tbuckley/cabot-search huggingface dataset:
Clinic Training of the Family Physician
Authors: Daniel J. Woiwode
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The survey by Brown et al<sup>1</sup>of the clinical content of general practice in Massachusetts revealed that 78% of patients were cared for outside the hospital and 25% of patient visits were for health maintenance problems. It was apparently on findings such as these that the authors concluded that a different type of training would be needed for future family physicians. We are afraid your readers will be misled by this conclusion; the proposed "different" training is<i>precisely</i>the orientation of many current family practice residencies. The AMA Ad Hoc Committee of Education for Family Practice recommended: Emphasis (should be placed) upon the ambulatory patient, upon diseases of high incidence, chronic diseases, emotional and behavioral problems, preventive medicine, health maintenance, and rehabilitation.<sup>2</sup> The modern family practice residencies carry out the above recommendations through the use of a model clinic as a training facility.<sup>3</sup>Preliminary
Providing services for drug misusers: what lessons from North America?
Authors: P M Fleming
Journal: BMJ (1988)

New York has the largest number of intravenous drug users in the United States. As there is a high prevalence of infection from human immunodeficiency virus (HIV) among this group the city has had to confront issues that will face others in the future.12 Health professionals have had to look at ways of reducing high risk behaviour among intravenous drug users, such as using and sharing dirty syringes and needles, and there is some evidence that addicts are changing their behaviour.34 These changes are insufficient, however, and those most at risk?young intravenous drug users? seem most resistant to change. Only a proportion of drug users are in contact with the treatment services and great efforts have been made to try and reach the rest.5 This is a group to which we in the United Kingdom will need to pay attention. The National Institute on Drug Abuse (part of the United States Department of Health and Human Services) is funding two AIDS demonstration projects.6 In one, multiple outreach or early intervention methods will be used to try to communicate information on AIDS to high risk individuals in five cities. In the other different outreach models will be evaluated to find which work best in reaching different target populations. In New York drug users, ex users, and health professionals have set up the Association for Drug Abuse, Prevention, and Treatment to educate addicts about AIDS, give support to the sick, and try to reduce the spread of HIV by drug users.7 As a result of such efforts more drug users are coming forward for treatment than the services can cope with.5 The methadone programme in New York is oversubscribed and there are waiting lists for treatment. The concern is that if treatment is not available addicts will disappear and the efforts to reduce HIV infection will be undermined. Similar pressures could occur in the United Kingdom. The rehabilitation services in the United States are having to cope with dying patients as AIDS presents in residents in drug rehabilita? tion units and among ex-addict staff members. We will also have to train and support staff to deal with these problems.
IMPAIRMENT OF URIC ACID EXCRETION IN GOUT*
Authors: Willoughby Lathem, Gerald P. Rodnan
Journal: Journal of Clinical Investigation (1962)

The urinary excretion and renal clearance of uric acid were determined in 10 nongouty control subjects and in 11 patients with primary gout.The nongouty subjects, all but two of whom (M.W. and D.B.) were males,
Integrating mechanisms of pulmonary fibrosis
Authors: Thomas A. Wynn
Journal: The Journal of Experimental Medicine (2011)

Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with limited therapeutic options. Although research on the pathogenesis of pulmonary fibrosis has frequently focused on the mechanisms that regulate the proliferation, activation, and differentiation of collagen-secreting myofibroblasts, recent studies have identified new pathogenic mechanisms that are critically involved in the initiation and progression of fibrosis in a variety of settings. A more detailed and integrated understanding of the cellular and molecular mechanisms of pulmonary fibrosis could help pave the way for effective therapeutics for this devastating and complex disease.
MTHFR 677C→T Polymorphism and Risk of Coronary Heart Disease
Authors: Mariska Klerk, Petra Verhoef, Robert Clarke, Henk J. Blom, Frans J. Kok, Evert G. Schouten, None and the MTHFR Studies Collaboration Group
Journal: JAMA (2002)

ContextIn observational studies, individuals with elevated levels of plasma homocysteine tend to have moderately increased risk of coronary heart disease (CHD). The MTHFR 677C→T polymorphism is a genetic alteration in an enzyme involved in folate metabolism that causes elevated homocysteine concentrations, but its relevance to risk of CHD is uncertain.ObjectiveTo assess the relation of MTHFR 677C→T polymorphism and risk of CHD by conducting a meta-analysis of individual participant data from all case-control observational studies with data on this polymorphism and risk of CHD.Data SourcesStudies were identified by searches of the electronic literature (MEDLINE and Current Contents) for relevant reports published before June 2001 (using the search terms MTHFR and coronary heart disease), hand searches of reference lists of original studies and review articles (including meta-analyses) on this topic, and contact with investigators in the field.Study SelectionStudies were included if they had data on the MTHFR 677C→T genotype and a case-control design (retrospective or nested case-control) and involved CHD as an end point. Data were obtained from 40 (34 published and 6 unpublished) observational studies involving a total of 11 162 cases and 12 758 controls.Data ExtractionData were collected on MTHFR 677C→T genotype, case-control status, and plasma levels of homocysteine, folate, and other cardiovascular risk factors. Data were checked for consistency with the published article or with information provided by the investigators and converted into a standard format for incorporation into a central database. Combined odds ratios (ORs) for the association between the MTHFR 677C→T polymorphism and CHD were assessed by logistic regression.Data SynthesisIndividuals with the MTHFR 677 TT genotype had a 16% (OR, 1.16; 95% confidence interval [CI], 1.05-1.28) higher odds of CHD compared with individuals with the CC genotype. There was significant heterogeneity between the results obtained in European populations (OR, 1.14; 95% CI, 1.01-1.28) compared with North American populations (OR, 0.87; 95% CI, 0.73-1.05), which might largely be explained by interaction between the MTHFR 677C→T polymorphism and folate status.ConclusionsIndividuals with the MTHFR 677 TT genotype had a significantly higher risk of CHD, particularly in the setting of low folate status. These results support the hypothesis that impaired folate metabolism, resulting in high homocysteine levels, is causally related to increased risk of CHD.
309 ALTERING CO-INHIBITORY AND CO-STIMULATORY PATHWAYS TO RESTORE ANTI-VIRAL T CELL RESPONSES IN CHRONIC HBV INFECTION
Authors: A. Schurich, P. Khanna, M. Lubowiecki, A.R. Lopes, D. Peppa, L. Micco, G. Nebbia, H. Singh, W. Rosenberg, P.T.F. Kennedy, G. Dusheiko, M. Maini
Journal: Journal of Hepatology (2011)
The inverse care law
Authors: T. Dalrymple
Journal: BMJ (2012)

In 1971 Julian Tudor Hart, a general practitioner in South Wales, proposed his inverse care law: “The availability of good medical care tends to vary inversely with the need for the population served.” One might extend this a little: “The concern of a population for its own health tends to vary inversely with the actual state of health of that population.”

There is a good literary illustration of this in W W Jacobs’s short story “A Circular Tour.” Jacobs (1863-1943) was immensely popular in his day for his humorous stories of sailors ashore, his most famous book being Many Cargoes , published in 1896. He also wrote stories of the supernatural, the best known being “The Monkey’s Paw,” in which …
Defects in antigen-specific immune tolerance in continuous B cell lines from autoimmune mice.
Authors: M S Brooks, M Aldo-Benson
Journal: Journal of Clinical Investigation (1986)

B cell hyperactivity and resistance to tolerance induction are well-recognized immunologic abnormalities associated with both human and murine models of systemic lupus erythematosus. Studies evaluating the role of B cells in these defects have been complicated by the difficulties of consistently isolating large numbers of B cells from T cells and other host-derived regulatory factors. We have recently developed continuous cell lines of B lymphocytes with a high degree of specificity for the antigen dinitrophenyl (DNP) from both New Zealand black times New Zealand white F1 hybrid (BWF1) and BALB/c mice, and we used them to study intrinsic B cell defects in autoimmunity. We found that the kinetics of the immune response to the antigen DNP-Ficoll of both the BWF1 and BALB/c B cell lines are not different. In addition, the BWF1 cell lines, like the BALB/c cell lines and normal B cells, require nonspecific T cell-derived factors as well as antigen to produce an immune response. Tolerance was tested in the BWF1 B cells by preincubating them with DNP-murine IgG2a (MGG), which can induce tolerance in BALB/c cell line lymphocytes. The BWF1 B cell lines were resistant to tolerance induction by DNP-MGG and required 50-fold higher dose of DNP-MGG than BALB/c cell lines for suppression. They were also relatively resistant to tolerance with trinitrophenyl-d-glutamyl lysine. Thus, DNP-specific B cells from autoimmune mice have an inherent defect in tolerance induction.
Website of the week: Drinking, driving, and playing Tetris
Authors: M. Mullner
Journal: BMJ (2002)

The factsheet of the Campaign Against Drinking and Driving (CADD) (www.cadd.org.uk/facts.htm) speaks a clear language: drinking and driving is a bad thing. And, as CADD correctly points out, you can't calculate from what you drink whether you will exceed the legal limits. Blood alcohol levels are determined by several biological variables such as sex, body weight, and speed …
Recording and Visual Oscillometry by a New Standardized Technic
Authors: JULIUS A. OSHLAG, A. WILBUR DURYEE
Journal: Circulation (1950)

Oscillometry offers knowledge of clinical importance, yet its value in presently used apparatus has recently been questioned. The criticisms include shifting base line, parallax in visual reading, aging of rubber parts with consequent loss of elasticity, friction and inertia of writing mechanisms, and failure to standardize. The method suggested below obviates these defects.
IMPACT OF THE 2005 RESUSCITATION GUIDELINES ON PATIENT SURVIVAL: EXPERIENCE FROM A PROSPECTIVE REGISTRY IN A MIDDLE-EASTERN COUNTRY (2002-2010)
Authors: Amar Salam, Hajar Albinali, Rajvir Singh, Nidal Asaad, Awad Alqahtani, Abdurrazzak Gehani, Jassim Al Suwaidi
Journal: Journal of the American College of Cardiology (2013)
The Occurrence of Single-Stranded DNA in the Serum of Patients with Systemic Lupus Erythematosus and Other Diseases
Authors: David Koffler, Vincent Agnello, Robert Winchester, Henry G. Kunkel
Journal: Journal of Clinical Investigation (1973)

Single-stranded DNA (SDNA) occurs in high incidence and in greatest concentration in the sera of patients with systemic lupus erythematosus (SLE), where levels as high as 250 mug/ml were observed. SDNA appears to be an imunogen for anti-SDNA antibodies and forms complexes in vivo of both anti-SDNA-SDNA and anti-NDNA-SDNA types, which apparently play a role in the pathogenesis of the glomerulonephritis found in patients with SLE, SDNA is also found in high incidence but at lower levels in the sera of patients with rheumatoid arthritis. Lesser amounts of SDNA are found in several other diseases in which a low incidence of anti-SDNA antibodies is observed.
Regulation of rabbit myometrial alpha adrenergic receptors by estrogen and progesterone.
Authors: L T Williams, R J Lefkowitz
Journal: Journal of Clinical Investigation (1977)

The effects of estrogen and progesterone on uterine alpha-adrenergic receptors were investigated by direct receptor-binding studies. Immature female rabbits were primed with estrogen by intramuscular injections for 4 days. Other rabbits were primed with progesterone by injections of estrogen for 4 days followed by injections of progesterone for 4 days. The alpha adrenergic antagonist, [3H]dihydroergocryptine, was used to directly assess the number and affinity of alpha adrenergic receptors in membranes derived from estrogen-and progesterone-primed uteri. Membranes from estrogen-primed uteri contained 257 +/- 52 fmol of [3H]dihydroergocryptine-binding sites per mg protein whereas membranes from progesterone-primed uteri contained 83 +/- 11 fmol of of binding sites per mg protein. This reduction of alpha adrenergic receptor-binding sites by progesterone was statistically significant (P less than 0.02). In contrast, no significant difference in the binding site affinity was observed between the estrogen- and progesterone-primed groups. The progesterone-induced decrease in the number of uterine alpha adrenergic receptors provides a potential explanation for the reduced alpha adrenergic contractile response to epinephrine in the progesterone-primed myometrium.
Developers of the Hepatitis B Vaccine
Authors: Alain Braillon
Journal: JAMA (2009)

air at VA facilities, one of the many pieces of unfinished business beyond those major issues that we discussed in our Commentary. We agree that all facilities where current and past military personnel serve and receive treatment should be 100% smoke-free and note the recent Institute of Medicine report Combating Tobacco in Military and Veteran Populations. The report, which was commissioned by the Department of Defense (DOD) in 2007, calls for the DOD to set a timeline to eliminate smoking on military installations. The report also recommends that the DOD stop selling tobacco products in military commissaries and exchanges, prohibit tobacco use anywhere on military installations, and treat tobacco use in the same way as other health-related behaviors, such as alcohol abuse and poor physical fitness. We join Matthews and the Institute of Medicine in urging the VA and the DOD to take more immediate steps to protect the health of the men and women who serve in the armed services, as well as the civilians (such as Dr Matthews) working to serve them.
Abstract 1405: Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu over-expressing transgenic mouse model.
Authors: Connie S. Zhang, Peter A. Greer
Journal: Cancer Research (2013)

Abstract Fes (a.k.a. Fps) is a cytoplasmic protein tyrosine kinase that is highly expressed in breast epithelial cells during lactation, as well as in vascular endothelial and myeloid cells. Retrovially encoded oncogenic alleles of Fes are associated with tumors in chickens and cats and cause tumors in transgenic mice; however, a role for Fes in human cancer has not been established. Using an orthotopic mouse mammary engraftment model, we previously found that Fes deficiency correlated with reduction in engrafted tumor growth rates, lung metastasis, and circulating tumor cells. Reduced vascularity and fewer infiltrating macrophages suggested the tumor microenvironment of Fes-deficient mice was less supportive of tumor growth and metastasis. In co-culture with tumor cells, Fes-deficiency in macrophages correlated with a reduced ability to promote tumor cell invasive behavior. These results suggested a tumor promoting role of Fes kinase in breast cancer through roles in cells of the tumor microenvironment. In a transgenic mouse model of breast cancer driven by an activated HER2/Neu allele expressed in the mammary epithelium, we observed delayed tumor onset in Fes-deficient mice compared to wild-type mice. However, there was no difference in tumor growth rates. Taken together, these observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages, or by delaying breast tumor onset in women with HER2 overexpression. Citation Format: Connie S. Zhang, Peter A. Greer. Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu over-expressing transgenic mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1405. doi:10.1158/1538-7445.AM2013-1405 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Aspirin and Ticlopidine for Prevention of Recurrent Stroke in Black Patients&lt;SUBTITLE&gt;A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Philip B. Gorelick
Journal: JAMA (2003)

ContextBlacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.ObjectiveTo determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.Design, Setting, and PatientsRandomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.InterventionA total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.Main Outcome MeasuresRecurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.ResultsThe blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P = .12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P = .08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P = .12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P = .69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.ConclusionsDuring a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.
Maternal Exposure to Ambient Levels of Benzene and Neural Tube Defects among Offspring: Texas, 1999–2004
Authors: Philip J. Lupo, Elaine Symanski, D. Kim Waller, Wenyaw Chan, Peter H. Langlois, Mark A. Canfield, Laura E. Mitchell
Journal: Environmental Health Perspectives (2010)

Previous studies have reported positive associations between maternal exposure to air pollutants and several adverse birth outcomes. However, there have been no studies assessing the association between environmental levels of hazardous air pollutants, such as benzene, and neural tube defects (NTDs), a common and serious group of congenital malformations.
Are Popular Attitudes Toward the Mentally Ill Changing?
Authors: IRVING ROOTMAN, HUGH G. LAFAVE
Journal: American Journal of Psychiatry (1969)

The authors compared the current attitude toward the mentally ill in a rural Canadian town with findings from a similar town in 1951. While noting a possible trend toward greater knowledge of mental illness and sophistication about it, they caution that attitudes expressed during an interview may not reflect actual behavior toward the mentally ill.
Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases
Authors: M. E. B. Roux, A. Florin-Christensen, R. M. Arana, D. Doniach
Journal: Gut (1974)

Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha<sub>1</sub>-fetoprotein, smooth muscle, and mitochondria. Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha<sub>1</sub>-fetoprotein in one. Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated. In three out of the 18 cases there was a double M-component. Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone.