tbuckley/cabot-search huggingface dataset:
Unilateral Renal Hemodynamics and Characteristics of Dye-Dilution Curves in Patients with Essential Hypertension and Renal Disease
Authors: J. MICHAEL KIOSCHOS, WALTER M. KIRKENDALL, MUCIO R. VALENCA, ANNETTE E. FITZ
Journal: Circulation (1967)

To gain information concerning cardiorenal hemodynamics in essential hypertension, renal vascular disease, and chronic glomerulonephritis, indocyanine green was used to determine renal blood flow (RBF), renal blood volume (RBV), mean transit time (MTT), appearance time (AT), buildup time (BT), and passage time (PT), in 83 kidneys of 47 hypertensive patients and eight volunteers. Cardiac output (CO) was concurrently measured. Dye, injected into the renal artery, while renal venous blood was drawn through a cuvette densitometer, gave a reproducible curve within 7.7%±2% with multi-exponential washout. RBF (dye) agreed closely (dye/PAH ratio=1.04) with para-aminohippurate (PAH) estimated renal blood flow in 18 kidneys. The RBF and RBV were significantly higher in patients with essential hypertension with high cardiac output than in those with normal cardiac output and were reduced significantly in patients with renal vascular diseases, although CO was the same. The contour of dye curves differed between the various diseases due to significant differences in BT and PT. AT and BT were significantly prolonged in patients with malignant hypertension, renal artery stenosis, and chronic glomerulonephritis. BT was significantly shorter in essential hypertensives than in normals. PT and MTT were significantly longer in malignant hypertensive, renal artery stenosis, and chronic glomerulonephritis groups. Passage time was significantly longer in glomerulonephritics than in nephrosclerotics. The procedure has value for the study of human renal circulation.
Quantification of regional myocardial blood flow in vivo with H215O.
Authors: S R Bergmann, K A Fox, A L Rand, K D McElvany, M J Welch, J Markham, B E Sobel
Journal: Circulation (1984)

Using H215O (half-life = 2.1 min) we demonstrated that a modification of the tissue autoradiographic approach permitted quantitation of myocardial blood flow in open-chest dogs by direct assay of myocardial tissue and that noninvasive estimation with positron-emission tomography (PET) delineated relative myocardial blood flow in intact dogs. In open-chest anesthetized dogs, the single-pass extraction fraction of H215O averaged 96 +/- 5% at flows of 80 to 100 ml/100 g/min. This high extraction fraction did not differ significantly over the range of 12 to 238 ml/100 g/min. Myocardial blood flow calculated after a 60 sec intravenous infusion of H215O and direct analysis of tissue correlated well with results obtained with microspheres (r = .94, n = 9 dogs). Subsequently the approach was adapted for preliminary use with PET. Estimation of myocardial content of radiolabeled H2O after intravenous infusion of 20 to 30 mCi of H215O was corrected for vascular pool radioactivity with the use of tomographic data obtained after administration of C15O by inhalation to label red blood cells. Tomograms obtained in vivo in six dogs with either normal or reduced regional blood flow correlated closely with the tomographically detectable distribution of 68Ga-labeled microspheres (r = .93) and with postmortem microsphere distribution (r = .95). The technique accurately reflects myocardial blood flow. With the use of PET, rapid sequential noninvasive estimation of relative regional myocardial blood flow has been demonstrated that should ultimately permit improved objective assessment of nutritional blood flow in patients in response to medical and surgical interventions designed to augment perfusion.
Insertion of permanent pacemakers as a day case procedure: Authors' reply
Authors: G. Haywood, A J. Camm, D. Ward
Journal: BMJ (1990)

treated with neutrons and photons.2Results were significantly better, however, for neutron than photon treatment in node positive patients, but worse in node negative patients with the suggestion that these were caused by inadequate planning because of the fixed neutron beams.No opposition was expressed to continued trials now under way.The discontinuation of funding suggested by Dr Tobias refers to that of new cyclotrons rather than of existing units.The arguments against neutrons have been well rehearsed.We still do not have clear cut answers.The proposed unit at St Thomas's would be for not only neutron therapy but also particle treatment of eye tumours and nuclide production for positron emission tomography.Cancer therapy depends on adequate planning of treatment obtainable only with the newer high energy neutrons.The earlier work at Hammersmith using fixed horizontal beams was a remarkable achievement, whatever the final value of neutron therapy.The real interest in this debate lies not only in the true role of neutron therapy but in the political machinations of the funding process.These have no long term significance.We await with interest the results of clinical trials and the evaluation of data obtained by positron emission tomography.
Labor Unions and Medical Care
Authors: I. S. Falk
Journal: New England Journal of Medicine (1964)

LABOR unions have a long history of concern for the health of their members and for security against the costs and losses that follow upon sickness and disability. The unions are now the largest group of organized consumers in the United States. Their increasing interest in health and their goals in matters of medical care are important not only for their own members but for society as a whole — because many union activities are pursued in a framework of community-wide services, and union policies and programs for their own members tend to set patterns for others as well.The . . .
Enalapril Does Not Enhance Exercise Capacity in Patients After Fontan Procedure
Authors: Amjad A. Kouatli, Jorge A. Garcia, Thomas M. Zellers, Ellen M. Weinstein, Lynn Mahony
Journal: Circulation (1997)

Background Angiotensin-converting enzyme inhibitors improve exercise capacity in adults with congestive heart failure by decreasing systemic vascular resistance and improving ventricular diastolic function. P atients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people. Methods and Results To test the hypothesis that afterload reduction therapy alters hemodynamic variables and augments exercise capacity in patients after a Fontan procedure, we compared the results of graded exercise with maximal effort from 18 subjects (14.5±6.2 years of age, 4 to 19 years after Fontan procedure) in a randomized, double-blind, placebo-controlled crossover trial using enalapril (0.2 to 0.3 mg · kg −1 · d −1 , maximum 15 mg). Each treatment was administered for 10 weeks. Diastolic filling patterns at rest were assessed by Doppler determination of the systemic atrioventricular valve flow velocity at the conclusion of each therapy. No difference was detected in resting heart rate, blood pressure, or cardiac index. Diastolic filling patterns were also similar. Exercise duration was not different (6.4±2.6 [enalapril] versus 6.7±2.6 minutes [placebo]). The mean percent increase in cardiac index from rest to maximum exercise was slightly but significantly decreased in subjects after 10 weeks of enalapril therapy (102±34% [enalapril] versus 125±34% [placebo]; P &lt;.02). At maximal exercise, cardiac index (3.5±0.9 [enalapril] versus 3.8±0.9 L · min −1 · m 2 [placebo]), oxygen consumption (18.3±9 [enalapril] versus 20.5±7 mL · min −1 · kg −1 [placebo]), minute ventilation (57.5±17 [enalapril] versus 55.4±19 L/min [placebo]), and total work (247±181 [enalapril] versus 261±197 W [placebo]) were not different. Conclusions We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.
Uncommon Malignant Tumors
Authors: S. Rosenthal
Journal: JAMA (1982)

In this compilation of 116 uncommon malignant neoplasms, Dr Antoniades has undertaken to provide "a more detailed, clearer understanding of all diseases involved" for the "maturing specialties of oncology." In this task, unfortunately, he has not succeeded. The idea behind this book is an excellent one. The inclusion of pathological descriptions, clinical features, treatment programs, and up-to-date references on a wide variety of unusual cancers under one cover could be of tremendous usefulness to the oncologist. Ordinarily, when confronted with a patient with an uncommon malignant tumor, the oncologist must spend several hours with the<i>Index Medicus</i>to ferret out previous experience with the disease in question. Dr Antoniades' book raises hope of a shortcut. That hope, however, remains unfulfilled. The book is divided into three sections: tumors of common histologies in unusual locations (eg, squamous cell carcinoma of the thyroid); tumors of uncommon histologies (eg, hemangiopericytoma, adenoid cystic carcinomas),
Rates of whole body protein synthesis and breakdown increase with the severity of inflammatory bowel disease.
Authors: J Powell-Tuck, P J Garlick, J E Lennard-Jones, J C Waterlow
Journal: Gut (1984)

Rates of whole body protein synthesis and breakdown were estimated in 19 undernourished patients with inflammatory bowel disease from the cumulative nine hour excretion of urinary 15NH3 after intravenous injection of 15N glycine. Thirty six studies were made during constant nutrient input either parenterally by 3 litre bag technique (29 studies), or enterally by nasogastric infusion of protein containing liquid feeds (four studies), or by diet kitchen prepared food eaten at two hourly intervals (three studies). Mean daily intakes were 50.7 kcal and 0.29 g nitrogen/kg body weight. Synthesis and break down rates correlated significantly with disease activity as judged by erythrocyte sedimentation rate and by ranking by an observer unaware of the turnover results. Rates for synthesis and breakdown by this method were about 2.1 and 1.7 g protein/kg/24 h respectively for ESR 10 increasing to 4.0 and 3.3 for ESR 100.
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245408 (XL147), an Oral Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors
Authors: Geoffrey I. Shapiro, Jordi Rodon, Cynthia Bedell, Eunice L. Kwak, Jose Baselga, Irene Braña, Shuchi S. Pandya, Christian Scheffold, A. Douglas Laird, Linh T. Nguyen, Yi Xu, Coumaran Egile, Gerald Edelman
Journal: Clinical Cancer Research (2013)

SAR245408 is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. This phase I study determined the maximum tolerated dose (MTD) of two dosing schedules [first 21 days of a 28-day period (21/7) and continuous once-daily dosing (CDD)], pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy.Patients with refractory advanced solid malignancies were treated with SAR245408 using a 3 + 3 design. Pharmacokinetic parameters were determined after single and repeated doses. Pharmacodynamic effects were evaluated in plasma, hair sheath cells, and skin and tumor biopsies.Sixty-nine patients were enrolled. The MTD of both schedules was 600 mg; dose-limiting toxicities were maculopapular rash and hypersensitivity reaction. The most frequent drug-related adverse events included dermatologic toxicities, diarrhea, nausea, and decreased appetite. Plasma pharmacokinetics showed a median time to maximum concentration of 8 to 22 hours, mean terminal elimination half-life of 70 to 88 hours, and 5- to 13-fold accumulation after daily dosing (first cycle). Steady-state concentration was reached between days 15 and 21, and exposure was dose-proportional with doses up to 400 mg. SAR245408 inhibited the PI3K pathway (∼40%-80% reduction in phosphorylation of AKT, PRAS40, 4EBP1, and S6 in tumor and surrogate tissues) and, unexpectedly, also inhibited the MEK/ERK pathway. A partial response was seen in one patient with advanced non-small cell lung cancer. Eight patients were progression-free at 6 months. Pharmacodynamic and clinical activity were observed irrespective of tumor PI3K pathway molecular alterations.SAR245408 was tolerable at doses associated with PI3K pathway inhibition. The recommended phase II dose of the capsule formulation is 600 mg administered orally with CDD.
Therapy in Lupus Erythematosus
Authors: JOHN R. HASERICK
Journal: Annals of Internal Medicine (1976)

Comments1 November 1976Therapy in Lupus ErythematosusJOHN R. HASERICK, M.D., F.A.C.P.JOHN R. HASERICK, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-5-681_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I am in agreement with Dr. Barnett (Ann Intern Med 84:610, 1976) in contradicting "the pessimistic impression placed on combination therapy" in lupus erythematosus. Immunosuppressive therapy in acute lupus erythematosus is impossible to use alone because its therapeutic efficacy is simply too delayed to be practical. In short, the patient is dead before the beneficial effect of this drug group could possibly be noticed. Thus, polypharmacy must be practiced, objectionable as it is.In our experience in treating lupus nephritis at the Cleveland Clinic, we learned quickly that nitrogen mustard, the drug we were interested in testing,...Reference1. KELLUMHASERICK RJ: Mechlorethamine therapy for systemic lupus nephropathy. Arch Dermatol 87:280-298, 1963 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1976Volume 85, Issue 5Page: 681-681KeywordsDrugsImmunosuppressivesLupus erythematosusLupus nephritis Issue Published: 1 November 1976 PDF DownloadLoading ...
X ray pictures in 88% of Michigan doctor's asbestosis diagnoses were found to be normal
Authors: F. Charatan
Journal: BMJ (2008)

All but one of 91 cases of asbestosis that were due to be heard in a Michigan court this month have been withdrawn by lawyers after the judge who was to hear the cases was shown evidence indicating that the doctor who made the diagnoses had got them wrong.

Michael Kelly, an occupational doctor in Lansing, Michigan, has worked for the past 15 years for the state of Michigan. In that time he diagnosed 7323 cases of asbestosis. In each case that he was asked to consider a possible diagnosis of asbestosis he was paid a fee of $500 (£335; €400) by …
Extent and Direction of Arterial Remodeling in Stable Versus Unstable Coronary Syndromes
Authors: Paul Schoenhagen, Khaled M. Ziada, Samir R. Kapadia, Timothy D. Crowe, Steven E. Nissen, E. Murat Tuzcu
Journal: Circulation (2000)

The morphological characteristics of coronary plaques in patients with stable versus unstable coronary syndromes have been described in vivo with intravascular ultrasound, but the relationship between arterial remodeling and clinical presentation is not well known.We studied 85 patients with unstable and 46 patients with stable coronary syndromes using intravascular ultrasound before coronary intervention. The lesion site and a proximal reference site were analyzed. The remodeling ratio (RR) was defined as the ratio of the external elastic membrane (EEM) area at the lesion to that at the proximal reference site. Positive remodeling was defined as an RR >1.05 and negative remodeling as an RR <0.95. Plaque area (13.9+/-5.5 versus 11.1+/-4.8 mm(2); P=0.005), EEM area (16.1+/-6.2 versus 13.0+/-4.8 mm(2); P=0. 004), and the RR (1.06+/-0.2 versus 0.94+/-0.2; P=0.008) were significantly greater at target lesions in patients with unstable syndromes than in patients with stable syndromes. Positive remodeling was more frequent in unstable than in stable lesions (51. 8% versus 19.6%), whereas negative remodeling was more frequent in stable lesions (56.5% versus 31.8%) (P=0.001).Positive remodeling and larger plaque areas were associated with unstable clinical presentation, whereas negative remodeling was more common in patients with stable clinical presentation. This association between the extent of remodeling and clinical presentation may reflect a greater tendency of plaques with positive remodeling to cause unstable coronary syndromes.
GSK executives admit to bribery and tax crimes, China claims
Authors: J. Parry
Journal: BMJ (2013)

Some senior executives working for GlaxoSmithKline in China have confessed to “serious economic crimes,” the country’s security ministry said in a statement on Thursday.

The ministry, which has been investigating Chinese subsidiaries of the UK based drug firm in recent weeks, said it had detained the executives as well as a number of travel agency staff, who …
Clinical trials to begin on potent angiogenesis inhibitors
Authors: K. Abbasi
Journal: BMJ (1998)

Two new drugs that inhibit the blood supply to tumours are to undergo clinical trials in humans. A statement by the US National Cancer Institute that research on endostatin and angiostatin is “a high priority” sent the share price of the manufacturer of the drugs, Entremed, soaring and caused massive public interest.

In one day …
Bronchiolitis obliterans in systemic lupus erythematosus.
Authors: D R Porter
Journal: Annals of the Rheumatic Diseases (1992)

cance rating of one.The combinations of NSAIDs with a fi blocker, quinidine with cimetidine, and glibenclamide with a thiazide diuretic each occurred in one patient.These combinations have a significance rating of two.The combinations of NSAIDs with methotrexate, salicylates with enalapril, and digoxin with hydroxychloroquine each occurred in two patients.These combinations have a significance rating of four.None of the patients had reported a drug interaction before admission.The mean duration of admission was 39 days (range 7-84), during which time the only adverse reactions were diarrhoea secondary to auranofin in one patient and a skin rash secondary to sodium aurothiomalate in one patient.This small study supports previous studies illustrating the potential for drug interactions in patients with arthritis and emphasises the need for continued vigilance.Most potential drug interactions involve NSAIDs.'The absence of significant clinical drug interactions might be attributed to the judicious use of NSAIDs.They were reserved for the management of definite inflammation, and of the 33 patients receiving NSAIDs, 22 were receiving half the maximum recom- mended dose.
The DNA revolution in population genetics
Authors: Luca L Cavalli-Sforza
Journal: Trends in Genetics (1998)

Unprecedental clarity has come to our understanding of genetic variation by the analysis of DNA sequences. It is not surprising that the new DNA technologies are leading to a resurgence of interest in population genetics. In this review, I discuss recent progress and future directions towards reconstructing the history of human populations. There is increasing consensus on a recent 'Out of Africa' origin of modern humans, which explains why the greatest fraction of genetic diversity is found within populations, rather than between them. The comparison of Y chromosome and mitochondrial DNA data shows remarkable sex differences in geographic variation. The analysis of Neanderthal DNA has been a major breakthrough in the study of fossil DNA. Among major hopes for the future are application to polygenic diseases.
Progress in the wrong direction
Authors: J A Hicklin
Journal: BMJ (1991)

selective damage to specific cell populations has not occurred.Analysis of incorporated bromodeoxyuridine with monoclonal antibodies requires the DNA to be denatured (commonly by exposure to acid).Unfortunately, this step is inherently prone to error as it leads to considerable cell loss and possible damage to antigenic sites.Also, sensitivity to DNA denaturation varies across the cell cycle4for example, cells fixed in late S phase will have more denatured DNA.Our experience in colorectal tumour tissue has shown that labelling indices obtained with both flow cytometry and immunohistochemistry results in reproducible variations that are dependent on acid concentration.The intention of this letter is not to discourage the use of thymidine analogues in cell proliferation analysis but simply to make interested parties aware of the inherent caveats in this methodology.Advances in the clinical application of bromodeoxyuridine will depend on a closer investigation of these enigmas at a tissue specific level.The desire for data should not tempt us to explain the answers before we have asked the questions.
Raising boys to maintain armies
Authors: R. Mazali
Journal: BMJ (1995)

Jewish Israeli boys are made aware of their future role as warriors from early childhood. Their entire development is oriented towards it. Older men promise and threat simultaneously, “Wait and see, when you get to the army.…” After scraping their knees little boys are told, “It'll pass before the army,” while girls are told, “It'll pass before the wedding.”

Such messages and the ritual aspect of military service are reinforced by the secrecy surrounding military matters. This establishes a privileged inner circle, to be joined only via army service.

As women's military duty is fundamentally different from that of men in Israel, they are among those excluded from the privileged core. Men's service defines masculinity as lethal strength. The boy soldier is given a gun, literally the power to kill. One man interviewed for a film that I worked on was bemused to sense a joy of the hunt during service. Another, whose son …
Hemolytic anemia associated with lead poisoning from shotgun pellets and the response to succimer treatment
Authors: Mahmoud H. Aly, Hugh C. Kim, Stephen W. Renner, Andrew Boyarsky, Martin Kosmin, Donald E. Paglia
Journal: American Journal of Hematology (1993)

Abstract Symptomatic lead poisoning with severe hemolytic anemia was observed in a patient with retained shot gun pellets. Surgical resection of the retained pellets and the use of a newer chelating agent, Succimer (2,3‐dimercaptosuccinic acid) successfully lowered blood lead level. Hemolytic anemia was associated with deficient erythrocyte pyrimidine 5′‐nucleotidase, and lowering of the lead level corrected the deficiency, suggesting that the enzyme deficiency is responsible for the hemolysis associated with lead poisoning. This case illustrates that retained lead pellets from shotgun wounds can cause severe lead poisoning. © 1993 Wiley‐Liss, Inc.