tbuckley/cabot-search huggingface dataset:
Demonstration of a lack of change in serum 1 alpha,25-dihydroxyvitamin D in response to parathyroid extract in pseudohypoparathyroidism.
Authors: P W Lambert, B W Hollis, N H Bell, S Epstein
Journal: Journal of Clinical Investigation (1980)

Studies were carried out to compare the effects of parathyroid extract (PTE) on serum and urinary calcium (Ca) and phosphorus (P), serum 25-hydroxyvitamin D (25-OHD), serum 24,25-dihydroxyvitamin D (24,25(OH)2D), serum 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), and urinary cyclic AMP in two normal subjects, two patients with hypoparathyroidism (HP) and six patients with pseudohypoparathyroidism (PHP), some of whom were on suboptimal treatment with vitamin D. Two of the patients with PHP were studied while on long-term treatment with 1 alpha,25-(OH)2D3. Before PTE, serum 1 alpha, 25(OH)2D was at the lower limit of normal in one patient and was abnormally low in the other five patients. None of these individuals was on treatment with 1 alpha,25(OH)2D3. Serum 25-OHD and 24,25(OH)2D were either increased or at the upper limit of normal in the patients given vitamin D and were normal in the other patients. PTE lowered the serum P and increased the serum 1 alpha,25(OH)2D, serum and urinary Ca, urinary P, and urinary cyclic AMP in the normal subjects and patients with HP. In individual studies, changes in serum 1 alpha,25(OH)2D and serum Ca occurred in parallel before, during, and after PTE. In contrast, PTE had very little effect in the patients with PHP. Whereas there were highly significant positive correlations between serum 1 alpha,25(OH)2D in each of the normal subjects and patients with HP, there were significant correlations in only one of the patients with PHP. An increase in serum Ca in response to PTE was observed in one of the two patients with PHP who were on long-term treatment with 1 alpha,25(OH)2D3. In these individuals, PTE produced only slight increases in serum 1 alpha,25(OH)2D. Serum 25-OHD and 24,25(OH)2D were not changed by PTE in any of the subjects or patients. The results provide evidence that hypocalcemia in HP and PHP arises in part from low circulating 1 alpha,25-(OH)2D, and indicate that the lack of change in serum 1 alpha,25(OH)2D with PTE in patients with PHP is related to impaired renal adenylate cyclase and phosphaturic responses. These and previous results support the idea that diminished renal production of 1 alpha,25(OH)2D, because of a defect in the parathyroid hormone-responsive adenylate cyclase system, may be a contributing factor in the pathogenesis of the abnormal calcium metabolism in PHP.
Inflammatory response is modulated by mitochondrial dysfunction in cultured normal human chondrocytes
Authors: C Vaamonde-Garcia, N Valcarcel-Ares, R Riveiro-Naveira, B Lema, F J Blanco, M J Lopez-Armada
Journal: Annals of the Rheumatic Diseases (2010)

PurposeThe molecular infl ammation hypothesis of ageing implies that the molecular activation of proinfl ammatory genes by altered redox-sensitive cellular signal pathway might serve as a bridge between normal ageing and age-related diseases such as osteoarthritis (OA).We studied the effect that dysfunction of the mitochondrial respiratory chain (MRC), the main cellular source of reactive oxygen species (ROS), could induce on the infl ammatory response in cultured normal human chondrocytes, specifi cally in interleukin 8 (IL8) and cyclooxygenase 2 (COX-2) expression.Method Antimycin A (AA) (10 µg/ml) and oligomycin (Oli) (10 µg/ml) were employed as inhibitors of complex III and V of MRC, respectively.IL1β or tumour necrosis factor α (TNFα) were used as inductors of the infl ammatory response.Protein and mRNA IL8 and COX-2 expression were analysed by cytometry and real-time PCR and prostaglandin E2 (PGE2) levels were assayed by ELISA.To identify underlying mechanisms responsible for the infl ammatory response, a chemical and a natural ROS scavenger, N-acetyl-L-cysteine (NAC) (40 mM) and resveratrol (RESV) (250 µM) respectively, were employed.Finally, the effect of nuclear factor κB (NF-κB) was studied by the inhibitor BAY-117085 (5 µM). ResultsWe fi rst tested if mitochondrial dysfunction induced by AA or Oli could modulate the response induced by IL1 (5, 1.5 and 0.5 ng/ml) on IL8 expression.The results showed that the pretreatment of chondrocytes with AA or Oli for 1 h increased signifi cantly the expression of IL8 induced by IL1, both mRNA and protein level (214.06±35.22%AA+IL1 or 292.06±49.02%Oli+IL1 vs 100% IL1 1.5 ng/ml, p<0.01).Similar effects were observed with 10 ng/ml TNF.In addition, the intensifi cation of the infl ammatory effects of cytokines by mitochondrial dysfunction was counteracted by the addiction of a chemical and a natural ROS scavenger (10.75±2.97%NAC+AA+IL1 or 18.10±5.04%RESV+AA+IL1 vs 100% AA+IL1, p<0.01).When the role of NF-κB was on July 19,
Produce a service specification.
Authors: D Webster
Journal: BMJ (1991)

likely status as an orphan in the future.It might be interesting to consider whether the child could bring an action against the gynaecologist for "wrongful life."Consideration should also be given to any risk, however slight, of HIV transmission to health care staff involved in the care of such patients." The obverse viewpoint is that aware, consenting patients have the right to determine the course of their own child bearing, in much the same fashion as HIV infected women can elect to continue with their pregnancy rather than have a termination.It is also possible that after being refused treatment for infertility the couple could present themselves elsewhere and fail to disclose their HIV state.For the asymptomatic couple it is unlikely that their HIV state would be detected.After careful consideration we did not feel justified in managing their infertility.We informed the couple of our decision not to undertake active management and they accepted this.The couple were also told that it was their right to seek a second opinion.We do, however, feel that patients deserve sympathetic counselling and that an explanation of their infertility in selected cases may assist this.We explained to the couple that in the future, developments may occur which will reduce the vertical transmission rate and increase life expectancy, necessitating a change in this view.We were careful to make it clear that this was unlikely, particularly in the short term.
Thin layer chromatography and counter-current analysis in porphyrias
Authors: J.PINOL AGUADE, C. HERRERO, J. ALMEIDA, S.G. SMITH, R.V. BELCHER
Journal: British Journal of Dermatology (1975)

The porphyrin metabolism of 100 patients with porphyria and 351 of their relatives has been studied. Thin layer chromatography of methyl esters of the urinary porphyrin was undertaken in sixty-six patients with different types of porphyria, and forty-five relatives, seventeen patients with hepatic cirrhosis, three patients with lead poisoning and twenty normal control subjects. This investigation was also made on the stools of thirty-six patients with porphyria, and then of their relatives. Countercurrent analysis of the bile of nine selected patients with porphyria was also undertaken. The results provide some evidence that symptomatic hepatic porphyria may be familial. Thin layer chromatography was decisive in the characterization of a new type of porphyria described recently by the authors (hepato-erythrocytic porphyria). The counter-current examination of the bile showed the absence of the 'S 411' porphyrin in all the nine cases investigated.
Influenza Vaccine Efficacy
Authors: Timothy F. Nolan
Journal: JAMA (1981)

At times, it would appear that the only constant feature of influenza is inconstancy. The antigenic structure of the influenza A virus undergoes frequent alterations. In some years, the alterations are relatively small (antigenic drift), while in others, they are drastic (antigenic shift). Antigenic shift or significant antigenic drift decreases the efficacy of a particular influenza vaccine, requiring frequent updating of the vaccine formulation. Published estimates of vaccine efficacy have varied widely since the vaccine's introduction in the early 1940s. In some studies, such as that by Foy et al in this issue ofThe Journal(p 1736), the incidence of respiratory illness did not differ noticeably between vaccinated and unvaccinated groups, while in other studies, the vaccine efficacy (ie, the percent of decrease in illness rates in vaccinees) has been as high as 90%.<sup>1</sup> The practice of expressing vaccine efficacy as a single number belies the fact that
The neuroendocrine-immune interface gone awry in aldosteronism
Authors: K WEBER
Journal: Cardiovascular Research (2004)

Congestive heart failure (CHF), a clinical syndrome with characteristic signs and symptoms, is a salt-avid state whose origins are rooted in neurohormonal activation, including the circulating renin-angiotensin-aldosterone system (RAAS).A systemic illness accompanies CHF and contributes to a progressive downhill clinical course and poor prognosis.Features include: (a) oxi/nitrosative stress in such diverse tissues as skin, skeletal muscle, heart, lymphocytes and monocytes; (b) a proinflammatory phenotype involving multiple tissues and blood and expressed as elevated levels of chemokines and such cytokines as IL-6 and TNF-a; and (c) a catabolic state with loss of lean tissue, fat and bone that eventuates in a wasting syndrome termed cardiac cachexia.The pathophysiology of CHF includes a neuroendocrineimmune interface gone awry.This brief commentary, prepared in response to the study from the Leenen laboratory in Ottawa [1], focuses on this interface in aldosteronism.Apologies are extended for the limited discussion and literature citations dictated by space constraints.
The Problem of the Three Isaac Rands
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1959)

SOME years ago, while the publications issued during the Ether Controversy in 1846 were being investigated, the name of Edward Warren frequently recurred. There were, in fact, three Edward Warrens, all associated with the first public demonstration of ether anesthesia, and since much confusion had arisen in the literature regarding these three persons a note was made about them.1 From this minor bit of historical research came a large number of letters of appreciation. A somewhat similar situation arises in relation to the three Isaac Rands, each of whom practiced medicine in or near Boston at the close of the . . .
Pharmacodynamic Effects of a New Antihypertensive Drug, Catapres (ST-155)
Authors: GADDO ONESTI, ALLAN B. SCHWARTZ, KWAN E. KIM, CHARLES SWARTZ, ALBERT N. BREST
Journal: Circulation (1969)

Catapres is a new imidazoline compound with potent antihypertensive properties. Significant reduction in blood pressure occurs between 1 and 4 hours after oral administration, with the peak effect occurring at 2 to 4 hours and the antihypertensive effect extending for 6 to 10 hours. Blood pressure is reduced in both the supine and erect positions, although the orthostatic response is the more prominent. Cardiac output is reduced moderately in both the supine and erect positions. Peripheral vascular resistance is also reduced, particularly in the erect posture. Accordingly, the cardiac hemodynamic findings suggest that the antihypertensive effect of Catapres is related to the combination of reduction in cardiac output plus decrease in peripheral resistance. Renal blood flow and glomerular filtration rate are preserved in both the supine and erect positions following Catapres administration. Contrasting with the preservation of renal blood flow and glomerular filtration rate, however, is the marked reduction in sodium chloride excretion which follows acute administration of the drug. The clinical utility of the drug was demonstrated in the chronic outpatient study. Although Catapres administered alone exerted only modest antihypertensive effects, a markedly enhanced antihypertensive response was achieved when the drug was combined with a potent oral diuretic, with 80% of patients so treated achieving significant blood pressure reduction in both the supine and erect positions.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Werner Straus, Jean Oliver
Journal: The Journal of Experimental Medicine (1955)

Immunological analysis with a specific antiserum showed an increasing concentration of egg white proteins in the cortex of the kidney of the rat up to 18 hours after their intraperitoneal injection, and a fall in the following 40 hours. Homogenates of the cortical tissue prepared at 18 hours, the period of maximum droplet development, showed a large amount of the egg white proteins in the supernatant, considerable amounts in the fraction which contained the mitochondria, but the highest concentration, 6 times that of any other cell fraction, in the highly purified preparation of droplets. The relation of these findings to the morphological and histochemical evidence concerning the constitution of the droplets is discussed and the conclusion drawn that absorbed egg white proteins and mitochondrial substances are important elements in their formation.
Mutation of the Gene for <i>I</i> sK Associated With Both Jervell and Lange-Nielsen and Romano-Ward Forms of Long-QT Syndrome
Authors: Priya Duggal, Mark R. Vesely, Duangrurdee Wattanasirichaigoon, Juan Villafane, Vineet Kaushik, Alan H. Beggs
Journal: Circulation (1998)

Background —Long-QT syndrome (LQTS) is a disorder of ventricular repolarization characterized by a prolonged QT interval, syncope, seizures, and sudden death. Recently, three forms of LQTS have been shown to result from mutations in potassium or sodium ion channel genes: KVLQT1 for LQT1, HERG for LQT2, and SCN5A for LQT3. I sK, an apparent potassium channel subunit encoded by KCNE1 on chromosome 21, regulates both KVLQT1 and HERG. This relationship makes KCNE1 a likely candidate gene, because mutations of these genes are known to cause both the autosomal dominant Romano-Ward and recessive Jervell and Lange-Nielsen (JLN) forms of LQTS. Methods and Results —We screened 84 unrelated patients with Romano-Ward and 4 with JLN for possible mutations in KCNE1 . We identified one homozygous mutation in a JLN patient that results in the nonconservative substitution of Asn for Asp at amino acid 76. The patient is congenitally deaf-mute, with recurrent syncopal events and a greatly prolonged QT c interval. The proband’s mother and half-sister are both heterozygous for this mutation. Remarkably, both these family members have prolonged QT c intervals and would have been classified as Romano-Ward patients if not for the proband’s diagnosis of JLN. This mutation was not identified in more than 100 control individuals. Conclusions —These data provide strong evidence that KCNE1 mutations represent a fifth LQTS locus (LQT5). Further functional analysis, as well as the identification of more LQTS patients with KCNE1 mutations, will be important to confirm the role of I sK in LQTS.
Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis
Authors: Toshiya Kamiyama, Hideki Yokoo, Jun-Ichi Furukawa, Masaki Kurogochi, Tomoaki Togashi, Nobuaki Miura, Kazuaki Nakanishi, Hirofumi Kamachi, Tatsuhiko Kakisaka, Yosuke Tsuruga, Masato Fujiyoshi, Akinobu Taketomi, Shin-Ichiro Nishimura, Satoru Todo
Journal: Hepatology (2013)

The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 μL serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion.Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;).
Diachronic evidence for a dual-mechanism approach to inflection
Authors: David Fertig
Journal: Behavioral and Brain Sciences (1999)

The received view in historical linguistics is that there is always an inverse relation between token frequency and likelihood of analogical change. I have found evidence, however, of a sharp difference in frequency effects between regularization and nonregularizing analogical change. I argue that this difference can easily be accounted for by dual-mechanism models of inflection but is very problematic for pure associative-memory models.
Christmas Message, 1975
Authors: Hugh H. Hussey
Journal: JAMA (1975)

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Trans-Atlantic learning
Authors: Douglas Kamerow
Journal: BMJ (2005)

Since we are the US version of what used to be called the British Medical Journal , it is not surprising that we are interested—not to say obsessed—with what goes on in the United Kingdom. A few months ago, some of our London colleagues worked with BMJ USA Associate Editor Bob Phillips to commission a series of articles from experts on both sides of the Atlantic asking what the two countries could learn from each other's health care systems. The results are being published both …
COMBINED ATRIOVENTRICULAR LONGITUDINAL STRAIN RATE DURING ISOVOLUMIC CONTRACTION PREDICTS PULMONARY CAPILLARY WEDGE PRESSURE IN PATIENTS WITH SYSTOLIC DYSFUNCTION
Authors: Alaa M. Omar, Mohamed A. Abdel-Rahman, Mostafa Helmy, Hazem Khorshid, Hala Raslan, Osama Rifaie
Journal: Journal of the American College of Cardiology (2014)
Rehabilitation of amputees.
Authors: J. A. Lindsay
Journal: BMJ (1992)

drugs should aim at an even larger number of patients and continue longer.The planning of this study started in 1985 after our first results2 were available; at this time there were no human data suggesting a renal protective effect of angiotensin converting enzyme inhibitors.Peter T Sawicki and Michael Berger seem to recommend a comparison of enalapril and metoprolol treatments during the follow up period from six months onwards, and that only patients with follow up times of one year or more be included.A total of 18 patients treated with enalapril and 13 treated with metoprolol are evaluable in this respect.During this period the mean (SD) rate of change in glomerular filtration rate was 0-8 (4 7) ml/min/year in the enalapril treated and -3 3 (4 2) ml/min/year in the metoprolol treated patients (p= 0 016).The mean arterial blood pressures (mean of supine and standing pressures) were 102 (5) mm Hg and 103 (4) mm Hg, respectively.Multiple regression analysis shows that enalapril or metoprolol treatment was correlated to the rate of fall in glomerular filtration rate (p=002) but mean arterial blood pressure was not (p=0 8).If supine or standing mean arterial blood pressure is used, neither result is significant (p=026 and 0-4, respectively).Thus, in our enalapril treated patients there was no fall in glomerular filtration rate after the first six months.Blood pressure was less important for the prognosis of renal function than type of antihypertensive treatment in these patients with well controlled blood pressure.
REDUCTION OF MYOCARDIAL INFARCTION WITH VORAPAXAR: RESULTS FROM THE TRA&amp;middot;CER TRIAL
Authors: Sergio Leonardi, Pierluigi Tricoci, Harvey White, Paul Armstrong, Zhen Huang, Lars Wallentin, Philip Aylward, David Moliterno, Frans Van de Werf, Edmond Chen, Luis Providencia, Jan Erik Nordrehaug, Claes Held, John Strony, Tyrus Rorick, Robert Harrington, Kenneth Mahaffey
Journal: Journal of the American College of Cardiology (2012)
Non-Ulcer Dyspepsia: Potential Causes and Pathophysiology
Authors: NICHOLAS J. TALLEY
Journal: Annals of Internal Medicine (1988)

Dyspepsia, defined as chronic or recurrent upper abdominal pain or nausea, is a common occurrence. Dyspepsia without an ulcer (non-ulcer dyspepsia) is diagnosed in patients at least twice as often as peptic ulceration. Diseases that may present with similar symptoms include gastroesophageal reflux, biliary tract disease, chronic pancreatitis, and irritable bowel syndrome. A careful history and physical examination, supplemented by selected tests, usually lead to a correct diagnosis. The pathogenesis of non-ulcer dyspepsia remains unknown. Gastric acid secretion, duodenogastric reflux, psychological factors, environmental exposures, and heredity probably do not play a major role. Some patients may have motility disturbances, but whether these disturbances cause dyspepsia is unknown. Campylobacter pylori infection and associated gastritis are common in non-ulcer dyspepsia, but their etiologic role is controversial, as is the importance of chronic duodenitis. By recognizing the heterogeneity of patients who present with non-ulcer dyspepsia, more rational management may be possible. Although an empiric trial of antacids or H2 blockers has been recommended to treat dyspepsia, most controlled trials show that although these substances reduce severity of symptoms, they are no more effective than placebos in non-ulcer dyspepsia.
Inaccuracies in obituaries should not be ignored
Authors: E. Wilson
Journal: BMJ (1997)

Editor—I must correct some of the factual errors in the obituary on Gladys “Margaret” Pappworth (nee Curtis).1 I knew Margaret Curtis well in the 1960s and early '70s, and I trained her in the Family Planning Association's clinic in Attercliffe, in Sheffield. Our clinic was by then both efficient and professional; it was one of the first to start prescribing the pill, several years before Dr Curtis's arrival there, and was recognised nationally …