolism and formation in the human body, the origin of thiolated methylarsenicals is still unclear.We sought to determine whether sulfate-reducing bacteria (SRB) from the human gut are actively involved in the thiolation of monomethylarsonic acid (MMAV).We incubated human fecal and colon microbiota in a batch incubator and in a dynamic gut simulator with a dose of 0.5 mg MMAV in the absence or presence of sodium molybdate, an SRB inhibitor. We monitored the conversion of MMAV into monomethyl monothioarsonate (MMMTAV) and other As species by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry analysis. We monitored the sulfate-reducing activity of the SRB by measuring hydrogen sulfide (H2S) production. We used molecular analysis to determine the dominant species of SRB responsible for As thiolation.In the absence of sodium molybdate, the SRB activity-primarily derived from Desulfovibrio desulfuricans (piger)-was specifically and proportionally correlated (p < 0.01) to MMAV conversion into MMMTAV. Inactivating the SRB with molybdate did not result in MMAV thiolation; however, we observed that the microbiota from a dynamic gut simulator were capable of demethylating 4% of the incubated MMAV into arsenous acid (iAsIII), the trivalent and more toxic form of arsenic acid (iAsV).We found that SRB of human gastrointestinal origin, through their ability to produce H2S, were necessary and sufficient to induce As thiolation. The toxicological consequences of this microbial As speciation change are not yet clear. However, given the efficient epithelial absorption of thiolated methylarsenicals, we conclude that the gut microbiome-and SRB activity in particular-should be incorporated into toxicokinetic analysis carried out after As exposure.
No mean feet
Authors: Dinesh Singhal, Samiran Nundy
Journal: BMJ (2004)

Pramod Karan Sethi,the inventor of a revolutionary artificial foot, regrets that he has not been able to pass his idealism on to young doctors. He talks to Dinesh Singhal and Samiran Nundy 

It was pure chance that led Pramod Karan Sethi to take up orthopaedics. “In 1958 the Medical Council of India were to inspect Jaipur Medical College to see whether it was worthy of accreditation, but there was no department of orthopaedics. I—who was trained as a general surgeon and had recently returned from the United Kingdom—was ordered by the principal to start one,” Dr Sethi explains.

This act of expediency on the principal's part had more far reaching consequences thanhe could have envisaged, for Sethi went on to design a light, hard wearing, cheap artificial foot that transformed the lives of thousands of people in the subcontinent. As Sethi worked in the Rajasthan city of Jaipur, it became known as the Jaipur foot.

Sethi, a 76 year old who has devoted his life to helping disadvantaged people, believes that it was because he had not trained as an orthopaedic surgeon that helped him produce something that was genuinely new.

“I think this made me look at the subject …
Concomitant traumas influence prognosis in melanomas of the nail apparatus*
Authors: G. Bormann, W.C. Marsch, J. Haerting, P. Helmbold
Journal: British Journal of Dermatology (2006)

Background In nail apparatus melanomas (NAM), the role of standard melanoma prognostic factors is under discussion. The prognostic influence of traumas to the clinically apparent tumour has not been sufficiently examined. Objectives To estimate the influence of traumas against the background of standard prognostic factors on the course of NAM. Methods In 33 patients (20 women, 13 men, median age 65·0 years) with NAM (median tumour thickness 3·5 mm), we retrospectively examined a detailed history of trauma to the affected extremity at first presentation. Histological or other standard prognostic factors and follow‐up were studied prospectively using a standardized protocol. Results Of 33 patients, 21 had suffered injury to the clinically apparent melanoma primary between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy up to 3 months ahead of excision of the melanoma was not considered). Eight of these patients had undergone inadequate therapy procedures. In Kaplan–Meier analysis, trauma to the clinically apparent tumour and tumour thickness were found to be significant prognostic factors for recurrence‐free survival, and trauma to the clinically apparent tumour, Clark level and tumour thickness were significant prognosis predictors for overall survival. In Cox's proportional hazards model, trauma to the clinically apparent tumour was found to be a significant and independent risk factor with regard to overall survival (hazard ratio 5·39; P = 0·029). An influence of trauma on the primary pathogenesis of NAM could not be confirmed. Only three patients reported trauma prior to the onset of tumour. Conclusions From our data, trauma to the clinically apparent tumour might be a considerable risk factor in NAM. The diagnosis of NAM should be considered in lesions of the nail apparatus and further deterioration of the prognosis due to inadequate therapeutic attempts or injury to the NAM should be avoided.
Multi-camera system of the endoscopy: endoscopic mucosal resection for large gastric lesion using a novel 1-channel camera-hood
Authors: K. Kume, M. Yamasaki, I. Yoshikawa, M. Otsuki
Journal: Endoscopy (2007)

Endoscopic procedures, such as endoscopic mucosal resection (EMR) for large gastric lesions, are performed blindly [1] [2]. Precise snaring during EMR is important to carry en-block resection. However, this can be difficult to achieve in practice because it is impossible to perform snaring by complete observation. Although we can easily observe the proximal side of the lifting lesion, it is hard to see the distal side after injection of saline solution into the submucosa. Therefore, we developed a novel 1-channel camera-hood, which allows an observation of the distal side of the lesion during snaring in EMR procedures.
Control of Thyrotropin Secretion in Man
Authors: Jerome M. Hershman, James A. Pittman
Journal: New England Journal of Medicine (1971)

ADVANCES in methodology have largely been responsible for the newer data on thyrotropin (TSH) secretion by the human pituitary gland. These advances are the radioimmunoassay of human TSH and the discovery of the structure of thyrotropin-releasing factor (TRF) that has led to its synthesis, the first hypothalamic neurohormone to be synthesized. Our aims are to review the recent progress in understanding the regulation of the pituitary secretion of thyrotropin in man and point out its clinical importance. In addition, we discuss the development of tests of the reserve capacity of the gland to secrete TSH, with emphasis on the clinical . . .
Quo vadis collateral blood flow? A commentary on a highly cited paper
Authors: W Schaper
Journal: Cardiovascular Research (2000)

This text is a commentary on the highly cited paper by Maxwell-Hearse-Yellon describing the amount of collateral blood flow in several species of mammals after coronary artery occlusion. The measurement of collateral blood flow, an academic exercise in previous times because of its invariance and the futility of changing the degree of adaptation under chronic conditions, has reached new importance because collateral vessel growth (presently called arteriogenesis) can now be manipulated with growth factors, their genes or peptides. The early successes and failures are discussed and a plea is made for the rigorous application of goldstandard methods (like in the Maxwell-Hearse-Yellon paper) to avoid disappointments in the new science of 'therapeutic angiogenesis'.
A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer
Authors: David R. Spigel, John D. Hainsworth, Dianna L. Shipley, Thomas J. Ervin, Peter C. Kohler, Eric T. Lubiner, James D. Peyton, David M. Waterhouse, Howard A. Burris, F. Anthony Greco
Journal: Journal of Thoracic Oncology (2011)
Platelet kinetics in congenital heart disease
Authors: A M. PETERS, A. ROZKOVEC, R N BELL, K. A HALLIDIE-SMITH, J. F GOODWIN, J P. LAVENDER
Journal: Cardiovascular Research (1982)

The survival of 111indium labelled platelets has been determined in a series of 47 subjects comprising nine with cyanotic congenital disease (Eisenmenger's syndrome), seven with congenital heart disease associated with left to right shunts, six with primary pulmonary hypertension, six with peripheral vascular disease, 11 with cardiac disorder associated with low cardiac output and eight normal volunteers. Compared with the value in the normals of 9.5 days, mean survival was significantly shortened in those with Eisenmenger's syndrome (8.4 days) and with peripheral vascular disease (8.5 days). It was normal in patients with left to right shunts (9.5 days). Gamma camera imaging in selected patients failed to reveal any abnormal sites of deposition of labelled platelets except in one patient with peripheral vascular disease who had bilateral abnormal activity in his lower limbs and a shortened platelet survival (8.0 days). From theoretical considerations, it was concluded that the reduction in platelet survival in Eisenmenger's syndrome was such that, had it been the result of pulmonary intravascular platelet deposition, abnormal activity should have been visible on chest scanning with the gamma camera. The absence of scintigraphic evidence of abnormal platelet deposition in the lungs of these patients, combined with the linear configuration of their platelet survival curves, suggests that the accelerated platelet destruction is in the reticuloendothelial (RE) system rather than intravascular. Indirect evidence in favour of increased RE destruction of platelets in Eisenmenger's syndrome was the finding of an approximate doubling of intrasplenic platelet transit time, indicating abnormal platelet pooling within the spleen.
Drugs for Status Epilepticus
Authors: J. W. Norris, M. J. Parsonage
Journal: BMJ (1967)

MMCLJOURNAL 45 help still further.To reduce our aid to these countries, who are incomparably poorer than our own, owing to our temporary financial difficulties seems both short-sighted and inhumane.Repeatedly 1 asked myself whether we were giving postgraduates from the East the training they really need.Even though many of them had passed postgraduate diplomas I suspect that they felt inadequately prepared for these vast problems of malnutrition, infection, and overpopulation.We need to reconsider both the content of postgraduate education given to doctors from these coun- tries while they are over here and to see how we can give them much more effective support after they return home.-Iam, etc.,
Foam Stability Predictions of Respiratory Distress in Infants Delivered by Repeat Elective Cesarean Section
Authors: Richard M. Cowett, William Oh
Journal: New England Journal of Medicine (1976)

Amniocentesis for assessment of lung maturity has been recommended before delivery by elective repeat cesarean section because respiratory distress may occur in infants delivered in this manner. To test this hypothesis, foam stability tests of amniotic fluid (84 cases) or gastric aspirate (25 cases) were used as interchangeable indexes of pulmonary maturity in 109 infants born by repeat elective cesarean section. Of the 81 infants with a positive foam stability test, only 2.5 per cent had transient respiratory distress, but 8.3 per cent with intermediate or negative foam stability tests had respiratory difficulty (P less than 0.025). The results support recommendations that fetal lung maturity should be assessed before elective repeat cesarean section to minimize the risk of respiratory morbidity.
515. Overlapping Adeno-Associated Viral (AAV) Vector Mediated Gene Transfer Is Dependent on Viral Serotype and the Transgene Sequence in Skeletal Muscle
Authors: Arkasubhra Ghosh, Yongping Yue, Dongsheng Duan
Journal: Molecular Therapy (2005)

The small packaging capacity is one of the major hurdles for adeno-associated virus (AAV)-mediated gene therapy. The overlapping approach has been developed recently to expand the AAV packaging capacity (Duan et al, Mol. Ther. 4:383, 2001; Halbert et al, Nat. Biotechnol.20:697, 2002). In this approach, a large gene is split into two partially overlapping fragments and separately packaged into two AAV vectors, including the upstream (carrying the 5'-end of the gene) and the downstream (carrying the 3'-end of the gene) vectors. Transgene expression is achieved after homologous recombination of the overlapping region between the upstream and the downstream vectors in co-infected cells. Despite the promising proof-of-principle results in the lung with AAV-6 alkaline phosphatase (AP) overlapping vectors, the transduction efficiency in skeletal muscle has been very disappointing. With AAV-2 LacZ overlapping vectors, the efficiency is only 0.37% of that from an intact AAV-2 LacZ vector. This level of expression is far from sufficient to treat muscular dystrophy. In this study, we examined two potential rate-limiting factors in the overlapping approach, including AAV serotype and the transgene sequence. Previous studies suggest that AAV transduction in muscle is influenced by viral serotype. AAV-6 mediates much higher gene expression than AAV-2 in muscle. To test whether AAV-6 can improve overlapping vector-mediated gene transfer in muscle, we delivered a total of 1 |[times]| 10e9 viral genome particles of LacZ overlapping vectors (AAV-2 or AAV-6; 5 |[times]| 10e8 particles of each vector including the upstream and the downstream vectors) to the anterior tibialis (TA) muscle of 6-week-old BL10 mice. As a control, we also delivered 5 |[times]| 10e8 particles of the intact AAV LacZ vector to the contra-lateral TA muscle. Transduction efficiency was quantified at 6 weeks later by scoring the percentage of LacZ positive myofibers. Consistent with previous reports, less than 0.03% of myofibers were transduced by AAV-2 overlapping vectors. However, AAV-6 overlapping vectors yielded 35.2 |[plusmn]| 5.7% transduction. This equals 42.25% of that of the transduction efficiency from an intact AAV-6 LacZ vector. To determine whether the transgene sequence effects the transduction efficiency, we compared AAV-6 LacZ and AAV-6 AP overlapping vectors. Surprisingly, the transduction efficiency of AP overlapping vectors (80.4 |[plusmn]| 2.8%) reached that of the intact AP vector (84.1 |[plusmn]| 1.9%). In summary, our findings suggest that AAV-6 overlapping vectors represent a promising approach to deliver certain larger therapeutic genes for muscular dystrophy gene therapy.
Metformin As an Addition to Conventional Chemotherapy in Breast Cancer
Authors: Tal Grenader, Anthony Goldberg, Linda Shavit
Journal: Journal of Clinical Oncology (2009)

metformin inbreast cancer may be related to activation of adenosine monophosphate‐activated protein kinase, which may ultimately result in a rapid inhibition of cellular protein synthesis and growth of tumor cells. We suggest, however, that additional mechanisms may play a part. It is a well-accepted fact that chronic inflammation is a major contributory factor to cancer development and progression, and elevated levels of various nonspecific markers of inflammation in the serum have been shown to be associated with poor survival in a number of different cancers. Pierce et al 3 have recently assessed the relationship between circulating levels of C-reactive protein and serum amyloid A and breast cancer survival. They showed that raised levels of these inflammatory markers were associated with a significantly reduced overall survival and a trend toward a reduced diseasefreesurvival.Patientswithtype2diabetesmellitustendtohavehigher C-reactive protein concentrations than those without it, suggesting that inflammation may contribute to the higher risk of breast cancer and worse prognosis of malignant disease in these patients. 4 Thereisevidencetosuggestthatmetforminhasapositiveimpact on inflammation and endothelial dysfunction. Metformin was compared with another oral hypoglycaemic agent, repaglinide, in nonobese patients with type 2 diabetes and shown to be more effective in
P2-003: Increased vascular-endothelial growth factor A (VEGF-A) expression and response to angiogenesis inhibitor erlotinib in non-small-cell lung cancer (NSCLC) - Hint for a new predictive marker?
Authors: Wolfgang M. Brueckl, Ralph M. Wirtz, Anja Schoeberl, Samuel Murray, Eckhart G. Hahn, Gunther H. Wiest
Journal: Journal of Thoracic Oncology (2007)