tbuckley/cabot-search huggingface dataset:
Expired-Air Acetone in Diabetes Mellitus
Authors: Richard D. Stewart, Edward A. Boettner
Journal: New England Journal of Medicine (1964)

SINCE Lerch suggested in 1874 that the characteristic odor in a diabetic patient's breath was acetone several methods for measuring this compound in breath have been devised.1 2 3 4 5 In the small series of diabetic patients studied with these methods the impression has been that the concentration of acetone in the breath is a reliable index of the degree of ketonemia and, therefore, should be of clinical usefulness. However, measurements of breath acetone have not been used clinically because the proposed analytical methods have lacked one or more of the following features essential to a "practical" laboratory test: speed and simplicity of . . .
Regression of Neuroblastoma IV-S: A Genetic Hypothesis
Authors: Alfred G. Knudson, Anna T. Meadows
Journal: New England Journal of Medicine (1980)

Neuroblastoma is the classic tumor that illustrates the phenomenon of spontaneous regression. The most dramatic cases of regression occur in those infants who have disseminated disease involving liver, skin, or bone marrow. This clinical entity has been classified as a special form of disseminated neuroblastoma, Stage IV-S, to distinguish it from the more usual disseminated form,1 , 2 Stage IV. Recognition of Stage IV-S has stimulated great interest not only among clinicians, who now usually use less intensive therapy, but also among cancer biologists, who believe it can teach us about the natural history of cancer and suggest new means for modifying . . .
Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin
Authors: Sip Dinkla, Bram van Cranenbroek, Wouter A. van der Heijden, Xuehui He, Rike Wallbrecher, Ingrid E. Dumitriu, André J. van der Ven, Giel J. C. G. M. Bosman, Hans J. P. M. Koenen, Irma Joosten
Journal: Blood (2016)
Methyldopa Inhibition of Suppressor-Lymphocyte Function
Authors: Howard H. Kirtland, Daniel N. Mohler, David A. Horwitz
Journal: New England Journal of Medicine (1980)

To test the hypothesis that methyldopa induces red-cell autoantibodies by inhibiting the activity of suppressor lymphocytes, we studied its effect on several immune functions. Methyldopa inhibited T-lymphocyte suppression of IgG production by peripheral-blood mononuclear cells stimulated by pokeweed mitogens. This effect occurred in isolated T cells incubated with methyldopa and in T cells obtained from patients taking methyldopa. In addition, the drug caused a 30 to 80 per cent reduction in the proliferative response of peripheral-blood mononuclear cells to mitogens in vitro, and this reduction primarily involved the activation of T lymphocytes. Methyldopa also caused a persistent elevation of intracellular lymphocyte cyclic AMP in vitro and in vivo. We postulate that methyldopa alters the immune system by causing a persistent increase in lymphocyte cyclic AMP, which inhibits suppressor T-cell function. These effects may lead to unregulated autoantibody production by B cells in some patients. (N Engl J Med. 1980; 302:825–32.)
An Overview of Research and Evaluation Designs for Dissemination and Implementation
Authors: C. Hendricks Brown, Geoffrey Curran, Lawrence A. Palinkas, Gregory A. Aarons, Kenneth B. Wells, Loretta Jones, Linda M. Collins, Naihua Duan, Brian S. Mittman, Andrea Wallace, Rachel G. Tabak, Lori Ducharme, David A. Chambers, Gila Neta, Tisha Wiley, John Landsverk, Ken Cheung, Gracelyn Cruden
Journal: Annual Review of Public Health (2017)

The wide variety of dissemination and implementation designs now being used to evaluate and improve health systems and outcomes warrants review of the scope, features, and limitations of these designs. This article is one product of a design workgroup that was formed in 2013 by the National Institutes of Health to address dissemination and implementation research, and whose members represented diverse methodologic backgrounds, content focus areas, and health sectors. These experts integrated their collective knowledge on dissemination and implementation designs with searches of published evaluations strategies. This article emphasizes randomized and nonrandomized designs for the traditional translational research continuum or pipeline, which builds on existing efficacy and effectiveness trials to examine how one or more evidence-based clinical/prevention interventions are adopted, scaled up, and sustained in community or service delivery systems. We also mention other designs, including hybrid designs that combine effectiveness and implementation research, quality improvement designs for local knowledge, and designs that use simulation modeling.
Suppressive Therapy with Levothyroxine for Solitary Thyroid Nodules
Authors: Hossein Gharib, E. Meredith James, J. William Charboneau, James M. Naessens, Kenneth P. Offord, Colum A. Gorman
Journal: New England Journal of Medicine (1987)

Thyroid nodules are present in up to 50 percent of adults in the fifth decade of life. Patients are often treated with thyroxine in order to reduce the size of the nodule, but the efficacy of thyrotropin-suppressive therapy with thyroxine remains uncertain. In this study, 53 patients with a colloid solitary thyroid nodule confirmed by biopsy were randomly assigned in a double-blind manner to receive placebo (n = 25) or levothyroxine (n = 28) for six months. Before treatment, pertechnetate-99m thyroid scanning showed that 22 percent of the nodules were functional, 25 percent hypofunctional, and 53 percent nonfunctional. High-resolution (10-MHz) sonography was used to measure the size of the nodules before and after treatment. Suppression of thyrotropin release was confirmed in the levothyroxine-treated group by the administration of thyrotropin-releasing hormone; thyrotropin release was normal in the placebo group. Six months of therapy did not significantly decrease the diameter or volume of the nodules in the levothyroxine group as compared with the placebo group. We conclude that the efficacy of levothyroxine therapy in reducing the size of colloid thyroid nodules is not apparent within six months, despite effective suppression of thyrotropin.
Synergistic Combinations of Penicillins in the Treatment of Bacteriuria
Authors: Leon D. Sabath, Harvey A. Elder, Charles E. McCall, Maxwell Finland
Journal: New England Journal of Medicine (1967)

MOST bacteria that are highly resistant to benzylpenicillin produce penicillinases.1 2 3 4 Large numbers of bacterial cells of many strains, even some considered to be highly resistant to penicillins and cephalosporins, can be killed in the presence of moderate concentrations of these antibiotics, and the survivors proliferate only after most or all of the antibiotic has been destroyed by the enzymes.2 , 4 5 6 Except for a few unusual isolates,7 penicillinase-producing staphylococci owe their penicillin resistance completely to penicillinase (β-lactamase). There is considerable evidence that β-lactamases are also important for the resistance of many strains of gram-negative bacilli to penicillins4 5 6 , 8 and cephalosporins,5 , 6 but the precise . . .
Intraerythrocytic Adaptation to Anemia
Authors: J. Torrance, P. Jacobs, A. Restrepo, J. Eschbach, C. Lenfant, C. A. Finch
Journal: New England Journal of Medicine (1970)

The role of erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of hemoglobin oxygen in anemia was investigated. Measurements of 2,3-DPG and of oxygen dissociation (P50) were carried out on 57 normal subjects and 114 subjects with anemia. Twenty normal nonsmoking males had a mean hemoglobin of 15.3 g per 100 ml, a mean DPG of 4.83 mM and a mean P50 of 27.1 mm of mercury. Twenty normal nonsmoking females had a mean hemoglobin lower by 2.6 g per 100 ml, a DPG higher by 0.5 mM and a P50 increased by 0.4 mm of mercury DPG. P50 rose progressively with decreasing hemoglobin concentrations. For each gram of hemoglobin fall, there was a DPG increase of about 0.23 mM and a P50 increase of about 0.30 mm of mercury. Increases in adenosine triphosphate also occurred but, because of the smaller amount involved, had less effect on the oxygen dissociation curve. A rise in inorganic phosphate level had no demonstrable effect, but in vivo pH changes appear of considerable importance. It was calculated that DPG-induced changes in hemoglobin affinity for oxygen may compensate for up to half the oxygen deficit in anemia.
Blood donation
Authors: E A. E Robinson
Journal: BMJ (1996)

least, more than one symptom could be scored and perhaps more attention could be paid to the patients' experience of their illness,' including how they explain their illness and its course, what effect it has, how they feel about it, and what they expect of treatment (this is relatively easily done in an n of 1 trial).The n of 1 trial could indeed be used more in everyday clinical practice with good instruments, generic diaries, and a patient centred approach.
Does neoadjuvant chemotherapy in operable breast cancer increase breast conservation?
Authors: N. M. Abd El-Bary, A. F. El-Kased, H. Aiad
Journal: Journal of Clinical Oncology (2008)

11572 Background: The role of adjuvant chemotherapy in breast cancer is well established. Likewise the role of neoadjuvant chemotherapy in locally advanced breast cancer is well established. The use of neoadjuvant chemotherapy in operable breast cancer has only recently become of interest to researchers. Methods: This study included 34 patients of operable breast cancer who were given 4 cycles of neoadjuvant chemotherapy in the form of FEC-100 then subjected to surgery. Surgery done was either breast-conserving surgery (BCS) or modified radical mastectomy. All surgical specimens were studied pathologically for chemotherapy effect. Results: An overall objective response was observed in 70.6% of the patients. Seven patients (20.6%) experienced a clinical complete response (cCR), seventeen patients (50.0%) had partial response, nine patients (26.5%) had no change of their disease, and only one patient had disease progression. Of the seven patients who had a cCR, only four patients (11.8%) had pathologic complete response (pCR), while pCR for the whole group was14.7 %( 5/34). Tumour size of more than 2 cm was observed in 28 patients (82.4%) at time of presentation, while tumor size of 2 cm or less was seen in 6 patients (17.6%) only. After completion of the course of chemotherapy, twenty-three patients (67.6%) were observed to have tumors of 2 cm or less that allowed for less extensive resections. Twenty-three patients underwent breast-conserving surgery (67.6%) while modified radical mastectomy was performed in 11 patients (32.4%). Conclusions: The use of neoadjuvant chemotherapy in operable breast cancer in this study was associated with tumour and axillary downstaging which increased the proportion of cases undergoing breast conservation, with acceptable side effects and reasonable cost. During the limited follow-up period of this study, no locoregional recurrences were recorded and one distant treatment failure was recorded. Its impact -if any- on overall or disease-free survival was not addressed in this study. Larger multicenter randomized studies with long follow-up periods are needed to compare the overall and disease-free survival benefit of this treatment modality, especially in different subtype stratified by pathologic response. No significant financial relationships to disclose.
A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients
Authors: Cinzia Pellegrini, Anna Dodero, Annalisa Chiappella, Federico Monaco, Debora Degl’Innocenti, Flavia Salvi, Umberto Vitolo, Lisa Argnani, Paolo Corradini, Pier Luigi Zinzani
Journal: Journal of Hematology & Oncology (2016)

There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %. A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed/refractory PTCL, looking for a potential synergistic effect of the two drugs. GEMRO regimen contemplates an induction with romidepsin plus gemcitabine for six 28-day cycles followed by maintenance with romidepsin for patients in at least partial remission. The primary endpoint was the overall response rate (ORR); secondary endpoints were survival, duration of response, and safety of the regimen. The ORR was 30 % (6/20) with 15 % (3) complete response (CR) rate. Two-year overall survival was 50 % and progression-free survival 11.2 %. Grade ≥3 adverse events were represented by thrombocytopenia (60 %), neutropenia (50 %), and anemia (20 %). Two patients are still in CR with median response duration of 18 months. The majority of non-hematological toxicities were mild and transient. No treatment-related death occurred and no toxicity led to treatment interruption. GEMRO combination regimen shows efficacy data similar to those of single-agent romidepsin with additional hematologic toxicities. Synergy observed in preclinical phase did not turn into ability to improve clinical outcomes. The trial was registered under EudraCT 2012-001404-38; ClinicalTrials.gov number, NCT01822886 .
Parathormone-Like Effect of Magnesium Replenishment in Steatorrhea
Authors: Francis P. Muldowney, T. J. McKenna, L. H. Kyle, R. Freaney, M. Swan
Journal: New England Journal of Medicine (1970)

Five of nine patients with intestinal malabsorption had tetany associated with hypomagnesemia, hypocalcemia and absence of demonstrable bone disease. Apparent failure of parathyroid response was suggested by normal or low values for serum alkaline phosphatase and renal phosphate clearance. Intramuscular magnesium therapy abolished tetany in all. In two subjects with severe magnesium depletion there was a coincident rise in serum calcium, phosphate clearance and (in one case) alkaline phosphatase. Infusion of parathyroid extract in the magnesium-depleted state resulted in increased phosphaturia but without a rise in serum calcium. After magnesium repletion, both phosphaturic and calcemic effects were seen. The results are consistent either with failure of parathormone secretion during magnesium depletion or with a reversible resistance of bone to parathormone action.
Exposure by Desialylation of Myeloid Antigens on Acute Lymphoblastic Leukemia Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hannes Stockinger, Otto Majdic, Kristof Liszka, Werner Aberer, Peter Bettelheim, Dieter Lutz, Walter Knapp
 7
Journal: JNCI Journal of the National Cancer Institute (1984)

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.
Hypogammaglobulinemia with Thymoma and Probable Pulmonary Infection with Cytomegalovirus
Authors: Ralph F. Jacox, Edward S. Mongan, James B. Hanshaw, John P. Leddy
Journal: New England Journal of Medicine (1964)

ADULT patients with a thymic tumor or with hypogammaglobulinemia are sufficiently unusual that a co-existence of these two entities in the same patient is apt to be more than a chance circumstance. In the 6 cases of thymic tumor and hypogammaglobulinemia reported in the medical literature1 2 3 4 5 6 there is no clue to whether any relation may exist between these two pathologic entities.The present report describes a seventh case observed in an adult male in whom, after a surgical removal of a large thymoma, increasingly severe respiratory symptoms developed. Several years later the patient was found to have a significant decrease . . .
Transient Global Amnesia and a Father's Worst Nightmare
Authors: Mark A. Marinella
Journal: New England Journal of Medicine (2004)

To the Editor: Severe emotional stress can lead to a myriad of somatic or neurologic problems, including transient global amnesia, a syndrome of retrograde and anterograde memory loss without focal neurologic disturbances.1 I report the case of a healthy man who presented with transient, profound anterograde and retrograde amnesia that was precipitated by a disturbing dream. A healthy 61-year-old man was brought to the emergency department by his wife after she noticed that he was forgetful of the previous evening's activities and was unable to form new memories during the subsequent day. The patient repeated the same questions and could . . .
Bacteriology of the Bedside Carafe
Authors: Carl W. Walter, A. Daniel Rubenstein, Ruth B. Kundsin, Mary A. Shilkret
Journal: New England Journal of Medicine (1958)

PATIENTS' complaints of unpalatable bedside water called attention to the potential hazard of bedside drinking water as an unappreciated vehicle in crossinfection in hospitals. Inspection of patients' water carafes in several hospitals revealed turbid, malodorous water in a majority of cases.This finding stimulated the bacteriologic examination of the water carafes in 24 Boston hospitals, excluding those operated by the Commonwealth of Massachusetts and the United States Government. Cultures were taken during July and August, 1957. The density of coliforms was found higher than United States Public Health Service standards for drinking water. High density of staphylococci was also demonstrated. . . .
Young adults with leukemia in the United States: Lack of clinical trial participation and mortality reduction during the last decade
Authors: A. Bleyer, M. Montello, T. Budd
Journal: Journal of Clinical Oncology (2004)

6623 Background: Young adults with cancer have been found to have had less survival prolongation and mortality rate reduction than either younger or older patients (Proc. ASCO 21: 389a, 2002). We attempted to determine if this observation applied to young adults with leukemia and if so, why. Methods: National leukemia mortality rates during 1990–2000 were obtained from the National Center for Health Statistics. The incidence of leukemia during 1993–1999 was obtained in 4,214 1–44 year-olds (yo) from the U.S. SEER program (courtesy of L. Ries). To estimate national progress in reducing the mortality rate from leukemia relative to changes in its incidence, a relative survival rate index (RSR) was derived from the ratio of the mortality rate to incidence: 1 –[mortality rate:incidence]. National leukemia trial data were obtained on 14,087 <45 yo on cooperative group treatment trials during 1997–2002. Results: Above age 15, the clinical trial participation and survival rates co-declined precipitously for leukemia of all types, for acute lymphoblastic leukemia (ALL) and for acute myeloid leukemia (AML). Compared with <15 yo, 20–44 yo accrued to national treatment trials at 91–96%, 96–99%, and 61–82% lower rates, respectively, for all leukemia (Table), ALL and AML. For all leukemia, the RSR was 33–37% lower among 15–44 yo than in 1–15 yo (Table). For ALL, the RSR was 45–69% lower among 20–44 yo than among 1–15 yo. Corresponding values for AML were 35–46%. The RSR was significantly correlated with the national trial accruals: p < .0001, .001 and .01 for all leukemia, ALL and AML, respectively. Conclusions: A relative lack of progress in improving the outcome of young adults with leukemia appears to be due to their underrepresentation on clinical trials. Reversing the deficit will require broad support and collaboration to increase clinical trial availability, access, and participation. No significant financial relationships to disclose.
Touch-Perception Thresholds in Blind Diabetic Subjects in Relation to the Reading of Braille Type
Authors: R. W. Heinrichs, J. A. Moorhouse
Journal: New England Journal of Medicine (1969)

Many diabetic blind persons experience difficulty in reading Braille. This contrasts with clinical experience that diabetic neuropathy does not affect the hands. Accordingly, touch-perception thresholds were measured in 10 healthy seeing, 10 nondiabetic blind and 10 diabetic blind subjects. There were no differences in the thresholds for light touch, light contact vibration and two-point discrimination between the seeing and the nondiabetic blind subjects. In all the diabetic blind subjects the perception threshold for each of these modalities was increased. In two the abnormalities reached the level of awareness. Since the distance between the points in English Braille type is 2.2 mm, the difficulty of the diabetic subjects in reading Braille is probably related to an inability to perceive the individual points clearly. In the nondiabetic subjects the mean threshold for two-point discrimination was 1.6 mm whereas in the diabetic blind subjects it was 2.5 mm.
PWE-287 Long term outcomes after biological mesh reconstruction of the pelvic floor following extra-levator abdominoperineal excision of rectum (APER)
Authors: A Bhalla, O Peacock, H Javanmard-emamghissi, S Tou, N Hurst, W Speake, G Tierney, J Lund
Journal: Gut (2015)

<h3>Introduction</h3> Extra-levator abdominoperineal excision of the rectum (ELAPER) leaves a large pelvic floor defect requiring reconstruction. Our previous work has shown the benefits of biomesh repair over other techniques in the short term. The aim of this study is to determine long term outcomes of biological mesh pelvic floor reconstruction following ELAPER. <h3>Method</h3> Prospective data was collected for consecutive patients having ELAPER for low rectal cancer at a single UK institution between October 2008 and March 2013. The perineum was reconstructed using a biological mesh (Surgisis® Biodesign™, Cook Medical). Short and long-term outcomes were evaluated and the pelvis clinically assessed for herniation, and computed tomography scans reviewed by a specialist gastrointestinal radiologist for disease recurrence. <h3>Results</h3> Thirty-four patients (27 male, median age 62 years (range 40–72)) were included. Median operative time was 248 mins (range 120–340) with a median length of hospital stay of 9 days (range 4–20). Median length of follow-up was 32 months (range 21–64). Complications included three superficial perineal wound problems requiring surgery. No biological mesh weas removed and no further procedures were required. No perineal hernias have been detected. Local recurrence occurred in three patients (2 R1 and 1 R0 resection) and distant metastases in six. There was no 90-day mortality and 13% of patients died by the end of this study period. <h3>Conclusion</h3> Reduced incidence of long term complications, including low perineal hernia rates demonstrates that pelvic floor reconstruction with a biological mesh following ELAPER without the additional use of myocutaneous flaps is both safe and feasible. <h3>Disclosure of interest</h3> None Declared.