tbuckley/cabot-search huggingface dataset:
Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes
Authors: Despoina Vasilakou, Thomas Karagiannis, Eleni Athanasiadou, Maria Mainou, Aris Liakos, Eleni Bekiari, Maria Sarigianni, David R. Matthews, Apostolos Tsapas
Journal: Annals of Internal Medicine (2013)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs.To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes.MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature.Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes.Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control.Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods.Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear.None.
Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes
Authors: D E Jones, J V Metcalf, J D Collier, M F Bassendine, O F James
Journal: Hepatology (1997)

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their confounding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. Fourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P &lt; .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared with 5 of 11 (45.5%, P &lt; .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC followed-up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo prognostic model over-predicted survival. Whereas it is a relatively rare complication of cirrhotic PBC in women, HCC is a relatively common cause of death in male PBC patients with cirrhosis. HCC typically develops several years after the onset of cirrhosis, and is poorly predicted by prognostic models. In view of these findings, consideration should be given to careful screening for HCC in male PBC patients with cirrhosis. The risk of HCC development may be an additional reason to consider earlier transplantation in these patients.
Abstract 4485: Preclinical characterization of PWT33597, a dual inhibitor of PI3-kinase alpha and mTOR
Authors: David J. Matthews, Marie O'Farrell, Joyce James, Anna C. Giddens, Gordon W. Rewcastle, William A. Denny
Journal: Cancer Research (2011)

Abstract Phosphoinositide-3-kinase (PI3K) is an important mediator of tumor cell growth, survival and proliferation. In particular, PI3K alpha is important for signaling downstream of receptor tyrosine kinases and is also frequently amplified or mutationally activated in tumors, suggesting that selective inhibitors of this isoform may have therapeutic utility in the treatment of cancer. Downstream of PI3K, the mTOR kinase also plays a critical role in cellular growth and metabolism, and inhibitors of mTOR have demonstrated clinical benefit in several tumor types. We report here the discovery and characterization of PWT33597, a dual inhibitor of PI3K alpha and mTOR. PWT33597 inhibits PI3K alpha and mTOR in biochemical assays with IC50 values of 19 and 14 nM respectively, and is approximately 10-fold selective with respect to PI3K gamma and PI3K delta. Profiling of PWT33597 against 442 protein kinases (Ambit Kinomescan) revealed little or no cross-reactivity with either serine/threonine or tyrosine kinases, and there was little cross-reactivity with an additional panel of 64 pharmacologically relevant targets. In NCI-H460 and HCT116 tumor cells with mutationally activated PI3K alpha, PWT33597 inhibits phosphorylation of PI3K and mTOR pathway proteins with cellular IC50 values similar to its biochemical IC50 values. PWT33597 has good pharmacokinetic properties in multiple preclinical species, is not extensively metabolized in vivo and shows little potential for interaction with cytochrome P450 enzymes. Following a single oral dose in vivo, PWT33597 shows durable inhibition of PI3K and mTOR pathway signaling in xenograft tumors. High compound distribution into tumors and potent anti-tumor activity has been observed in multiple tumor xenograft models with activated PI3K/mTOR pathways. Also, administration of PWT33597 in mice is associated with transient increases in plasma insulin, consistent with an effect on PI3K/AKT signaling. A robust PK/PD relationship has been defined, which will guide interpretation of the planned phase I clinical study. IND-enabling studies with PWT33597 are currently in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4485. doi:10.1158/1538-7445.AM2011-4485
239 POSTOPERATIVE OUTCOME AFTER HEPATECTOMY CAN BE PREDICTED USING A NEW BEDSIDE TEST FOR MAXIMAL LIVER FUNCTION CAPACITY
Authors: M. Stockmann, J. Lock, B. Riecke, K. Heyne, P. Martus, M. Fricke, S. Lehmann, S. Niehues, M. Schwabe, A.J. Lemke, P. Neuhaus
Journal: Journal of Hepatology (2008)
DERMATITIS ARTEFACTA DUE TO CANTHARIDES PLASTER
Authors: F. Gardiner
Journal: BMJ (1930)

the stern lhollow.Oiie stud was inserted so that it mnade a corni- mnlulicationi betweeni the abdominial cavity and the space under- neath the aniteirior sheath of the lef't.. i ectus thle other, between tlhe abdominial cavity thlrouiglh the right r-ectus inito the sub- cnttanieous tissues.The studs were inserted at the level of thle lower cnd of the incision aiid about two inelhes to eitlher side of it, ini order to keeip thiern as far awav from omiienitimasi a possible.The wounid was tlheni sutured in layer1s.The after-results lhave beeni surpr isinigly good.Fr omi thle date of thle operation Mr. X lhas niot ceased to improve,.It, was tlhouiglht advisable to tap hlimn once more, teni day s after the opcerationi, owilng to a reaccumulation of fluid; 70 oz.were witlhdrawn, but since thlenthere has be'en nio more acctumulatien of fluid, anid cen examining him, oin October 1Otlh, T failed to detect any free fluid in tle al(lorninal cavitY.His weight lhad inicreased rapidlv, some- times 4 lb. in a wock, unitil oni the date menitioned it had reached 11 st.8 lb.He then felt exceedinigly well, anid lhad ain excellent
Emergence of High-Level Trimethoprim Resistance in Fecal<i>Escherichia coli</i>during Oral Administration of Trimethoprim or Trimethoprim-Sulfamethoxazole
Authors: Barbara E. Murray, Edward R. Rensimer, Herbert L. DuPont
Journal: New England Journal of Medicine (1982)

The effect of daily administration of trimethoprim (TMP), trimethoprim–sulfamethoxazole (TMP-SMX), or placebo on aerobically grown fecal gram-negative bacteria was monitored in 136 students from the United States during a two-week diarrhea-prevention study in Mexico. Unlike patients in other studies with these agents, who had urinary-tract infection or granulocytopenia, most persons in this study had no change in total fecal Enterobacteriaceae and had high-level TMP and SMX resistance in virtually all these strains. Escherichia coli was the predominant TMP-resistant organism isolated; 96 per cent of 165 TMP-resistant Esch. coli isolates were resistant to at least four antimicrobial agents, and 25 per cent were resistant to seven. TMP resistance was transferable in 40 of 100 strains tested. Despite the lack of TMP resistance in other studies of prophylaxis, our results clearly demonstrate the remarkable capacity for emergence and dissemination of resistance to this agent. (N Engl J Med. 1982; 306:130–5.)
Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the γ2 subunit of nicein/kalinin (LAMININ–5)
Authors: Daniel Aberdam, Marie-Florence Galliano, Joëlle Vailly, Leena Pulkkinen, Jeannette Bonifas, Angela M. Christiano, Karl Tryggvason, Jouni Uitto, Ervin H. Epstein, Jean-Paul Ortonne, Guerrino Meneguzzi
Journal: Nature Genetics (1994)
Eight telltale signs are linked to impending death in cancer patients
Authors: J. Wise
Journal: BMJ (2015)

Eight specific clinical signs associated with death within three days in patients with cancer have been identified in a study published online in the journal Cancer .

Knowing when death is imminent means that close family members can be informed, investigations and aggressive treatment can be discontinued, and the patient can be made comfortable, the authors noted.

Researchers studied 357 consecutive patients with advanced …
Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place
Authors: B Herreros, S M Rodríguez-Pinilla, R Pajares, M Á Martínez-Gónzalez, R Ramos, I Munoz, S Montes-Moreno, M Lozano, L Sánchez-Verde, G Roncador, M Sánchez-Beato, R D de Otazu, M Pérez-Guillermo, M J Mestre, C Bellas, M Á Piris
Journal: Leukemia (2010)
THE MEDICAL MANAGEMENT OF FRACTURES
Authors: CHARLES F. NELSON
Journal: JAMA (1941)

The subject of delayed union and nonunion of fractures is still in a state of confusion. The orthopedic surgeon has made great strides in his department of the practice of medicine, but this progress is limited largely to the mechanical aspects of orthopedics. He has not scientifically explained the causes of delayed union or nonunion of fractures or of bone disease, especially arthritis.  The literature on factors concerned in metabolism of bone is confusing and is to a great extent confined to the study of individual elements without due regard to the relationship of all the physicochemical processes involved and their clinical interpretation and application to growth and regeneration of bone.  Some suggestions as to the medical management of fractures, based on a large number of clinical cases as well as on considerable experimental evidence, should be of interest at this time. The suggestions offered here are based first on
Treatment recommendations for chronic hepatitis B: An evaluation of current guidelines based on a natural history study in the United States
Authors: Myron John Tong, Carlos Hsien, Leeyen Hsu, Hai‐En Sun, Lawrence Mitchell Blatt
Journal: Hepatology (2008)

Current guidelines for treatment of chronic hepatitis B include hepatitis B e antigen (HBeAg) status, levels of hepatitis B virus (HBV) DNA, and serum alanine aminotransferase (ALT) values in the setting of either chronic hepatitis or cirrhosis. Based on findings from a prospective study of hepatitis B surface antigen (HBsAg)-positive patients, we determined whether these guidelines included patients who developed hepatocellular carcinoma (HCC) and who died of non-HCC liver-related complications. The criteria for treatment from four published guidelines were matched to a cohort of 369 HBsAg-positive patients enrolled in the study. During a mean follow-up of 84 months, 30 patients developed HCC and 37 died of non-HCC liver-related deaths. Using criteria for antiviral therapy as stated by the four guidelines, only 20%-60% of the patients who developed HCC, and 27%-70% of patients who died of non-HCC liver-related deaths would have been identified for antiviral therapy according to current treatment recommendations. If baseline serum albumin levels of 3.5 mg/dL or less or platelet counts of 130,000 mm3 or less were added to criteria from the four treatment guidelines, then 89%-100% of patients who died of non-HCC liver-related complications, and 96%-100% of patients who developed HCC would have been identified for antiviral therapy. In addition, if basal core promoter T1762/A1764 mutants and precore A1896 mutants also were included, then 100% of patients who developed HCC would have been identified for treatment. Conclusion: This retrospective analysis showed that the current treatment guidelines for chronic hepatitis B excluded patients who developed serious liver-related complications. (HEPATOLOGY 2008.)
Skin bacteriology and the role of<i>Staphylococcus aureus</i>in infection
Authors: None Noble
Journal: British Journal of Dermatology (1998)

Many of the staphylococci and coryneforms that inhabit normal human skin do not cause skin disease. Amongst the remainder the mechanisms of pathogenicity vary widely. For Proteus, Pseudomonas and Brevibacterium species proteolysis is a major determinant. The precise role of Corynebacterium minutissimum in erythrasma and the propionibacteria in acne is not known. Staphylococcus aureus, however, produces a wide range of non-specific agents, such as haemolysins and leucocidins as well as highly specific toxins such as the epidermolytic toxins involved in bullous impetigo and scalded skin syndrome. Most of the current attention, however, is devoted to the role of the enterotoxins and toxic shock toxin as superantigens, with emphasis on their role in atopic dermatitis. Molecularly similar toxins in the streptococci play a similar role and may also have a role in the aetiology of psoriasis.
Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma
Authors: Christine F Skibola, Paige M Bracci, Eran Halperin, Lucia Conde, David W Craig, Luz Agana, Kelly Iyadurai, Nikolaus Becker, Angela Brooks-Wilson, John D Curry, John J Spinelli, Elizabeth A Holly, Jacques Riby, Luoping Zhang, Alexandra Nieters, Martyn T Smith, Kevin M Brown
Journal: Nature Genetics (2009)
FLT3 Mutation and Acute Myelogenous Leukemia with Leukostasis
Authors: Katherine A Thornton, Mark Levis
Journal: New England Journal of Medicine (2007)

A 59-year-old man presented with a sudden onset of abdominal pain in the left upper quadrant, associated with low-grade fever and shortness of breath. He had had a recent relapse of acute myelogenous leukemia and had an internal-tandem-duplication mutation of Fms-like tyrosine kinase 3 (FLT3). His white-cell count at admission was 15,900 per cubic millimeter, with 60% monoblasts. Over the next 24 hours, his leukocyte count increased from 29,000 to 102,340 per cubic millimeter, and his monoblast count increased from 5510 to 55,264 per cubic millimeter, despite the administration of cyclophosphamide. The patient's hypoxemia worsened. Mechanical ventilation was initiated, but . . .
Quinidine-lnduced Granulomatous Hepatitis
Authors: T. CHAJEK
Journal: Annals of Internal Medicine (1974)

Quinidine-induced liver disease has already been reported in three cases. The histologic picture, however, has not been described so far. We report a patient in whom liver damage developed after quinidine administration and for whom, on liver biopsy, granulomatous hepatitis was diagnosed.
Physicochemical and Biological Properties of Human and Canine Plasmins
Authors: Y. Takeda, M. Nakabayashi
Journal: Journal of Clinical Investigation (1974)

Three kinds of plasmin were found to be generated when plasminogen or [125I]plasminogen was incubated at 32°C for longer than 20 min in urokinase and 50% glycerol. Each plasmin was then separated by G-200 or G-75 Sephadex filtration, and its physicochemical properties were determined. The molecular weights of the three plasmins as determined by G-200 Sephadex filtration were 125,000±5,000(SD), 63,000±2,000(SD), and 31,500±1,000(SD), and those by sodium dodecyl sulfate(SDS)-polyacrylamide electrophoresis were 130,000±5,000(SD), 64,000±3,000(SD), and 32,000±1,500(SD). It was also found that during the incubation of the smallest plasmin in SDS and beta-mercaptoethanol it was further split into two smaller pieces of about 16,000 mol wt and that polymer proteins of 95,000±2,000(SD) and 48,000±1,500(SD) mol wt were formed. Despite these differences in the molecular size of the three plasmins, the specific activity of each plasmin was closely similar and in case of human plasmins averaged 29±0.9(SD) CTA units/mg plasmin and in case of canine plasmins 8.5±0.54(SD) CTA units/mg plasmin. Then, using human plasmin of the smallest size (mol wt 31,500), the total plasma antiplasmin capacity was determined in 20 normal human plasma, which averaged 7.8±2(SD) CTA units of plasmin per milliliter plasma. Studies were next made of the affinity of human [125I]-plasmin of the smallest size with albumin, gamma globulin, α2-macroglobulin, α1-antitrypsin, fibrinogen, and fibrin. The results were 0%, 0%, 14.6±0.5(SD)%, 17.6±0.6(SD)%, 21±0.5(SD)%, and 20.5±0.6(SD)%, respectively, of [125I]plasmin available and were unaltered when the amount of [125I]plasmin was increased to twice and four times the original amount. Finally, the plasma disappearance half-life of canine [125I]plasmin of the smallest size was studied in five healthy dogs, which averaged 14.2±0.63(SD) h. These results support the concept that the combination between plasmin and plasmin inhibitors is reversible and indicate that fibrinogen and fibrin have greater affinities than α2-macroglobulin or α1-antitrypsin.
Medical Mystery — An Unusual Complication of Colonoscopy
Authors: Marc A Gladman, Shukri S Shami
Journal: New England Journal of Medicine (2007)

This 69-year-old man presented with left-sided lower abdominal and groin pain that began 36 hours after a colonoscopy. He had diverticular disease and had undergone polypectomy of a dysplastic adenoma of the sigmoid colon. He was hypotensive and febrile with a palpable, tender mass in the groin.
Hemodialysis for Methyprylon (Noludar®) Poisoning
Authors: MELVIN YUDIS
Journal: Annals of Internal Medicine (1968)

A case of methyprylon (Noludar®) poisoning treated with extracorporeal hemodialysis is reported. The patient showed dramatic clinical improvement with concomitant lowering of serum methyprylon levels from 4 to 0.4 mg/100 ml during a 9-hr period of dialysis. Only negligible quantities of methyprylon were recovered from the bath. In vitro dialysis of methyprylon revealed this drug to be readily dialyzable with a coil clearance of 42 ml/min, about equal to that of the short-acting barbiturates. Less than 10% of the ingested dose of methyprylon was recovered in the cumulative dialysates of both our patient and the one other case in the literature. It is therefore concluded that endogenous metabolism accounts for the rapid decrease in serum levels of methyprylon. Dialysis of toxic metabolites of the drug may possibly explain the dramatic clinical improvement seen with the reported cases of hemodialysis after methyprylon intoxication. The value of hemodialysis in methyprylon intoxication remains to be proved in view of the small total amount recoverable in the dialysates.
Joint Commission Begins Tracking Outcome Data
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

EARLIER THIS year, the Joint Commission on Accreditation of Healthcare Organizations launched an initiative to incorporate patient outcomes into its accreditation process for hospitals and other health care organizations. The initiative, called ORYX, will allow the Joint Commission to review data trends and patterns and to use the data to help health care organizations improve patient care, said Dennis S. O'Leary, MD, president of the Oakbrook Terrace, Ill—based group. The Joint Commission is the nation's predominant standard-setting and accrediting body in health care. The independent, not-for-profit commission evaluates and accredits nearly 18000 health care organizations and programs in the United States. "The Joint Commission's primary mission is to improve the quality of care provided to the public through the provision of health care accreditation and related services that support performance improvement in health care organizations," O'Leary said. "We are now in transition from being a standards-based, risk-reduction organization that, in
Oral Fluoroquinolone Therapy for Clostridium difficile Enterocolitis-Reply
Authors: Ludwig A. Lettau
Journal: JAMA (1989)

In Reply.—  My report of two patients with C difficile toxin—positive diarrhea that resolved after simply changing from parenteral ceftriaxone therapy to oral ciprofloxacin therapy was not meant to advocate the use of fluoroquinolones for treatment of C difficile —associated enterocolitis but rather was intended to stimulate controlled investigation of an apparent lack of their association.  I cannot reconcile my anecdotal experience with the case report of Dr Loge, but one could speculate that there might be variable sensitivity of C difficile strains to ciprofloxacin or perhaps that the antibiotic dose (750 vs 500 mg) or fecal antibiotic concentration played a role. Host factors such as age, concurrent gut flora, intrinsic intestinal disease, and other underlying illness also could contribute to induction or resolution of C difficile —associated disease.  It seems that the pathogenesis of C difficile enterocolitis in individual cases remains poorly understood. There are reports of spontaneous occurrence
Physical Education and the Study of Sport
Authors: Nancy Laurenson
Journal: British Journal of Sports Medicine (1991)

Section III deals with treatment approaches to restore normal move- ment of the foot and ankle using orthotics, physiotherapy or surgery.The chapter covering the fabrication of orthotic devices, which is supple- mented by some interesting case studies, is bound to be of interest to various disciplines involved with the treatment of foot and ankle problems.This book forms part of a series of monographs covering Contemporary Perspectives in Rehabilitation.The objective of this series is to provide compre- hensive and clinically relevant presen- tations which are challenging for both the student and clinician.This volume clearly achieves this objective.