tbuckley/cabot-search huggingface dataset:
Referral management centres: General practitioner colleagues could refer among themselves
Authors: Graeme Mackenzie
Journal: BMJ (2006)

EDITOR—I have no real objections to my referrals being triaged by clinicians.1 Iam under no illusions that referral is used as an “option” for general practitioners, and that we use it sometimes inappropriately just to be seen to be doing something. Of course medicolegally it is a powerful defence, …
Recent Antihyperglycemic Prescribing Trends for U.S. Privately Insured Patients With Type 2 Diabetes
Authors: Fredric J. Cohen, Cheryl A. Neslusan, Jonathan E. Conklin, Xue Song
Journal: Diabetes Care (2003)

OBJECTIVE—The mid-1990s witnessed the introduction of new classes of medications to treat hyperglycemia of type 2 diabetes. There is evidence that these newer classes have found a place in the therapeutic armamentarium, but details of their use patterns are not known. We sought to determine whether antihyperglycemic prescribing patterns changed concurrently with new drug introductions, and whether such changes were related to changes in the underlying patient population. RESEARCH DESIGN AND METHODS—A sample of U.S. privately insured patients with suspected type 2 diabetes was identified from the MarketScan Research Database over the period of 1997–2000. Patients with type 2 diabetes were identified among those continuously enrolled in the database for at least 1 year. Drug therapy episodes were defined by sequential fulfillment of prescriptions implying a continuous supply of a particular drug (or combination) of at least 30 days duration. Univariate analyses were used to explore trends over time in drug prescriptions and patient characteristics. Multivariate logistic regressions were used to isolate the impact of year from other variables on the likelihood of receiving prescriptions for a specific therapy. RESULTS—A total of 232,020 unique diabetic patients had an average of 1.91 diabetes drug therapy episodes between 1997 and 2000. Monotherapy with sulfonylureas decreased, but monotherapy with thiazolidinedione, metformin, and other oral antihyperglycemics increased over time. Combinations of sulfonylureas and metformin; sulfonylureas and thiazolidinedione; metformin and thiazolidinedione; and sulfonylureas, metformin, and thiazolidinedione each increased over the time interval. Insulin monotherapy decreased, as did insulin combination therapy with sulfonylureas. The combination of insulin and metformin increased, whereas insulin and thiazolidinedione was stable. The influence of year on prescribing patterns remained highly significant (P &amp;lt; 0.001) after adjusting for patient characteristics. CONCLUSIONS—Antihyperglycemic prescription patterns in the U.S. have changed in recent years in parallel with, and probably as a direct result of, the introduction of different classes of medications to the marketplace. Overall, the prescribing trend has been away from monotherapy with insulins and sulfonylureas and toward combination therapies, presumably in attempts to reduce hypoglycemic symptoms and to achieve better glucose control.
Prostate Cancer Mortality in the Finnish Randomized Screening Trial
Authors: T. P. Kilpelainen, T. L. Tammela, N. Malila, M. Hakama, H. Santti, L. Maattanen, U.-H. Stenman, P. Kujala, A. Auvinen
Journal: JNCI Journal of the National Cancer Institute (2013)

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.
Officials warn of multiple drug resistance in the community
Authors: R. Dobson
Journal: BMJ (2003)

Bacteria with multiple resistance to antibiotics, until now found only in UK hospitals, may have emerged in the community.

Samples taken from 57 patients, mostly with urinary tract infections, in two parts of the United Kingdom, have shown evidence of Escherichia coli with multiple resistance to drugs.

The findings, reported by the Health Protection Agency, may indicate that resistant bacteria are emerging in the community independently of hospital settings, with significant implications for the way GPs treat urinary tract infections, one of the more common conditions they see.

The agency says that enterobacteriaceae …
Unscheduled DNA Synthesis in Human Bronchial Epithelium Treated With Various Chemical Carcinogens In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Ishikawa, Takatoshi, Ide, Fumio, Kodama, Ken-ichi, Takayama, Shozo
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Unscheduled DNA Synthesis in Human Bronchial Epithelium Treated With Various Chemical Carcinogens In Vitro Get access Takatoshi Ishikawa, Takatoshi Ishikawa 5Department of Experimental Pathology, Cancer Institute (Japanese Foundation for Cancer Research), Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Fumio Ide, Fumio Ide 5Department of Experimental Pathology, Cancer Institute (Japanese Foundation for Cancer Research), Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ken-ichi Kodama, Ken-ichi Kodama 5Department of Experimental Pathology, Cancer Institute (Japanese Foundation for Cancer Research), Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shozo Takayama Shozo Takayama 5Department of Experimental Pathology, Cancer Institute (Japanese Foundation for Cancer Research), Kami-Ikebukuro, Toshima-ku, Tokyo 170, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 1, July 1984, Pages 101–106, https://doi.org/10.1093/jnci/73.1.101 Published: 01 July 1984 Article history Received: 09 December 1983 Accepted: 15 February 1984 Published: 01 July 1984
Proteolytic processing is required for viral superantigen activity.
Authors: C G Park, M Y Jung, Y Choi, G M Winslow
Journal: The Journal of Experimental Medicine (1995)

The mouse mammary tumor virus-7 superantigen (vSAG7) is proteolytically processed in B cells at as many as three positions. Proteolytic processing appears to be important for superantigen activity because a processed form of vSAG7 was predominant among those forms that were found to bind to major histocompatibility complex class II molecules. To determine the functional significance of proteolytic processing, a mutation was introduced in vSAG7 at one of the sites where proteolytic cleavage is thought to take place in B cells. Elimination of the putative processing site at position 171 abrogated detectable vSAG7 surface expression in B cells, indicating that proteolytic processing is required for vSAG7 function. Coexpression in insect cells of vSAG7 and furin, a proprotein-processing enzyme, also demonstrated that furin could process vSAG7 at position 171.
DEVELOPMENT OF CHICKEN LYMPHOID SYSTEM
Authors: Yong Sung Choi, Robert A. Good
Journal: The Journal of Experimental Medicine (1972)

Synthesis and secretion of Ig by chicken lymphoid cells was studied. Both spleen and bursa cells synthesize and secrete IgM and IgG whereas Ig was not detected in thymus cells. In contrast to the spleen cells which synthesize H and L chains in balanced quantities, the bursa cells synthesize and secrete free L chains. In addition to the lymphoid cells which secrete IgM or IgG, the bursa appears to contain a cell population which synthesizes nonsecretory Ig. The structure of this Ig was studied by specific serological precipitation and by SDS-acrylamide gel electrophoresis. The H chains of this nonsecretory Ig are serologically related to µ-chains and exhibit a smaller molecular weight (i.e., ∼50,000) in SDS-acrylamide gel electrophoresis than H chains of IgG and IgM synthesized by the spleen cells (i.e., ∼70,000).
Hereditary Distal Renal Tubular Acidosis: New Understandings
Authors: Daniel Batlle, Hrishikesh Ghanekar, Sheeja Jain, Amit Mitra
Journal: Annual Review of Medicine (2001)

▪ Abstract The primary or hereditary form of distal renal tubular acidosis (dRTA), although rare, has received increased attention recently because of dramatic advances in the understanding of its genetic basis. The final regulation of renal acid excretion is effected by various acid/base transporters localized in specialized cells in the cortical collecting and outer medullary collecting tubules. Inherited defects in two of the key acid/base transporters involved in distal acidification, as well as mutations in the cytosolic carbonic anhydrase gene, can cause dRTA. The syndrome is inherited in both autosomal dominant and recessive patterns; patients with recessive dRTA present with either acute illness or growth failure at a young age, sometimes accompanied by deafness, whereas dominant dRTA is usually a milder disease and involves no hearing loss. The AE1 gene encodes two Cl − /HCO 3 − exchangers that are expressed in the erythrocyte and in the acid-secreting intercalated cells of the kidney. AE1 contributes to urinary acidification by providing the major exit route for HCO 3 − across the basolateral membrane. Several mutations in the AE1 gene cosegregate with dominant dRTA. The modest degree of hypofunction exhibited in vitro by these mutations, however, does not explain the abnormal distal acidification phenotype. Other AE1 mutations have been linked to a recessive syndrome of dRTA and hemolytic anemia in which hypofunction can be discerned by in vitro studies. Several mutations in the carbonic anyhdrase II gene are associated with the autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. Some of these individuals present with deafness of the conductive type. By contrast, more recent studies have shown that mutations in ATP6B1, encoding the B-subtype unit of the apical H + ATPase, are responsible for a group of patients with autosomal recessive dRTA associated with sensorineural deafness. Thus, the presence of deafness and the type provide an important clue to the genetic lesion underlying hereditary dRTA.
Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo-Controlled, Double-Blind Trial From the ORN96 Study Group
Authors: Djillali Annane, Joël Depondt, Philippe Aubert, Maryvonne Villart, Pierre Géhanno, Philippe Gajdos, Sylvie Chevret
Journal: Journal of Clinical Oncology (2004)

To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis.This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety.At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms.Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.
Risk Factors and Comorbidities in the Preclinical Stages of Chronic Obstructive Pulmonary Disease
Authors: Hans Van Remoortel, Miek Hornikx, Daniel Langer, Chris Burtin, Stephanie Everaerts, Peter Verhamme, Steven Boonen, Rik Gosselink, Marc Decramer, Thierry Troosters, Wim Janssens
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD).Objectives: This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening.Methods: Sixty subjects with preclinical COPD (63 ± 6 yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 ± 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 ± 6 yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively.Measurements and Main Results: The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities.Conclusions: Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction.Clinical trial registered with www.clinicaltrials.gov (NCT 01314807).
Zoledronate for prevention of bone erosion in tophaceous gout: a randomised, double-blind, placebo-controlled trial
Authors: Nicola Dalbeth, Opetaia Aati, Gregory D Gamble, Anne Horne, Meaghan E House, Mark Roger, Anthony J Doyle, Ashika Chhana, Fiona M McQueen, Ian R Reid
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout. <h3>Methods</h3> This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies. <h3>Results</h3> There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p<sub>(treat)</sub>=0.10, p<sub>(time)</sub>=0.47, p<sub>(treat*time)</sub>=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and β-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains. <h3>Conclusions</h3> Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.
A Conduit System Distributes Chemokines and Small Blood-borne Molecules through the Splenic White Pulp
Authors: Martijn A. Nolte, Jeroen A.M. Beliën, Inge Schadee-Eestermans, Wendy Jansen, Wendy W.J. Unger, Nico van Rooijen, Georg Kraal, Reina E. Mebius
Journal: The Journal of Experimental Medicine (2003)

Access to the splenic white pulp is restricted to lymphocytes and dendritic cells. Here we show that movement of molecules from the blood into these confined areas is also limited. Large molecules, such as bovine serum albumin (68 kD), immunoglobulin G (150 kD), and 500 kD dextran are unable to enter the white pulp, whereas smaller blood-borne molecules can directly permeate this compartment. The distribution is restricted to a stromal network that we refer to as the splenic conduit system. The small lumen of the conduit contains collagen fibers and is surrounded in the T cell areas by reticular fibroblasts that express ER-TR7. It also contains the chemokine CCL21. Conversely, in B cell follicles the B cell-attracting chemokine CXCL13 was found to be associated with the conduit and absence of ER-TR7+ fibroblasts. These results show heterogeneity of reticular fibroblasts that enfold the conduit system and suggest that locally produced chemokines are transported through and presented on this reticular network. Therefore, the conduit plays a role in distribution of both blood-borne and locally produced molecules and provides a framework for directing lymphocyte migration and organization of the splenic white pulp.
HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients
Authors: P Storti, G Donofrio, S Colla, I Airoldi, M Bolzoni, L Agnelli, M Abeltino, K Todoerti, M Lazzaretti, C Mancini, D Ribatti, S Bonomini, V Franceschi, V Pistoia, G Lisignoli, A Pedrazzini, O Cavicchi, A Neri, V Rizzoli, N Giuliani
Journal: Leukemia (2010)
Cholera Surveillance during the Haiti Epidemic — The First 2 Years
Authors: Ezra J. Barzilay, Nicolas Schaad, Roc Magloire, Kam S. Mung, Jacques Boncy, Georges A. Dahourou, Eric D. Mintz, Maria W. Steenland, John F. Vertefeuille, Jordan W. Tappero
Journal: New England Journal of Medicine (2013)

In October 2010, nearly 10 months after a devastating earthquake, Haiti was stricken by epidemic cholera. Within days after detection, the Ministry of Public Health and Population established a National Cholera Surveillance System (NCSS).The NCSS used a modified World Health Organization case definition for cholera that included acute watery diarrhea, with or without vomiting, in persons of all ages residing in an area in which at least one case of Vibrio cholerae O1 infection had been confirmed by culture.Within 29 days after the first report, cases of V. cholerae O1 (serotype Ogawa, biotype El Tor) were confirmed in all 10 administrative departments (similar to states or provinces) in Haiti. Through October 20, 2012, the public health ministry reported 604,634 cases of infection, 329,697 hospitalizations, and 7436 deaths from cholera and isolated V. cholerae O1 from 1675 of 2703 stool specimens tested (62.0%). The cumulative attack rate was 5.1% at the end of the first year and 6.1% at the end of the second year. The cumulative case fatality rate consistently trended downward, reaching 1.2% at the close of year 2, with departmental cumulative rates ranging from 0.6% to 4.6% (median, 1.4%). Within 3 months after the start of the epidemic, the rolling 14-day case fatality rate was 1.0% and remained at or below this level with few, brief exceptions. Overall, the cholera epidemic in Haiti accounted for 57% of all cholera cases and 53% of all cholera deaths reported to the World Health Organization in 2010 and 58% of all cholera cases and 37% of all cholera deaths in 2011.A review of NCSS data shows that during the first 2 years of the cholera epidemic in Haiti, the cumulative attack rate was 6.1%, with cases reported in all 10 departments. Within 3 months after the first case was reported, there was a downward trend in mortality, with a 14-day case fatality rate of 1.0% or less in most areas.
Psychotherapy with the Children or Disciples of Charismatic Individuals
Authors: MILTON H. MILLER, LEIGH M. ROBERTS
Journal: American Journal of Psychiatry (1967)

The child of an individual whom society has identified as charismatic may find it difficult to achieve the individuality and freedom for independent growth necessary to his own maximal adjustment and self-realization. In working with such a patient, the therapist should attempt neither to destroy the image of the "great man" nor to offer himself to the patient as a substitute. He may be able to foster a corrective emotional experience by focusing upon aspects of the patient's presentation from which his family is excluded.
TREATMENT OF URTICARIA WITH COLLOSOL MANGANESE
Authors: H. M. Mitchell
Journal: BMJ (1923)

depends on the relative production of a haemolysin or a neurotoxin.We would suggest a similar genesis in many instances of rheumatoid arthritis by means of a toxin with a special affinity for synovial membrane.However, it must always be remembered that the whole metabolism is upset, and further work is required to inves- tigate other possible factors responsible for the production of the clinical changes observed.Many observers have assigned importance to the isolation of various strains of streptococci from the stools, but the results are so far very variable and no reliable conclusions can be drawn.It is possible that the factor of achlorhydria may have some influence in determining this state of affairs, in view of the work of Billings7 and his collaborators on the variability of streptococcal strains in different media.We wish to thank Dr. Munro,