tbuckley/cabot-search huggingface dataset:
Disruption of leptin receptor expression in the pancreas directly affects β cell growth and function in mice
Authors: Tomoaki Morioka, Esra Asilmaz, Jiang Hu, John F. Dishinger, Amarnath J. Kurpad, Carol F. Elias, Hui Li, Joel K. Elmquist, Robert T. Kennedy, Rohit N. Kulkarni
Journal: Journal of Clinical Investigation (2007)

Obesity is characterized by hyperinsulinemia, hyperleptinemia, and an increase in islet volume. While the mechanisms that hasten the onset of diabetes in obese individuals are not known, it is possible that the adipose-derived hormone leptin plays a role. In addition to its central actions, leptin exerts biological effects by acting in peripheral tissues including the endocrine pancreas. To explore the impact of disrupting leptin signaling in the pancreas on β cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. The KOs exhibited improved glucose tolerance due to enhanced early-phase insulin secretion, and a greater β cell mass secondary to increased β cell size and enhanced expression and phosphorylation of p70S6K. Similar effects on p70S6K were observed in MIN6 β cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. Surprisingly, challenging the KOs with a high-fat diet led to attenuated acute insulin secretory response to glucose, poor compensatory islet growth, and glucose intolerance. Together, these data provide direct genetic evidence, from a unique mouse model lacking ObRs only in the pancreas, for a critical role for leptin signaling in islet biology and suggest that altered leptin action in islets is one factor that contributes to obesity-associated diabetes.
Arterial O2 Saturation and Maximum O2 Consumption in Moderate-Altitude Runners Exposed to Sea Level and 3,050 m
Authors: Alan Tucker
Journal: JAMA (1984)

Twelve trained runners, who were moderate-altitude (1,520 m) residents, were acutely exposed to sea level and 3,050-m altitude in a hypo-hyperbaric chamber. At 1,520 m, maximum O2 consumption (VO2 max) was 67.7 +/- 0.9 mL/kg/min, minute ventilation (V) at maximum exercise was 169.8 +/- 4.6 L/min, and arterial O2 saturation (SaO2) decreased from 93.3% +/- 0.9% at rest, to 84.5% +/- 1.6% at maximum exercise. Exposure to 3,050 m produced a lower VO2max (56.5 +/- 1.5, -16.5%), a similar V at maximum exercise (169.9 +/- 6.0), and a similar fall in SaO2 (from 89.1% +/- 0.8% to 79.5% +/- 0.8%). Exposure to sea level increased VO2max to 72.4 +/- 1.4 (+6.9%), reduced V at maximum exercise to 158.8 +/- 6.5, and induced a smaller fall in SaO2 (from 96.9% +/- 0.4% to 92.1% +/- 1.0%). These changes are comparable with those reported previously in athletes at sea level exposed to similar altitudes, suggesting that residence at 1,520 m does not improve VO2max in highly trained athletes acutely exposed to lower or higher altitudes.
Antenatal screening for intrauterine growth retardation with umbilical artery Doppler ultrasonography.
Authors: R. B. Beattie, J. C. Dornan
Journal: BMJ (1989)

To assess the usefulness of continuous wave Doppler ultrasonography as an antenatal screening tool for the detection of intrauterine growth retardation and fetal compromise 2097 singleton pregnancies were studied. Umbilical artery velocity waveforms were obtained at 28, 34, and 38 weeks of gestation, from which the pulsatility index, A/B ratio, and resistance parameter were calculated. No abnormal features or indices of neonatal outcome were adequately predicted. The most sensitive index for being delivered of a growth retarded infant (less than 5th centile birth weight for gestation) was an A/B ratio at 34 weeks (sensitivity 40%, specificity 84%). Other measures that show poor neonatal nutritional state (ponderal index, skinfold thickness, and ratio of mid-arm circumference to head circumference) were even less well predicted. Acute and chronic hypoxia as determined by Apgar score, pH in blood from the cord artery, and packed cell volume correlated poorly with umbilical artery waveform indices, and there was no obvious difference between the indices of those who subsequently required operative or instrumental delivery for fetal distress and those requiring no intervention. There were three unexplained stillbirths in the series, in each of which the fetus had shown waveform patterns that suggested increased peripheral resistance, though the technique did not appear to be useful for predicting the time of subsequent death. Screening for small for dates babies in a three stage programme was of no value regardless of the threshold or index chosen. Obstetricians should resist the temptation to introduce screening with Doppler ultrasonography until its proper role has been determined.
NHS IT is at the mercy of the civil service and "gifted amateurism"
Authors: G. S.-B. Kelly
Journal: BMJ (2011)

Greenhalgh and Bowden comment on New Zealand’s learning environment for health informatics versus our own cathedral approach.1 2 I suggest we are unlikely to change our approach until we escape from the civil service.

As a clinical adviser to the NHS National Programme for IT, I was repeatedly told that civil …
Inhibition of nocturnal acidity is important but not essential for duodenal ulcer healing.
Authors: G Bianchi Porro, F Parente, O Sangaletti
Journal: Gut (1990)

We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double-blind therapy with ranitidine 300 mg at 8 am or the same dose at 10 pm for up to eight weeks. The antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring in 18 of these patients. At four weeks ulcers had healed in 41/61 (67%) of patients taking the morning dose and in 47/63 (75%) of those receiving the nocturnal dose (95% CI for the difference -0.09 +0.25; p ns). At eight weeks, the corresponding healing rates were 82% and 85.5%, respectively (95% CI for the difference -0.11 +0.17; p ns). Both treatments were significantly superior to placebo in raising 24 h intragastric pH, although the effects of the morning dose were of shorter duration than those of the nocturnal dose. These findings suggest that suppression of nocturnal acidity is important but not essential to promote healing of duodenal ulcers; a prolonged period of acid inhibition during the day (as obtained with a single large morning dose of H2-blockers) may be equally effective.
Outcomes in the Era of Bare-Metal Stents vs the Era of Drug-Eluting Stents
Authors: Jeremy A. Rassen
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical Crossroads: A 36-Year-Old Woman Recuperating From Stroke
Authors: Lombardo Palma
Journal: JAMA (1997)

<h3>To the Editor.</h3> —A recent Clinical Crossroads<sup>1</sup>began with the case of Mrs X's recovery from a severe ischemic stroke, probably due to thromboembolic phenomena generated by severe mitral stenosis. Although Dr Alexander, the discussant, presented the case differently, after detailed reading I am recounting the case as follows. The patient was treated with recombinant tissue-type plasminogen activator (rt-PA) within the Food and Drug Administration's (FDA's) approved time window. I assume her coagulation test results were normal before administration of thrombolytic therapy, although those findings were not given. The patient's condition deteriorated over the next 2 days; she became drowsy and lethargic. Despite this clinical observation, I am surprised that no standardized stroke scales were used to document this change objectively. A time plot of the values of a neurologic deficit stroke scale would have made this neurologic decline evident. Additionally, this would have suggested the need to repeat the
Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and alpha-adrenergic receptors.
Authors: P Apprill, J M Schmitz, W B Campbell, G Tilton, J Ashton, S Raheja, L M Buja, J T Willerson
Journal: Circulation (1985)

The phospholipid platelet-activating factor (PAF) stimulates platelet aggregation and coronary vasoconstriction. In this study we determined whether PAF alters coronary flow patterns in vivo in a canine preparation with concentric coronary artery stenosis. This preparation is characterized by cyclic flow variations in coronary blood flow associated with transient platelet aggregation at the site of the coronary constriction. Thirty-nine male mongrel dogs were used in three protocols. In protocol 1, PAF (10(-9) or 10(-8) mol/min) was infused into the coronary artery proximal to the stenosis to determine (1) whether PAF induces cyclic flow variations and (2) whether PAF has an effect on systemic hemodynamics. Cyclic flow variations were induced in three of six dogs; in these animals, mean arterial pressure decreased by 5.5% and 42.1% 10 min after infusion of the lower and higher dose of PAF. In protocol 2, cyclic flow variations were abolished with either the thromboxane synthetase inhibitor UK38485 (mean dose 2.2 mg/kg iv), the serotonin antagonist ketanserin (0.5 mg/kg iv), or the alpha 2-adrenergic antagonist yohimbine (2 mg/kg iv). Subsequent administration of PAF restored the frequency of cyclic flow variations to the preantagonist levels. Thromboxane (Tx) B2 and 6-keto-PGF1 alpha, the stable metabolites of TxA2 and prostacyclin, respectively, were measured in blood obtained distal to the coronary stenosis. TxB2 levels increased substantially during cyclic flow variations and were returned to control values with the thromboxane synthetase inhibitor UK38485. Infusion of PAF subsequently restored cyclic flow variations without altering coronary arterial coronary arterial TxB2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Failure to Compensate Decreased Dietary Sodium With Increased Table Salt Usage
Authors: Gary K. Beauchamp
Journal: JAMA (1987)

This study tested the extent to which individuals placed on a lowered sodium diet would compensate for the reduced dietary sodium by adding table salt to their food. Eleven students, unaware that their use of saltshakers was being studied, consumed all their meals and snacks in a clinical research center for 13 weeks. During the first three weeks and the last week (week 14), the diet contained approximately 135 mmol/d (135 mEq/24 h) of sodium, which was reduced to approximately 70 mmol/d (70 mEq/24 h) during weeks 4 through 13. A preweighed saltshaker was available for use throughout the entire 14-week period. Evaluations of salt taste preference and intensity scaling were conducted at regular intervals. Subjects compensated only slightly for the reduction of dietary sodium, making up less than 20% of the decrement with increased saltshaker usage. No changes in taste function were found. A substantial reduction in dietary sodium is possible if lowered-sodium foods are consumed in conjunction with ad libitum table salt. (<i>JAMA</i>1987;258:3275-3278)
Ontogenic development and tissue distribution of V gamma 1-expressing gamma/delta T lymphocytes in normal mice.
Authors: P Pereira, D Gerber, S Y Huang, S Tonegawa
Journal: The Journal of Experimental Medicine (1995)

A hamster monoclonal antibody (mAb) recognizing an epitope in the V gamma 1-J gamma 4-C gamma 4 chain of the gamma/delta T cell receptor has been generated. Using this mAb, we have quantitated the occurrence of V gamma 1-bearing gamma/delta T cells in the developing thymus and in the lymphoid organs and several epithelia of adult mice. The V gamma 1-expressing cells constitute a minor gamma/delta T cell subpopulation during fetal and early postnatal life, but they constitute a major population of gamma/delta T cells in the thymus and in the peripheral lymphoid organs in adult mice. In addition, we found that V gamma 1-bearing cells comprise a large proportion (15-60%) of the gamma/delta T cells present in the intestinal epithelium (i-IEL) in all strains of mice tested. V gamma 1+ i-IEL are present in athymic (nude) mice and in antigen-free mice, demonstrating that they can develop extrathymically and that their presence in the intestinal epithelium is independent of the antigenic load of the gut. Our results show that V gamma 1-bearing lymphocytes account for the largest population of gamma/delta T cells in the mouse. This population includes a thymus-dependent component that homes to the secondary lymphoid organs and a thymus-independent component that constitutes a major fraction of the gamma/delta i-IELs.
Internal and external morality of medicine: lessons from New Zealand
Authors: C. Paul
Journal: BMJ (2000)

It has been claimed that the Bristol case will kill internal self regulation.1 The New Zealand experience should serve as a warning against believing that internal self regulation by the medical profession is useless and should be discarded. After the report of the New Zealand cervical cancer inquiry 11 years ago,2 which has similarities with the Bristol case, many new rules were made, some of which have the status of legal regulations, governing both research and medical practice. Yet these apparent improvements in ethical standards represent an unbalanced concentration on an external morality for medicine. Over the same time internal morality, though it had a key role in limiting the harm done to patients in the cervical cancer study, has been thoroughly neglected.

Henk ten Have has described internal morality as those values, norms, and rules that are intrinsic to the practice of medicine.3 Internal morality arises from within a community of practitioners—doctors, nurses, teachers—and it is based on how one should behave in one's daily work. These are shared values that are learnt from one another and may or may not be written down. External morality is the view from outside, reflecting the ethos of the wider society. The recent discipline of bioethics has grown up largely outside medicine and has developed principles of its own. Rules drawn from principles in bioethics and from other ethical doctrines in society are often codified into laws.

The best known written code for practitioners, drawn up by insiders, is the Hippocratic oath.4 A central statement is: “I will use my power to help the sick to the best of my ability and judgment; I will abstain from harming or wronging any person by it.” The code is written in the first person—a moral agent is envisaged. The most …
Urinary ethyl glucuronide as a novel screening tool in patients pre- and post-liver transplantation improves detection of alcohol consumption
Authors: Katharina Staufer, Hilke Andresen, Eik Vettorazzi, Niels Tobias, Bjoern Nashan, Martina Sterneck
Journal: Hepatology (2011)

Optimal selection of liver transplant candidates and early detection of alcohol relapse after orthotopic liver transplantation (OLT) is necessary to improve long-term outcomes. In this study, urinary ethyl glucuronide (uEtG) was prospectively evaluated as a novel screening tool for alcohol detection in the transplant setting. Overall, 141 liver transplant candidates and recipients, visiting the outpatient clinic for a total of 308 times, were included. At each visit, the alcohol markers, uEtG, ethanol, methanol, and carbohydrate-deficient transferrin (CDT), as well as the state markers, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV), were determined, then compared to patients' self-reports on alcohol intake. Urinary EtG significantly increased the detection rate of alcohol consumption, compared to the other alcohol markers (P < 0.001). In 93% of patients and at 92.5% of visits with positive alcohol markers, alcohol intake was detected by uEtG and/or CDT. Sensitivity and specificity of uEtG were 89.3% and 98.9% and of CDT were 25% and 98.6%, respectively. Urinary EtG was the best independent predictor of alcohol consumption in univariate and multivariate analysis (positive predictive value: 89.3%; negative predictive value: 98.9%; odds ratio: 761.1; P < 0.001). It showed a superior prediction rate, when compared to established alcohol and state markers, as well as to the combination of CDT with MCV and GGT, assessed by net reclassification improvement (NRI) (NRI: 1.01, P < 0.001; NRI: 1.755, P < 0.001).uEtG is a sensitive, specific, and reliable marker for the detection of recent alcohol intake pre- and post-OLT. In combination with CDT, uEtG should be considered as a tool for routine alcohol screening within the transplant setting.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Stewart Sell
Journal: The Journal of Experimental Medicine (1967)

The addition of sheep antisera to rabbit IgG or to rabbit IgG subunits (L chain, H chain, Fab piece, Fc piece) to in vitro cultures of rabbit peripheral lymphocytes may induce up to 80–90% of the small lymphocytes to transform into immature "blast" cells. As many as 1 x 107 molecules of antibody may be required to stimulate each cell. It is concluded that each peripheral lymphocyte carries the antigenic specificities of the entire IgG molecule and thus could carry, and may produce specific antibody molecules. Such a conclusion supports the theory that the small lymphocyte may be the site of specific recognition of antigens in the primary response.
Hospital set up over the week explains difference in mortality for elective surgery
Authors: A. M. Verma
Journal: BMJ (2013)

After the media tsunami to Aylin and colleagues’ analysis, I read the paper carefully to discover why the 30 day mortality for elective surgery on Monday and at the weekend is significantly different.1

The media suggest that at weekends work-shy consultants are absent, leaving junior doctors to run amok and kill patients. I have noticed that weekend elective lists are mainly waiting …
Endoscopic Percutaneous Gastrostomy Using a Modified Instrument for Puncture of the Abdominal Wall and the Stomach
Authors: D. Reichenbacher, K. D. Rückauer, R. Salm, H. J. Sontheimer
Journal: Endoscopy (1989)

A new instrument for the puncture of the abdominal wall and stomach while performing endoscopic percutaneous gastrostomy is described. It has several advantages as compared with the instruments used so far, one of which is that it makes the method safer and easier.
Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells.
Authors: S B Rodan, K L Insogna, A M Vignery, A F Stewart, A E Broadus, S M D'Souza, D R Bertolini, G R Mundy, G A Rodan
Journal: Journal of Clinical Investigation (1983)

The culture media of three cell lines, a human prostate carcinoma (PC3), a rat Leydig cell tumor (Rice-500), and a rat carcinosarcoma (WRC-256), that were derived from tumors associated with humoral hypercalcemia of malignancy (HHM), were examined for stimulation of adenylate cyclase in ROS 17/2.8 osteoblastic cells and for bone resorptive activity in culture. Cells from a nonhypercalcemic variant of the WRC256 tumor served as control. Extracts from three solid human tumors, a lung adenocarcinoma from a patient with HHM and two adenocarcinoma from normocalcemic patients (lung and colon), were also examined for adenylate cyclase stimulation. We found excellent correlation between stimulation of cyclic AMP accumulation in ROS 17/2.8 cells and bone resorbing activity in culture, or production of HHM in vivo. Stimulation of adenylate cyclase by HHM factors was inhibited by the parathyroid hormone competitive inhibitor, [8norleucyl, 18norleucyl, 34tyrosinyl] bovine parathyroid hormone (3-34) amide.
Complacency in diagnosis of cervical cancer.
Authors: M J Campion, A Singer, H S Mitchell
Journal: BMJ (1987)

Bronchoalveolar lavage -Cytology--Microbiology -Virology (cytomegalovirus, cytopathic effect in cell culture.In some centres detection of a and ,B proteins (early proteins produced in cytomegalovirus replication 4-6 hours after cell infection)Transbronchial biopsy -Histology -Microbiology (fungi, alcohol and acid fast bacilli, bacteria) -VirologyGallium scanning has been used extensively in the United States in patients with AIDS but less so in the United Kingdom.Gallium scans are frequently abnormal in Pneumocystis carinii pneumonia but also in the other respiratory manifestations ofAIDS and are non-specific.We do not use this technique in our patients. Open lung biopsyThis procedure may often be the only method to diagnose parenchymal Kaposi's sarcoma or lymphoid interstitial pneumonia.-Mechanical ventilation Whatever the diagnosis or method used to achieve it, some patients will progress to respiratory failure, often rapidly, and the question ofventilation will arise.Experience with mechanical ventilation has shown universally poor results.In one large series no patient who had survived ventilation was alive at one year.Patients with Pneumocystis caninii pneumonia who do not respond to therapy and go into respiratory failure rarely improve through mechanical ventilation.There cannot be a uniform policy but mechanical ventilation seems appropriate as an exception rather than the rule.