tbuckley/cabot-search huggingface dataset:
A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response
Authors: Nico Scheer, Jillian Ross, Anja Rode, Branko Zevnik, Sandra Niehaves, Nicole Faust, C. Roland Wolf
Journal: Journal of Clinical Investigation (2008)

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals. Both receptors regulate the expression of genes involved in the biotransformation of chemicals in a ligand-dependent manner. As the ligand specificity of PXR and CAR have diverged between species, the prediction of in vivo PXR and CAR interactions with a drug are difficult to extrapolate from animals to humans. We report the development of what we believe are novel PXR- and CAR-humanized mice, generated using a knockin strategy, and Pxr- and Car-KO mice as well as a panel of mice including all possible combinations of these genetic alterations. The expression of human CAR and PXR was in the predicted tissues at physiological levels, and splice variants of both human receptors were expressed. The panel of mice will allow the dissection of the crosstalk between PXR and CAR in the response to different drugs. To demonstrate the utility of this panel of mice, we used the mice to show that the in vivo induction of Cyp3a11 and Cyp2b10 by phenobarbital was only mediated by CAR, although this compound is described as a PXR and CAR activator in vitro. This panel of mouse models is a useful tool to evaluate the roles of CAR and PXR in drug bioavailability, toxicity, and efficacy in humans.
Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.
Authors: A J MacGilchrist, G G Birnie, A Cook, G Scobie, T Murray, G Watkinson, M J Brodie
Journal: Gut (1986)

Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.
Theoretical and Practical Problems of Medicine and Biology in Experiments on Monkeys
Authors: George Halperin
Journal: JAMA (1961)

The Russians have a medicobiological station at Sukhumi, now referred to as the Institute for Experimental Pathology and Therapeutics. The Institute has excellent facilities for experimentation on monkeys. This small volume is devoted exclusively to the study of physiological and pathological problems as seen in monkeys. Part 1 deals with the physiology and pathology of higher nervous activity in monkeys; part 2 with pathological morphology and physiology; and part 3 with the pathology of infectious diseases in monkeys. The data obtained are valuable because of close physiological and pathological relationship of monkeys to man.
A 79 year old man with a lesion on his cheek
Authors: A. W. N. Reid, O. P. Shelley
Journal: BMJ (2012)

A 79 year old man was referred to the plastic surgery outpatients department because he was worried about a 7 mm diameter lesion on his right cheek (fig 1⇓).



He first noted this lesion a year earlier, and it had slowly grown in size since. It crusts over occasionally, but it does not bleed. He had spent most of his adult life in Africa. His medical history includes hypertension, for which he takes atenolol and ramipril. He has no drug allergies and is a non-smoker.



### 1 What is the most likely diagnosis?

#### Short answer

Basal cell carcinoma.

#### Long answer

Basal cell carcinomas are slow growing malignant tumours that arise from the stratum germinativum, the deepest layer of the epidermis.1

Dermatoscopy (examination of skin lesions with a handheld dermatoscope) typically shows a cystic pearly appearance with raised areas of telangiectasia. However, several histological subtypes exist, and their morphology and …
THE SOCIAL MALADJUSTMENT UNIT: A COMMUNITY WIDE APPROACH TO THE PROBLEM OF DELINQUENT BEHAVIOR
Authors: NATHAN BLACKMAN, THOMAS T. FLYNN, THOMAS P. MELICAN, JOHN G. NAPOLI, JAMES M. A. WEISS
Journal: American Journal of Psychiatry (1957)

A Social Maladjustment Study Unit was organized at Malcolm Bliss Psychiatric Hospital in July, 1956, to serve as an interdisciplinary research, teaching and consultation center focusing on the study, understanding and eventual social readjustment of individuals involved in aggressive antisocial or delinquent acts. Emphasis has been placed on collaboration of many disciplines representative of the community's assets. Thus lawyers, parole officers, judges, teachers, ministers and other group leaders have participated in the evaluation of each medico-legal problem, ranging from homosexuality to forgery, incest, and murder. In each case, an attempt is made to understand the motivation of the individual delinquent, the group alienation processes he presents, the possible measures toward his rehabilitation which might be effected within the community, and the probable intrapsychic determinants and interpersonal and community origins of his maladjustment (in terms of structuring group participation within the community toward preventive action in future similar cases). The research theme of the Study Unit stresses exploration of delinquency as an expression of social isolatedness, and antisocial acting out as a compulsive need to break through this sense of aloneness and isolatedness from meaningful social interaction; as well as investigation of the role of community action as a function of alertness to the emotional and social needs of the individual offender rather than the mere exercise of punitive or repressive measures.
Transient Global Amnesia-Reply
Authors: Paul A. Nausieda
Journal: JAMA (1979)

Like Dr Kennedy and his colleagues, we considered the possibility that TGA may be an epileptogenic condition. Electroencephalograms were obtained in 29 of the patients whose cases were reported in our series. In no case was the recording obtained during an amnestic episode, although most were obtained within a few days of the event. Review of these records showed 28 EEGs to be normal. One record demonstrated a right frontotemporal slow wave focus without spikes. A brain scan and carotid arteriogram failed to disclose any abnormalities, and no associated neurological deficits were present. During the subsequent two years, this patient was well, with no recurrence of amnesia. None of the patients in our series subsequently reported the occurrence of a convulsion during the follow-up period. No patients received anticonvulsant therapy.  Based on our experience, we do not believe that most cases of TGA are epileptic in origin. While
Inverse Association of Vitamin C with Cataract in Older People in India
Authors: Ravilla D. Ravindran, Praveen Vashist, Sanjeev K. Gupta, Ian S. Young, Giovanni Maraini, Monica Camparini, R. Jayanthi, Neena John, Kathryn E. Fitzpatrick, Usha Chakravarthy, Thulasiraj D. Ravilla, Astrid E. Fletcher
Journal: Ophthalmology (2011)

To examine the association between vitamin C and cataract in the Indian setting.Population-based cross-sectional analytic study.A total of 5638 people aged ≥60 years.Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.We found a strong association with vitamin C and cataract in a vitamin C-depleted population.The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Cellular Phones and Risk of Brain Tumors
Authors: H. Frumkin, A. Jacobson, T. Gansler, M. J. Thun
Journal: CA A Cancer Journal for Clinicians (2001)

As cellular telephones are a relatively new technology, we do not yet have long-term follow-up on their possible biological effects. However, the lack of ionizing radiation and the low energy level emitted from cell phones and absorbed by human tissues make it unlikely that these devices cause cancer. Moreover, several well-designed epidemiologic studies find no consistent association between cell phone use and brain cancer. It is impossible to prove that any product or exposure is absolutely safe, especially in the absence of very long-term follow-up. Accordingly, the following summary from the Food and Drug Administration Center for Devices and Radiological Health offers advice to people concerned about their risk: If there is a risk from these products--and at this point we do not know that there is--it is probably very small. But if people are concerned about avoiding even potential risks, there are simple steps they can take to do so. People who must conduct extended conversations in their cars every day could switch to a type of mobile phone that places more distance between their bodies and the source of the RF, since the exposure level drops off dramatically with distance. For example, they could switch to: a mobile phone in which the antenna is located outside the vehicle, a hand-held phone with a built-in antenna connected to a different antenna mounted on the outside of the car or built into a separate package, or a headset with a remote antenna to a mobile phone carried at the waist. Again the scientific data do not demonstrate that mobile phones are harmful. But if people are concerned about the radiofrequency energy from these products, taking the simple precautions outlined above can reduce any possible risk. In addition, people who are concerned might choose digital rather than analog telephones, since the former use lower RF levels.
Novel role of interleukin 7 in myelopoiesis: stimulation of primitive murine hematopoietic progenitor cells.
Authors: F W Jacobsen, O P Veiby, C Skjønsberg, S E Jacobsen
Journal: The Journal of Experimental Medicine (1993)

Interleukin 7 (IL-7) has been demonstrated to be an important regulator of the growth of B and T cell precursors as well as mature T cells, whereas IL-7 has been reported to have no direct myeloproliferative effects. Here we show that IL-7 potently and directly enhances colony stimulating factor-induced myeloid colony formation from Lin-Sca-1+ murine bone marrow progenitor cells, increasing the cloning frequency up to ninefold and cell numbers up to 50-fold, without affecting their ability to differentiate along the myeloid lineages In contrast, IL-7 has no effect on proliferation of committed Lin- myeloid progenitors. Thus, in addition to its established lymphopoietic potential, this study implicates a novel role of IL-7 in early myelopoiesis.
Meta-analysis of relation between cigarette smoking and stroke.
Authors: R. Shinton, G. Beevers
Journal: BMJ (1989)

There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.
Melanoma yield, number of biopsies and missed melanomas in a British teaching hospital pigmented lesion clinic: a 9-year retrospective study
Authors: None BATAILLE, None SASIENI, None CURLEY, None COOK, None MARSDEN
Journal: British Journal of Dermatology (1999)

The demand for pigmented lesion clinics (PLCs) is increasing in view of improved skin cancer awareness following public health education campaigns. These clinics offer an effective way of screening a large number of patients. However, there is no evidence, as yet, that they have an impact on mortality due to malignant melanoma. With the lack of follow-up inherent to these busy screening clinics, there is some concern that melanomas may be missed. This study reports on 7874 patient visits to a PLC in a teaching hospital between 1985 and 1994. In total, 1705 biopsies were performed over the 9-year period. Lesions were more likely to be biopsied in men compared with women. The yield for picking melanomas was one in 36 patient visits. The mean age of patients attending the PLC was 10 years less than the mean age for population-based melanomas. Melanoma thickness did not significantly change over the 9-year period. Only 0.2% of patients (14 cases) re-presented to the PLC for a second or third visit with a final diagnosis of melanoma, but for five of these patients, the interval between the two visits was over 2 years. Most of these ‘re-attending’ melanomas were early lesions. PLCs offer a fast, safe and efficient service for the screening of pigmented lesions but their role in reducing mortality due to malignant melanoma remains to be established. It is likely that these clinics have an important role in terms of public health education regarding sun avoidance and early recognition of skin cancer.
Estrogen-Like Properties of Fluorotelomer Alcohols as Revealed by MCF-7 Breast Cancer Cell Proliferation
Authors: Marleen Maras, Caroline Vanparys, Frederik Muylle, Johan Robbens, Urs Berger, Jonathan L. Barber, Ronny Blust, Wim De Coen
Journal: Environmental Health Perspectives (2005)

We investigated estrogen-like properties of five perfluorinated compounds using a combination of three in vitro assays. By means of an E-screen assay, we detected the proliferation-promoting capacity of the fluorotelomer alcohols 1H,1H,2H,2H-perfluorooctan-1-ol (6:2 FTOH) and 1H,1H,2H,2H-perfluoro-decan-1-ol (8:2 FTOH). The more widely environmentally distributed compounds perfluoro-1-octane sulfonate, perfluorooctanoic acid, and perfluorononanoic acid did not seem to possess this hormone-dependent proliferation capacity. We investigated cell cycle dynamics using flow cytometric analyses of the DNA content of the nuclei of MCF-7 breast cancer cells. Exposure to both fluorotelomer alcohols stimulated resting MCF-7 cells to reenter the synthesis phase (S-phase) of the cell cycle. After only 24 hr of treatment, we observed significant increases in the percentage of cells in the S-phase. In order to further investigate the resemblance of the newly detected xenoestrogens to the reference compound 17β-estradiol (E2), gene expression of a number of estrogen-responsive genes was analyzed by real-time polymerase chain reaction. With E2, as well as 4-nonylphenol and the fluorotelomer alcohols, we observed up-regulation of trefoil factor 1, progesterone receptor, and PDZK1 and down-regulation of ERBB2 gene expression. We observed small but relevant up-regulation of the estrogen receptor as a consequence of exposures to 6:2 FTOH or 8:2 FTOH. The latter finding suggests an alternative mode of action of the fluorotelomer alcohols compared with that of E2. This study clearly underlines the need for future in vivo testing for specific endocrine-related end points.
Predictors of poor outcome in patients w ith autoimmune hepatitis: A population-based study
Authors: Jing Hieng Ngu, Richard Blair Gearry, Chris Miles Frampton, Catherine A.M. Stedman
Journal: Hepatology (2013)

Abstract Autoimmune hepatitis (AIH) can lead to cirrhosis, hepatic failure, and death. We aimed to identify predictors of advanced liver fibrosis at presentation, predictors of incomplete response to initial immunosuppression, and predictors of poor liver-related outcomes in the population-based AIH cohort from Canterbury, New Zealand. Cases diagnosed after 1980 that fulfilled standard diagnostic criteria were included. Cases were censored at death or liver transplantation and had a median follow-up of 9 years. Analyses were performed with Cox proportional hazards regression and logistic binary regression. The times to event outcomes were summarized using Kaplan-Meier curves. A total of 133 AIH patients were included. Predictors for advanced liver fibrosis at diagnosis were age at presentation of ≤20 years or &gt;60 years ( P = 0.02), serum albumin &lt;36 g/L ( P &lt; 0.01), platelet &lt;150 U/L ( P &lt; 0.01), and International Normalized Ratio (INR) &gt;1.2 ( P &lt; 0.01). The only independent predictor for incomplete normalization of alanine aminotransferase (ALT) at 6 months was age at presentation ≤20 years. Independent predictors of poor liver-related outcomes were incomplete normalization of ALT at 6 months ( P &lt; 0.01), serum albumin &lt;36 g/L ( P &lt; 0.01), and age at presentation of ≤20 years or &gt;60 years ( P = 0.01). Kaplan-Meier estimates showed that 10-year adverse liver event-free survival was 80% for age at presentation ≤20 years and &gt;60 years, and 93% and 100% for age at presentation between 21-40 years and 41-60 years, respectively. Conclusion : Incomplete normalization of ALT at 6 months, low serum albumin concentration at diagnosis, and age at presentation of ≤20 years or &gt;60 years were significant independent predictors of liver-related death or requirement for liver transplantation. Histological cirrhosis at diagnosis was not associated with poor prognosis and did not influence the response to initial immunosuppressive treatment.
Akinesis becoming dyskinesis at high-dose dobutamine stress echocardiography: A marker of poor functional recovery after myocardial revascularization
Authors: Abdou Elhendy, Jan H. Cornel, Jos R.T.C. Roelandt, Ron T. van Domburg, Galal M. El-Said, Mohammed M. Ibrahim, Paolo M. Floretti
Journal: Journal of the American College of Cardiology (1996)
Local skin depigmentation due to local corticosteroid injection
Authors: R. Clayton
Journal: BMJ (1984)

incidence between first and second trimesters (x2=43 p< 0001) followed by an increased incidence in the third trimester (X2=26 p<0001).In view of these differences one wonders to what extent the association between life events and birthweight can be trusted to reflect causal relation.The differences in the incidence of life events are intriguing.A possible explanation is that a reported incidence reflects discomfort during pregnancy in terms of changing behaviour or changing the perception or reporting of life events.The discomfort of the first and third trimesters being contrasted by the relative well being of the second.To consider Dr Newton and Miss Hunt's data in this way would probably be more productive than in terms of the "stress" hypothesis.Demonstrable behavioural and psychological changes in pregnancy are of much broader interest and implication than the remote possi- bility of stress.
D2 DOPAMINE RECEPTORS IN TOURETTEʼS SYNDROME AND MANIC DEPRESSIVE ILLNESS
Authors: D. F. Wong, H. Singer, G. Pearlson, L. Tune, C. Ross, V. Villemagne, R. F. Dannals, J. M. Links, A. Wilson, H. Ravert, H. N. Wagner, A. Gjedde
Journal: Clinical Nuclear Medicine (1988)

Our previous studies have indicated elevated D2 Dopamine receptor (DR) density in psychiatric disorders, including schizophrenia. (Science 234,1558,1986). Elevated DR parameters have also been reported by others in MPTP-induced Parkinson's disease (Neurol 37:1575,1987). We are now studying adult subjects with Tourette's Syndrome and extending our studies of DSM III symptomatic Manic Depressive Illness and Schizophrenia. Two PET studies, one preceded by oral haloperidol (HAL), were performed for each subject to compute receptor density Bmax. We have now observed elevations in neuroleptic naive & previously treated but drug free patients, respectively: Schizophrenia (8/12);(5/6) and Manic-depressive illness (5/9);(3/6) and Tourette's Syndrome (1/1);(2/2). In Manic Depressive Illness, elevations were related to active psychosis, whereas values tended to be normal in patients without psychotic symptoms. All 3 Tourette's patients had elevated Bmax values; 27,36, and 1 appeared >100 pmoles/g, with higher values associated with greater clinical severity. These preliminary findings suggest that D2 Dopamine receptor elevations may occur in disorders with a prominent motor abnormality as well as illnesses, often characterized by psychotic symptoms. A common factor in all 3 disorders is that the DR antagonist HAL is a common treatment, and hence such D2 increases may relate to pathophysiology as well as therapeutic monitoring.
Hyperbaric Medicine in the US Air Force
Authors: Jefferson C. Davis
Journal: JAMA (1973)

The US Air Force hyperbaric chambers are used for treatment of the four disorders generally accepted as amenable to recompression or hyperbaric oxygenation. Ninety-four patients suffering from decompression sickness, air embolism, carbon monoxide intoxication, or gas gangrene have been treated. Forty-seven were military patients or their dependents, and 47 were civilians. The USAF series of 23 patients with surgically, bacteriologically proved spreading, diffuse clostridial myonecrosis brings the literature total of proved cases in patients treated with hyperbaric oxygenation during the past 11 years to 267. Recognized and treated early with a combined hyperbaric oxygen-débridement-antibiotic and supportive program, survival rates of those with gas gangrene should improve significantly.