tbuckley/cabot-search huggingface dataset:
Synergy between Natriuretic Peptides and Phosphodiesterase 5 Inhibitors Ameliorates Pulmonary Arterial Hypertension
Authors: Reshma S. Baliga, Lan Zhao, Melanie Madhani, Belen Lopez-Torondel, Cristina Visintin, David Selwood, Martin R. Wilkins, Raymond J. MacAllister, Adrian J. Hobbs
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Phosphodiesterase 5 (PDE5) inhibitors (e.g., sildenafil) are selective pulmonary vasodilators in patients with pulmonary arterial hypertension. The mechanism(s) underlying this specificity remains unclear, but studies in genetically modified animals suggest it might be dependent on natriuretic peptide bioactivity.Objectives: We explored the interaction between PDE5 inhibitors and the natriuretic peptide system to elucidate the (patho)physiological relationship between these two cyclic GMP (cGMP)-regulating systems and potential of a combination therapy exploiting these cooperative pathways.Methods: Pharmacological evaluation of vascular reactivity was conducted in rat isolated conduit and resistance vessels from the pulmonary and systemic circulation in vitro, and in anesthetized mice in vivo. Parallel studies were undertaken in an animal model of hypoxia-induced pulmonary hypertension (PH).Measurements and Main Results: Sildenafil augments vasodilatation to nitric oxide (NO) in pulmonary and systemic conduit and resistance arteries, whereas identical vasorelaxant responses to atrial natriuretic peptide (ANP) are enhanced only in pulmonary vessels. This differential activity is mirrored in vivo where sildenafil increases the hypotensive actions of ANP in the pulmonary, but not systemic, vasculature. In hypoxia-induced PH, combination of sildenafil plus the neutral endopeptidase (NEP) inhibitor ecadotril (which increases endogenous natriuretic peptide levels) acts synergistically, in a cGMP-dependent manner, to reduce many indices of disease severity without significantly affecting systemic blood pressure.Conclusions: These data demonstrate that PDE5 is a key regulator of cGMP-mediated vasodilation by ANP in the pulmonary, but not systemic, vasculature, thereby explaining the pulmonary selectivity of PDE5 inhibitors. Exploitation of this mechanism (i.e., PDE5 and neutral endopeptidase inhibition) represents a novel, orally active combination therapy for pulmonary arterial hypertension.
Hepatic Injury Caused by <i>L</i> -Alpha-Methyldopa
Authors: S. G. ELKINGTON, W. M. SCHREIBER, H. O. CONN
Journal: Circulation (1969)

L -alpha-methyldopa (Aldomet)-induced liver disease is a relatively mild and uncommon complication of therapy with this drug. Most commonly it is characterized by a rise in serum alkaline phosphatase, glutamic oxaloacetic transaminase levels, and increased Bromsulphalein retention. Elevation of the serum bilirubin may occur. In its most benign form the condition is usually symptomless, but complaints, such as anorexia, abdominal pain, or pruritus, and signs, such as fever or hepatomegaly, may occur. Histologic changes similar to those of viral hepatitis have been observed. The condition is usually benign and remits on withdrawal of the drug. Progressively more mild exacerbations on readministration of the drug suggest that desensitization may be possible in patients who exhibit hepatic abnormalities. Its low and sporadic incidence is typical of a hypersensitivity reaction. It is suggested that routine liver function tests should be undertaken at intervals during therapy. The occasional occurrence of Aldomet-induced liver disease is no contraindication to the use of this antihypertensive agent.
Comment on: Bergenstal et al. A Randomized, Controlled Study of Once-Daily LY2605541, a Novel Long-Acting Basal Insulin, Versus Insulin Glargine in Basal Insulin–Treated Patients With Type 2 Diabetes. Diabetes Care 2012;35:2140–2147
Authors: Philip D. Home
Journal: Diabetes Care (2013)

It was good to see the interesting article by Bergenstal et al. (1), from both academic and commercial colleagues, of a novel approach to a long-acting insulin (LY2605541), possibly hepatospecific, as studied in individuals with type 2 diabetes. Both alanine aminotransferase (ALT) and serum triglycerides were higher compared with a standard insulin comparator, whereas body weight trajectory was …
Imaging of Vascular Graft Infection with Tc-99m WBC.
Authors: S. Dadparvar, C. I. Kaufman, J. Wang, K. M. Kapadia, M. M. Gillan, L. Krishna, W. J. Slizofski, T. Matsumoto
Journal: Clinical Nuclear Medicine (1997)

Dadparvar, S.; Kaufman, C. I.; Wang, J.; Kapadia, K. M.; Gillan, M. M.; Krishna, L.; Slizofski, W. J.; Matsumoto, T. Author Information
Natural history of the HBsAg carrier.
Authors: M G Anderson, I M Murray-Lyon
Journal: Gut (1985)

Progress reportNatural history of the HBsAg carrier Chronic carriage of the hepatitis B virus (defined as carriage longer than six months) is an important cause of morbidity and mortality worldwide but particularly in Africa and the Far East.Some idea of the scale of the problem can be gauged from the fact that there are estimated to be 800 000 carriers in USA alone and 200 million carriers worldwide.There are said to be 4000 deaths per annum in the USA due to HBsAg positive cirrhosis and up to 250 0001 deaths per annum from HBsAg positive hepatocellular carcinoma throughout the world. Modes of transmissionIn Africa and the Far East where the prevalence of infection in the community is high (10-15% population), the virus is usually spread from mother to infant shortly after birth and between children in the first few years of life.2 3 Such early infection is usually asymptomatic and chronic carriage of the virus frequently results.In Western Europe and the USA as examples of areas of low prevalence of HBsAg carriage, infection usually occurs in adult life and is related to either contact with infected blood or blood products in a health care setting or to drug addiction.4There is an increased incidence of infectiop among household contacts of chronic carriers of hepatitis B,5 and sexual contact, either heterosexual or between male homosexuals, has been increasingly recognised as an important route of transmission.4 6This latter route may be more prone to result in chronic liver disease.7The majority of infections in adults whatever the source are inapparent and perhaps only 30-40% patients become jaundiced.8 Factors favouring chronicityA number of factors seem to favour the development of a chronic carrier state.These include infection in infancy or childhood (see above) and male gender.Chronicity also tends to follow mild anicteric illness rather than a severe attack with deep jaundice9 and this state of affairs may be more likely with a small viral inoculum.10Approximately 10% of patients with clinically apparent acute hepatitis B can be expected to become chronic carriers.11Impairment of cell mediated immune responsiveness at the time of infection has been held to account for the tendency to chronicity found in patients with Down's syndrome, chronic renal failure, leukaemia, and on corticosteroid therapy.12In a prospective study among cancer patients inadvertently exposed to HBV, however, there was no increased likeli- hood of patients becoming chronic carriers.This was true even for those patients who were receiving immunosuppressive therapy. 13Several immunological mechanisms favouring the development of chronicity have been postulated.14
Postprandial thrombin activatable fibrinolysis inhibitor and markers of endothelial dysfunction in type 2 diabetic patients
Authors: Mercedes Rigla, Ana Maria Wägner, Montserrat Borrell, José Mateo, Jordi Foncuberta, Alberto de Leiva, Jordi Ordóñez-Llanos, A. Pérez
Journal: Metabolism (2006)
Kidney function after renal arterial embolism
Authors: J. N. Fergus, N. F. Jones, M. L. Thomas
Journal: BMJ (1969)

Seven patients with atrial fibrillation had acute unilateral renal pain associated with suppression of function in the affected kidney. This was ascribed to renal embolism. Arteriography performed in four patients showed abnormalities in the renal arterial tree in three, though thrombus in a main artery was present in only one. Considerable function returned spontaneously to the affected kidney in six patients as judged by intravenous pyelography or renography. In two patients the sole functioning kidney was affected, leading to acute oliguric renal failure, but renal function recovered in each case. The routine use of anticoagulants in persistent atrial fibrillation is justified by such cases.
Mongolism in a Twin
Authors: J. V. Morris
Journal: BMJ (1957)

SEROTYPES MBRImJOURN4LIt was noticed that the earlier in life these babies were infected the milder was the infection (see Fig. 2).8 0 DAYS AFTER BIRTH a 2 3 4 5 6 7 8 9 io 1 12 6 4 < t o m 2 - UI. 0 cc z 2 =~~~~~~~~~~,TOXAEMIC 4 -Tx = ~~~~~~ENTERiTIS-4 ENTERITIS CARRIERS AND BABIES WITH 6s | ONLY ABNORMAL STOOLS FIG.2.-Severity of infection. Conclusion and SummaryIt can be assumed that in the maternity clinics, where child-bearing mothers are assembled, the possibility of infection with pathogenic E. coli types exists in just the same way as between infants in the infant wards.The transmission of these pathogenic germs may be from infant to infant through the nurses and other medical staff.In the same way, the mother may be infected by the nursing or medical staff.The latter possibility, if perhaps not frequent, is still of epidemiological import- ance; for the mother, who will in the future nurse the baby, leaves the hospital carrying the infection with her.Furthermore, we may assume the possible transmission of pathogenic E. coli serotypes from mother to child in all phases of delivery and after.-The relatively high percentage of positive isolations of E. coli serotypes obtained from babies born at home suggests that not all their mothers could have been in- fected in hospital.This does not detract from the importance of the clinical infective chain suggested in this communication.The results of these investigations show the urgent need of an increased stress on prophylaxis.This will mean intensive instruction of the nurses and medical staff, and bacteriological control of all their work in hospital (Ocklitz, 1956).At home such prophylaxis is more difficult to attain.It is evident that our pro- phylactic efforts in and outside the hospital may be useful not only in controlling infections such as infantile diarrhoea, but also in combating all other infections, especially those caused by strains of staphylococcus.REFERENCES
Comparison between laparoscopic sterilization and tubal ligation.
Authors: G Hughes, W A Liston
Journal: BMJ (1975)

During 1970-3, 1910 laparoscopic sterilizations and 531 tubal ligations were performed in Aberdeen. Common complications occurred with 61 (3.2%) and 99 (18.6%) of the operations respectively, but the pregnancy rate was much higher (2.2%) after laparoscopic sterilization.
Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer
Authors: Susumu Sakata, Djamel Lebeche, Yuri Sakata, Naoya Sakata, Elie R. Chemaly, Li Fan Liang, Prabhu Padmanabhan, Noboru Konishi, Miyako Takaki, Federica del Monte, Roger J. Hajjar
Journal: Molecular Therapy (2006)

The Otsuka-Long-Evans Tokushima Fatty rat represents a model for spontaneous non-insulin-dependent type II diabetes mellitus (DM), characterized by diastolic dysfunction and associated with abnormal calcium handling and decrease in sarcoplasmic reticulum Ca2+ -ATPase (SERCA2a) expression. The aim of this study was to examine whether SERCA2a gene transfer can restore the energetic deficiency and left ventricular (LV) function in this model. DM rats were randomized to receive adenovirus carrying either the SERCA2a gene (DM + Ad.SERCA2a) or the beta-galactosidase gene (DM + Ad.betaGal) or saline (DM + saline). LV mechanoenergetic function was measured in cross-circulated heart preparations 3 days after infection. In DM, end-systolic pressure at 0.1 ml intraballoon water (ESP0.1) was low and end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) was high (22 mm Hg), compared with non-DM (EDP0.1 12 mm Hg). In DM + Ad.SERCA2a, however, ESP0.1 was increased over 200 mm Hg and EDP(0.1) was decreased to 7 mm Hg. LV relaxation rate was fast in DM + Ad.SERCA2a, but slow in the other DM groups. There was no difference in relation between cardiac oxygen consumption per beat and systolic pressure-volume area among all groups. Finally, the oxygen cost of LV contractility in DM was about three times as high as that of normal. In DM + Ad.SERCA2a, the oxygen cost decreased to control levels, but in DM + Ad.betaGal/DM + saline it remained high. In DM failing hearts, the high oxygen cost indicates energy wasting, which contributes to the contractile dysfunction observed in diabetic cardiomyopathy. SERCA2a gene transfer transforms this inefficient energy utilization into a more efficient state and restores systolic and diastolic function to normal.
Unusual Case of Twins
Authors: J. H. Young, F. E. Cull
Journal: BMJ (1948)

a patient aged 12 on whom he operated for increasing ob- struction with vomiting, and in whom the duodenum was two-thirds closed.In Case 2 the obstruction was of the extrinsic variety and showed the main characteristic features-i.e., bile-stained vomiting coming on soon after birth, loss of weight, and dehydration.At operation the colon was on the left side of the abdomen with the caecum in the region of the spleen, while the small gut was on the right ,side.The main interest, however, lies in the fact that the child survived the operation of gastro-jejunostomy.Forshall tabulates in her paper the previously recorded survivals after an anastomosis and reports two further cases, making in all a total of 32.Case 2 adds another to the small list. SummaryTwo cases of duodenal obstruction in the newborn are described, one of which survived gastro-jejunostomy.The syndrome of congenital occlusion of the duodenum is clear-cut, and though rare it should be recognized when it occurs and should be diagnosed early.This is important, as the condi- tion is amenable to surgical intervention, and, contrary to general belief, the very young infant stands up extremely well to the required major surgery.
Prevalence of and Risk Factors for Nonalcoholic Fatty Liver Disease: The Dionysos Nutrition and Liver Study * #
Authors: Giorgio Bedogni, Lucia Miglioli, Flora Masutti, Claudio Tiribelli, Giulio Marchesini, Stefano Bellentani
Journal: Hepatology (2005)

Abstract The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population. We therefore performed a cross-sectional study in the town of Campogalliano (Modena, Italy), within the context of the Dionysos Project. Of 5,780 eligible persons aged 18 to 75 years, 3,345 (58%) agreed to participate in the study. Subjects with suspected liver disease (SLD), defined on the basis of elevated serum alanine aminotransferase (ALT) and γ-glutamyl-transferase (GGT) activity, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)-RNA positivity, were matched with randomly selected subjects of the same age and sex without SLD. A total of 311 subjects with and 287 without SLD underwent a detailed clinical, laboratory, and anthropometrical evaluation. Fatty liver was diagnosed by ultrasonography, and alcohol intake was assessed by using a 7-day diary. Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease (NAFLD) and for alcoholic fatty liver (AFLD) versus NAFLD. The prevalence of NAFLD was similar in subjects with and without SLD (25 vs. 20%, P = .203). At multivariable analysis, normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and systolic hypertension; AFLD was more likely than NAFLD in older subjects, males, and in the presence of elevated GGT and hypertriglyceridemia, and less likely in the presence of obesity and hyperglycemia. In conclusion, NAFLD is highly prevalent in the general population, is not associated with SLD, but is associated with many features of the metabolic syndrome. (Hepatology 2005.)
In vitro, in vivo and microscopic analysis of tumor immunotherapy using combination of two antibodies against the same ErbB2 target
Authors: Gabor Toth, Arpad Szoor, Laszlo Simon, Janos Szollosi, Gyorgy Vereb
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Trastuzumab (Herceptin®), a humanized anti-ErbB2 antibody is a specific targeted therapy against ErbB2 positive tumors, with a history of both success and a high rate of therapy resistance. Another humanized antibody, pertuzumab (Perjeta®) inhibits ErbB2 heterodimerization.
Signature current of SO2-induced bronchitis in rabbit.
Authors: N Iwase, T Sasaki, S Shimura, T Fushimi, H Okayama, H Hoshi, T Irokawa, K Sasamori, K Takahashi, K Shirato
Journal: Journal of Clinical Investigation (1997)

To investigate abnormalities of airway epithelial ion transport underlying chronic inflammatory airway diseases, we performed electrophysiological, histological, and molecular biological experiments using rabbits exposed to SO2 as a model of bronchitis. By comparison with control, the SO2-exposed trachea exhibited decreased short circuit current (Isc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by diphenylamine 2-carboxylate or Cl--free bath solution. A significant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sustained Isc increase in SO2-exposed, but not in normal, tracheas. The Northern blot analysis showed a strong expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.
An Alphabet of Breast-feeding
Authors: C. McNeil
Journal: BMJ (1942)

In this third year of war the saving of food is an urgent duty, and the waste of food is strongly and rightly denounced.It is timely, therefore, to draw attention to the serious waste of breast milk caused by the prevalent neglect or mismanagement of breast-feeding.Breast milk is the ideal and complete food of the infant for the first six months of life and can continue to be its principal article of diet for the remainder of the first year.The gross quantity of breast milk consumed by a baby in six months is about 210 pints (on the basis of 3/4 pint daily for the first month and 14 pints daily for the next five months).Deducting the 41,459 infant deaths in Great Britain during 1941, there were 635,062 survivors, and their requirements in breast milk for the first six months were 16-million gallons.It is a reasonable estimate, and probably an under-estimate, that one-third of this quantity, 52 million gallons, of essential ideal infant food was lost through unnecessary weaning of babies.Of babies weaned early the great majority are weaned in the first month of life.In my ward at the Edinburgh Children's Hospital 62% of a consecutive series of 100 babies had been weaned by the end of the first month, and by the end of the second month the figure was 80%.It 'will be agreed that this early weaning of babies is due to the failure of mothers, nurses,
Evidence based budgeting is now necessary
Authors: D. Massel
Journal: BMJ (1999)

EDITOR—The BMJ 's occasional notes on economics will certainly enlighten physicians on important aspects of health economics. As Palmer and Torgerson mention, the application of economic analyses remains a challenge to decision makers everywhere.1 Although the efficiencies covered in the note are invaluable as starting points for the allocation of resources, it sometimes seems that the decision making is made easier by the application of two other global measures …
Pulmonary Embolism With Factor XI Deficiency
Authors: Jay B. Brodsky
Journal: JAMA (1975)

A patient with factor XI deficiency had pulmonary embolism, although his factor XI assay was less than 1% of normal and his postoperative course was complicated by prolonged bleeding. Programs designed to prevent postoperative venous thrombosis should be carried out in factor XI-deficient patients, since the deficient state offers no protection from a pulmonary embolus. All surgical patients who are to receive low-dose heparin therapy as a part of such a program should be screened by means of preoperative determination of the partial thromboplastin time, to identify previously unsuspected bleeding disorders.
The Status of Local Smoking Regulations in North Carolina Following a State Preemption Bill
Authors: E Conlisk, M Siegel, E Lengerich, W Mac Kenzie, S Malek, M Eriksen
Journal: JAMA (1995)

To determine the number and protectiveness of local smoking regulations adopted before the implementation of a preemptive statewide smoking control bill.Review of local smoking control regulations from all 100 counties and 85 municipalities with populations greater than 5000 in North Carolina.Adoption of local smoking control regulations before and during the 3-month delay in enactment of the preemptive bill. Protectiveness of regulations was based on restrictions on smoking and requirements for separate ventilation systems at private work sites: none (smoking unrestricted); minimal (smoking restricted to designated areas); partial (smoking restricted to designated areas served by separate ventilation systems); and complete (smoking prohibited). Because some regulations would be phased in gradually over the next 5 years, we evaluated the requirements that will be in effect by January 1, 2000.Between July 15 and October 15, 1993, the number of local smoking regulations in North Carolina increased from 16 to 105. By the year 2000, 59% of private employees still will not be guaranteed any protection from work site environmental tobacco smoke; 19% will have minimal protection, 22% will have partial protection, and none will have complete protection.The 3-month delay in preemption created an unnatural time frame for communities to organize, debate, and adopt smoking restrictions. Despite the adoption of 89 new regulations, no private employees will be guaranteed complete protection from work site environmental tobacco smoke by the year 2000; new regulations can no longer be adopted. HB 957 has been a setback for public health in North Carolina.