tbuckley/cabot-search huggingface dataset:
Immunohistochemical study of hepatic fibrosis induced in rats by multiple galactosamine injections
Authors: Mieke A. Jonker, Freke W. J. Dijkhuis, Machiel J. Hardonk, Peter Moerkerk, Joop Ten Kate, Joris Grond
Journal: Hepatology (1994)

Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140 intraperitoneal injections of D-galactosamine (500 mg/kg body wt, three times weekly). Controls received injections of saline solution. Cryostat sections of liver tissue obtained on biopsy or autopsy were immunostained with a panel of monoclonal and polyclonal monospecific antibodies reactive with macrophages, T and B lymphocytes, desmin, the extracellular matrix components fibronectin; laminin; collagen types I, III and IV; and the fibronectin receptor α5β1. Total RNA was extracted and Northern-blot analysis was performed with a specific cDNA probe for rat collagen type III. Spotty liver cell necrosis and mild portal and parenchymal inflammation was seen after 10 injections of galactosamine. After 20 to 40 injections, expansion of portal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of cirrhosis at later intervals. These progressive histological changes were paralleled by a gradual increase of desmin-positive cells in developing septa with deposition of fibronectin; collagen types I, III and IV; and laminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of mRNA for collagen type III. In conclusion, repetitive administration of galactosamine causes progressive liver disease with prominent bile ductule proliferation and development of fibrous septa. These pathological alterations bear some resemblance to the morphological changes in chronic biliary disease in human beings. (Hepatology 1994;19:775-781).
Effect of protein intake on regional vascular resistance and reactivity to angiotensin II in the rat.
Authors: B M Murray
Journal: Circulation Research (1990)

Male Sprague-Dawley rats (200-250 g) were fed low protein (6%) diets (LP rats), high protein (50%) diets (HP rats), or regular rat chow (approximately 16% protein) (control rats) and studied under anesthesia after 2 weeks. Dietary protein intake did not affect mean arterial pressure, but renal blood flow was increased in the HP rats and decreased in the LP rats compared with the control rats. Mesenteric blood flow was not significantly different in the three diet groups. Captopril (10 mg.kg-1 i.v.) had no effect on renal vascular resistance in the HP rat but did reduce the elevated renal vascular resistance seen in the LP rat. Meclofenamate (5 mg.kg-1 i.v.) did not significantly affect renal hemodynamics in either HP or LP rats. Finally, the HP rat exhibited resistance to the systemic pressor, renal, and mesenteric vasoconstrictor effects of angiotensin II. Captopril restored the systemic pressor and the mesenteric vasoconstrictor response but not the renal vasoconstrictor response to angiotensin II. Meclofenamate, on the other hand, restored both the systemic pressor response and the renal vasoconstrictor response. Thus, in the LP rat, the vascular response to angiotensin II remains intact, and renal vasoconstriction appears to be mediated by angiotensin II. In contrast, in the HP rat, the renovascular response to angiotensin II is blunted apparently because of enhanced renal prostaglandin production. However, neither increased renal prostaglandin synthesis nor blunting of the renovascular response to angiotensin II appears to account for the chronic vasodilation seen in the HP rat.
Sex Chromatin in Women With Breast Cancer, Leukemia, Lymphoma, and Hypertension
Authors: Alex S. D. Spiers
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Some constitutional disorders associated with aneuploidy and other cytogenetic defects carry an increased risk of neoplastic disease.<sup>1</sup>Numerical abnormality of the sex chromosomes, the commonest constitutional aneuploidy in adults, is no exception. The XXY Klinefelter's syndrome is associated with an enhanced risk of leukemia, lymphoma, and breast cancer,<sup>2</sup>and the XO Turner's syndrome may have an association with leukemia. The XXX syndrome may be associated with an increased liability to mental illness,<sup>3</sup>and the coexistence of X-trisomy and Hodgkin's disease has been observed,<sup>4</sup>but there does not seem to be an overall increased incidence of cancer in XXX women. A survey of 8,600 consecutive hospital admissions disclosed seven XXY men and three XXX women but showed no new disease associations of X chromosome abnormalities: one XXY man had carcinomatosis with an unknown primary tumor.<sup>5</sup> By staining the nuclei of buccal mucosal cells
Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus
Authors: A Melander, G Sartor, E Wahlin, B Schersten, P-O Bitzen
Journal: BMJ (1978)

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.
The TRAIL to arthritis
Authors: George C. Tsokos, Maria Tsokos
Journal: Journal of Clinical Investigation (2003)

Antigen-specific lymphocytes are involved in synovial proliferation within inflamed joints. Activated lymphocytes and synoviocytes from patients with rheumatoid arthritis express receptors that can bind TNF-related apoptosis-inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen and transduced with an adenovirus-based vector able to express TRAIL limit the incidence of arthritis in a model of collagen-induced arthritis and joint inflammation. These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases.
Evolutive Profile Of Iga Deficiency Patients From A Pediatric Brazilian Reference Center For Primary Immunodeficiency
Authors: M.B. Dorna, M.T. Iwashita, D.G.C. Rezende, L.A. Watanabe, M.D. Asanuma, A.C. Pastorino, A.P.B.M. Castro, A.B.F. Fomin, M.M.S. Carneiro-Sampaio, C.M.A. Jacob
Journal: Journal of Allergy and Clinical Immunology (2010)

RATIONALE: To describe the clinical features of IgA deficiency (IgAD) patients followed at a pediatric Brazilian reference center for primary immunodeficiency (PID). METHODS: Retrospective study from 81 patients (1,02M: 1F) diagnosed with IgAD (IUIS criteria) and followed at Allergy and Immunology Unit - Faculdade de Medicina - Universidade de São Paulo in the last 27 years. Clinical features and laboratorial data were evaluated. RESULTS: Median time of follow-up was 6,2y. Age at the diagnosis varied from 4 to 18,7 years (median = 6,8y). Concerning the reasons for investigating IgAD it was found: recurrent infections in 55,5%, allergic diseases in 14,8%, autoimmunity in 8,6%, severe or complicated infections in 7,4% and familial history of IgAD in 5% of patients. Infections detected during follow up were: upper respiratory tract infection (76,5%, 1-37 episodes/patient), pneumonia (60,5%), skin and subcutaneous infection (19,9%) and other infections in 14,8%. Giardiasis was diagnosed in 18,5% patients, followed by ascaridiase in 7,4%. Allergic diseases were observed 75,3%, and auto-immunity in 13,5%. Eleven patients referred at least one family member with IgAD (nine different families) and 6, familial history for auto-immunity. One mother's patient had CVID. Regarding the laboratorial evolution, 4 patients presented normalization of the IgA levels (median age 18,1y) and 14 showed elevation of IgA levels (IgA>7mg/dl but <p3 for the age). One patient developed CVID at the age of 12,7y. CONCLUSION: Patients with IgA deficiency demand long term follow-up due to the possibility of various clinical and laboratorial evolutions with different degrees of immunological impairment and the development of autoimmunity.
Vaccination Against Measles in General Practice
Authors: A. P. Goffe, J. T. Woodall, E. Tuckman, J. D. Paulett, I. N. Manser, L. M. Franklin, P. A. L. Chapple
Journal: BMJ (1963)

While these last two studies were in progress it became apparent that an epidemic of measles was developing in England, and it was decided to carry out a study of the use of live measles vaccine in general practice.The objects of the study were to observe the protective effect of the vaccine in pre-school children living in families where the degree of exposure to natural measles could be assessed, and to record reactions to the vaccine. Materials and MethodsPlan of the Trial.-Inorder to obtain an adequate number of home exposures to measles in vaccinated children, families were selected which had at least two children-one of pre-school age and one of primary- school age.After setting one-third of all families on one side as controls, vaccination was offered to the remaining families for the pre-school children only.The older school-age children were left unvaccinated in the anticipation that they would develop measles by contact with cases at school.They would then provide a natural challenge of the immunity of the pre-school children at home, and a comparison would be possible of the incidence of measles in home-exposed vaccinated and control populations.Vaccine.-The measles vaccine consisted of living attenuated measles virus, Edmonston strain (Enders et al., 1962).Only one batch, MV-3C, was used, the preparation and testing of which has been described in detail previously (Goffe and Laurence, 1961).The freeze-dried vaccine was reconstituted with 1 ml. of sterile distilled water immediately before use and was injected subcutaneously.Study Population and Allocation to Groups.-Thechildren in this study were patients of a partnership of six doctors, and nearly all of them lived on a housing estate on the outskirts of London.Each doctor's list was searched for families containing at least one child born between January 10, 1956, and July 1, 1960 (pre- school age), and another born between September 1,
And for my next trick
Authors: W. Moore
Journal: BMJ (2008)

In the laudable history of clinical trials, little has given doctors more pleasure than the demonstration of the placebo effect, particularly when it is used to undermine unorthodox treatments.

John Hunter, the tireless 18th century experimenter, could scarcely conceal his delight when conducting a trial on the popular folklore remedy of spider’s web. After secretly dosing a patient who had the “ague” with the treatment, he found that it had “not the slightest effect”; yet once his patient had been informed of the intervention, “the effect was produced,” he gloated.

As a maverick who regarded conventional and alternative treatments with almost equal disdain, Hunter was one of the few—and possibly the first—to test a standard medicine against a placebo. Convinced that mercury, the stock treatment for gonorrhoea, was …
Regression of Colorectal Adenomas With Intravenous Cytotoxic Chemotherapy in a Patient With Familial Adenomatous Polyposis
Authors: Douglas H. Jones, Peter T. Silberstein, Henry Lynch, Charles Ternet
Journal: Journal of Clinical Oncology (2005)

1021 Background Familial adenomatous polyposis (FAP) is an autosomally dominant disease. This is a case of a 45 year old woman with FAP and colorectal cancer who showed marked regression of polyps after intravenous chemotherapy. Methods Using PubMed and MEDLINE we searched all citations in English available from 1966 to the present. Search terms included polyps, regression, chemotherapy, colorectal adenomas, and polyposis. Results The patient's colonoscopy in June 2002 revealed hundreds of colorectal adenomas throughout her colon. In June 2002, she had a left hemicolectomy and an liver biopsy. The pathology showed tubular adenomas with metastatic disease in the pericolonic lymph nodes and liver (Stage IV, T3N1M1). Her APC gene test was positive in April 2003. From 9/30/02 to 4/8/03 the patient received 5 cycles of bolus 5-FU, leucovorin, and irinotecan. A colonoscopy on 2/3/03 demonstrated reduced number and size of polyps compared to her prior colonoscopy. Ultrasounds of the liver on 9/25/02 and 11/5/02 ...
In Defense of the Drug Research Board
Authors: Daniel L. Azarnoff
Journal: JAMA (1975)

ANTISUBSTITUTION laws were adopted by most states after World War II to prevent the dispensing of counterfeit drugs to patients. These laws have served their purpose well. Recently, however, there have been attempts to repeal or at least to modify these laws to allow the pharmacist's selection of the drug product to be dispensed. Several states have already modified their laws to allow such substitution. The rationale for these modifications is that the pharmacist is the member of the health care team most knowledgeable about biopharmaceutics and, therefore, the best equipped to make this type of decision. The pharmacist, as demonstrated in a recent study,<sup>1</sup>is capable of utilizing bioavailability data in a manner similar to experts. The problem, however, is more complex. On Oct 25, 1974, the Drug Research Board of the National Research Council passed a resolution, which was subsequently approved by the Assembly of Life Sciences
Regional alveolar pressure during periodic flow. Dual manifestations of gas inertia.
Authors: J L Allen, I D Frantz, J J Fredberg
Journal: Journal of Clinical Investigation (1985)

We measured pressure excursions at the airway opening and at the alveoli (PA) as well as measured the regional distribution of PA during forced oscillations of six excised dog lungs while frequency (f[2-32 Hz]), tidal volume (VT [5-80 ml]), and mean transpulmonary pressure (PL [25, 10, and 6 cm H2O]) were varied. PA's were measured in four alveolar capsules glued to the pleura of different lobes. The apex-to-base ratio of PA's was used as an index of the distribution of dynamic lung distension. At low f, there was slight preferential distension of the lung base which was independent of VT, but at higher f, preferential distension of the lung apex was found when VT's were small, whereas preferential distension of the lung base was found when VT's approached or exceeded dead space. These VT-related changes in distribution at high frequencies seem to depend upon the branching geometry of the central airways and the relative importance of convective momentum flux vs. unsteady inertia of gas residing therein, which, in this study, we showed to be proportional to the ratio VT/VD*, where VD* is an index of dead space. Furthermore, they imply substantial alteration in the distribution of ventilation during high frequency ventilation as f, VT, and PL vary. The data also indicate that alveolar and airway opening pressure costs per unit flow delivered at the airway opening exhibit weakly nonlinear behavior and that resonant amplification of PA's, which has been described previously for the case of very small VT's, persists but is damped as VT's approach dead space values.
Biodegradable polymeric microparticles for drug delivery and vaccine formulation: the surface attachment of hydrophilic species using the concept of poly(ethylene glycol) anchoring segments
Authors: A.G.A. Coombes, S. Tasker, M. Lindblad, J. Holmgren, K. Hoste, V. Toncheva, E. Schacht, M.C. Davies, L. Illum, S.S. Davis
Journal: Biomaterials (1997)
Longevity in the Tetralogy of Fallot
Authors: H. Meindok
Journal: Thorax (1964)

The congenital abnormality of the heart consisting of pulmonary stenosis, ventricular septal defect, and an overriding aorta was described in 1673 by the Danish scholar, Nicolas Stensen (Warburg, 1942).Fallot's (Fallot, 1888) description included right ventricular hypertrophy as an essential part of the malformation.Stensen had made no mention of this, possibly because he reported on the heart of the foetus.Maud Abbott (1936) found in her series of 1,000 cases of congenital heart disease that the average life expectancy in Fallot's tetralogy was 12 years, and only six years in cases with pulmonary artery atresia.In one report on 200 living patients (Donzelot, de Balsac, Emam-Zade, Escalle, and Metianu, 1949) with Fallot's tetralogy, 13 were between the ages of 21 and 30 years and only one over the age of 40.In another report (Soulid, Vernant, Andreuzzi, and Magnoli, 1956) on 144 cases of this malformation, there were eight patients between the ages of 20 and 30, two between 30 and 40, and only two over the age of 40 years.Since the famous case of a musician, reported by White and Sprague (1929), who died in his sixtieth year, 26 other cases have been reported with a survival of more than 40 years.There were four patients between 60 and 70 years (Bain,
Epidemiology of Vibrio cholerae 0139 with special reference to intrafamilial transmission in Calcutta
Authors: P.G. Sengupta, B.K. Sircar, S.K. Mandal, A.K. Mukhopadhyay, G.B. Nair, D.N. Gupta, S. Ghosh, N.C. Saha, B.C. Deb, S.N. Sikder, B. Manna, S.K. Bhattacharya, S.P. De, B.K. Mandal
Journal: Journal of Infection (1995)
Extracellular Matrix and Oscillatory Mechanics of Rat Lung Parenchyma in Bleomycin-induced Fibrosis
Authors: MARISA DOLHNIKOFF, THAIS MAUAD, MARA S. LUDWIG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We investigated in vivo and in vitro oscillatory mechanics in bleomycin-induced fibrotic lungs and correlated these with morphometric changes in the collagen-elastin matrix and contractile cells. Fischer rats received bleomycin sulfate (BLEO,1.5 U) or saline intratracheally. Four weeks later tracheal flow and tracheal and alveolar pressure (using alveolar capsules) were measured in open-chested rats during mechanical ventilation (V˙ t = 8 ml/kg, f = 1 Hz, PEEP = 4 cm H2O). Total lung, tissue, and airway resistance (R) and lung elastance (E) were calculated. In addition, excised parenchymal strips (10 × 2 × 2 mm) were studied in the organ bath. Strips were attached to a force transducer at one end and to a servo-controlled lever arm that effected length (L) changes at the other. Sinusoidal oscillations were applied (f = 1 Hz, amplitude = 2.5% resting L and tension = 0.7 g) and R, E, and hysteresivity ( η ) were calculated. Strips were then exposed to acetylcholine (ACh, 10− 3 M). The amount of collagen and elastic fibers in the parenchymal strip was assessed semiquantitatively by point-counting in 5- μ m-thick sections stained with either Sirius Red or Weigert's Resorcin-fuchsin. α -Smooth-muscle-specific actin was detected immunohistochemically. Both in vivo and in vitro, R, E, and η were significantly increased in BLEO rats (p < 0.05). The % increase in R, E and η after Ach was greater in BLEO rats (p < 0.01). There was also a significant increase in the volume proportion of collagen, elastic fibers, and actin in the parenchyma (p < 0.01). In BLEO rats, baseline R and E were correlated with the volume proportion of collagen in the parenchyma. We conclude that changes in the collagen-elastin matrix contribute to changes in the viscoelastic properties of bleomycin-treated rat lungs. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis.
Mini-Internships: An Experience in Health-Care Delivery for Community Leaders
Authors: Ralph Crawshaw, William Zieverink, Collette Wright
Journal: New England Journal of Medicine (1983)

A number of lay leaders, including legislators, public officials, administrators, business executives, judges, reporters, and the trustees of philanthropic foundations, substantially influence health-policy decisions. Although a few lay leaders have had coincidental involvement with clinical medicine, most experience medical service only as patients or the relatives of patients. Concerned with the lack of clinical perspective displayed by lay leaders in the determination of city and state health policies, one of us (R.C.), while president of the Multnomah County Medical Society in Portland, Oregon, initiated a series of integrated "white coat" experiences, called the Mini-Internship Program, for recognized civic leaders in . . .
Boston and New England in 1812
Authors: Henry F. Howe
Journal: New England Journal of Medicine (1962)

IN the year of the founding of the New England Journal of Medicine and Surgery, 1812, Boston was not even at the threshold of that intellectual Golden Age which was soon to place her at the very pinnacle of American literature. Ralph Waldo Emerson once blandly asserted: "From 1790 to 1820 there was not a book, a speech, a conversation, or a thought in the state of Massachusetts." In 1791 Brissot de Warville, the French revolutionary leader, said of Boston: "The university certainly contains men of worth and learning, but science is not diffused among the inhabitants of the . . .
Length of Survival With Brain Metastases-Reply
Authors: Nicholas J. DiBella
Journal: JAMA (1981)

<h3>In Reply.—</h3> The main point of Dr Mira's letter is that patients with small cell carcinoma of the lung have a greater tendency to have brain metastases develop with increasing length of survival. We agree with this statement and expressed this in our article. Our article states that the present aggressive regimens may result in an improved survival and, therefore, an increase in the incidence of brain metastases. This hypothesis was based on our finding that those patients who lived longer had an increased incidence of brain metastases. We then quoted Hansen who had similar findings and conclusions. Perhaps instead of stating that "patients who developed brain metastases had a longer survival," any misinterpretation could have been prevented if we had simply stated that those patients who survived longer had a greater tendency to have the development of brain metastases. We do agree with the comments by Dr Mira on