tbuckley/cabot-search huggingface dataset:
Fatal toxicity of antidepressant drugs in overdose.
Authors: S Cassidy, J Henry
Journal: BMJ (1987)

A fatal toxicity index (deaths per million National Health Service prescriptions) was calculated for antidepressant drugs on sale during the years 1975-84 in England, Wales, and Scotland. The tricyclic drugs introduced before 1970 had a higher index than the mean for all the drugs studied (p less than 0.001). In this group the toxicity of amitriptyline, dibenzepin, desipramine, and dothiepin was significantly higher, while that of clomipramine, imipramine, iprindole, protriptyline, and trimipramine was lower. The monoamine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p less than 0.001). Of these newer drugs, maprotiline had a fatal toxicity index similar to that of the older tricyclic antidepressants, while the other newly introduced drugs had lower toxicity indices, with those for mianserin, nomifensine, trazodone, and viloxazine reaching significance. Provided that these drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity.
Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats
Authors: Pablo Ureña, Michael Mannstadt, Milan Hruby, Aníbal Ferreira, François Schmitt, Caroline Silve, Raymond Ardaillou, Bernard Lacour, Abdul-Badi Abou-Samra, Gino V. Segre, Tilman Drüeke
Journal: Kidney International (1995)
TWO CASES OF DIPHTHERIA WITH UNUSUAL COMPLICATIONS
Authors: J. J. Jervis, V. C. Martyn
Journal: BMJ (1914)

THe following cases, recently under our care in the Croydon Borough Isolation Hospital, are of special interest as slhowing two complications of diphtheria seldom met with in the practice of infectious fevers and not specifically mentioned in any of the standard textbooks dealing with this subject.CASE I.-Pulmonary Abscess.A girl, aged 9 years, was sent to the hospital as an ordinary case of laryngeal diplhtheria.The symptoms on admission were those of well-pronounced laryngeal obstruction; she was deeply cyanosed, breatbing was laboured with marked larvngeal stridor, and she displayed all the distressing symptoms of
Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels
Authors: Seungjin Shin, Lonnie D Shea
Journal: Molecular Therapy (2010)

Hydrogels can provide a controllable cell microenvironment for numerous applications in regenerative medicine, and delivery of gene therapy vectors can be employed to enhance their bioactivity. We investigated the delivery of lentiviral vectors from hydrogels, and employed the immobilization of lentivirus to hydroxylapatite (HA) nanoparticles as a means to retain and stabilize vectors within hydrogels, and thereby increase delivery efficiency. Entrapment of the vector alone within the hydrogel maintained the activity of the virus more effectively compared to the absence of a hydrogel, and release was slowed with an increasing solid content of the hydrogel. Association of the lentivirus with HA increased the activity of the complexes, with HA increasing the virus activity for 72 hours. Cells seeded onto lentivirus–HA-loaded hydrogels had a decreased number of infected cells outside of the hydrogel relative to the absence of HA. In vivo studies with collagen hydrogels loaded with lentivirus and HA-lentivirus demonstrated sustained and localized transgene expression for at least 4 weeks, with increased expression using the lentivirus–HA complex. This strategy of nanoparticle immobilization to stabilize and retain vectors is broadly applicable to hydrogels, and may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine. Hydrogels can provide a controllable cell microenvironment for numerous applications in regenerative medicine, and delivery of gene therapy vectors can be employed to enhance their bioactivity. We investigated the delivery of lentiviral vectors from hydrogels, and employed the immobilization of lentivirus to hydroxylapatite (HA) nanoparticles as a means to retain and stabilize vectors within hydrogels, and thereby increase delivery efficiency. Entrapment of the vector alone within the hydrogel maintained the activity of the virus more effectively compared to the absence of a hydrogel, and release was slowed with an increasing solid content of the hydrogel. Association of the lentivirus with HA increased the activity of the complexes, with HA increasing the virus activity for 72 hours. Cells seeded onto lentivirus–HA-loaded hydrogels had a decreased number of infected cells outside of the hydrogel relative to the absence of HA. In vivo studies with collagen hydrogels loaded with lentivirus and HA-lentivirus demonstrated sustained and localized transgene expression for at least 4 weeks, with increased expression using the lentivirus–HA complex. This strategy of nanoparticle immobilization to stabilize and retain vectors is broadly applicable to hydrogels, and may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.
Paracrine stimulation of vascular smooth muscle proliferation by diadenosine polyphosphates released from proximal tubule epithelial cells
Authors: V. Jankowski, S. Karadogan, R. Vanholder, J.-R. Nofer, S. Herget-Rosenthal, M. van der Giet, M. Tölle, T.N.A. Tran, W. Zidek, J. Jankowski
Journal: Kidney International (2007)
Production of metabolic products of arachidonic acid during cell-cell interactions
Authors: Aaron J. Marcus, Lenore B. Safier, M.Johan Broekman, Harris L Ullman, Naziba Islam, Tania C. Sorrell, Charles N. Serhan, Gerald Weissmann, Thomas D. Oglesby, Robert R. Gorman
Journal: Journal of Allergy and Clinical Immunology (1984)
Epistatic Effects of Potassium Channel Variation on Cardiac Repolarization and Atrial Fibrillation Risk
Authors: Stefan A. Mann, Robyn Otway, Guanglan Guo, Magdalena Soka, Lina Karlsdotter, Gunjan Trivedi, Monique Ohanian, Poonam Zodgekar, Robert A. Smith, Merridee A. Wouters, Rajesh Subbiah, Bruce Walker, Dennis Kuchar, Prashanthan Sanders, Lyn Griffiths, Jamie I. Vandenberg, Diane Fatkin
Journal: Journal of the American College of Cardiology (2012)
Prognostic Factors After Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
Authors: Nabil P. Rizk, Venkatraman E. Seshan, Manjit S. Bains, David H. Ilson, Bruce D. Minsky, Laura Tang, Valerie W. Rusch
Journal: Journal of Thoracic Oncology (2007)
Manufacturer admits increase in suicidal behaviour in patients taking paroxetine
Authors: Jeanne Lenzer
Journal: BMJ (2006)

GlaxoSmithKline announced last week that they had found an increase in suicidal behaviour in adults taking paroxetine (Paxil/Seroxat) compared with placebo. The conclusion was based on an analysis of patients aged 18-64 years in clinical trials.

The researchers found that 0.32% (11/3455) of people taking paroxetine for depression attempted suicide compared with 0.05% (1/1978) of depressed patients taking placebo (odds ratio 6.7, 95% confidence interval 1.1 to 149.4; P=0.058). One person in the paroxetine group successfully killed themselves. GlaxoSmithKline said the data should be interpreted with caution and that the “overall risk-benefit of paroxetine in the treatment of adult patients with MDD [major depressive disease] remains positive.”

The Glaxo study confirms the suggested link …
A Case of Dissecting Aortic Aneurysm
Authors: R. C. Gledhill
Journal: BMJ (1947)

this time only a scar remained at the site of the carbuncle on his neck; the one on his thigh had completely aborted.Case 7.-Mr.K., aged 41, had had a carbuncle on his right forearm for five days.He complained of pain up the arm and in the axilla.He was anxious to return to work as soon as possible, and 200,000 units of penicillin was given twice daily for three days, and a single dose on the fourth day.By this time the swelling had nearly subsided and the carbuncle was discharging freely.
Studies of liver insulin receptors in non-obese and obese human subjects.
Authors: P Arner, K Einarsson, L Backman, K Nilsell, K M Lerea, J N Livingston
Journal: Journal of Clinical Investigation (1983)

The insulin-binding isotherms and the structural composition of human liver insulin receptors were examined by using plasma membranes that were prepared from liver biopsies of nine non-obese and 10 obese subjects undergoing elective surgery. The insulin-binding characteristics of liver membranes from non-obese subjects were quite similar to those previously described in rat liver membranes. However, when the membranes from obese subjects were compared with the non-obese group, insulin-binding activity was reduced by 50% (P less than 0.01). The reduction in obesity resulted primarily from a decrease in total receptor number, although a small decrease in receptor affinity was also observed. Insulin binding was not correlated with sex or with the fasting plasma insulin level. The insulin-binding sites of liver membranes were affinity-labeled with 125I-insulin and the cross-linking reagent, disuccinimidyl suberate. The liver membranes from both the non-obese and the obese group had heterogenous (nonreduced) insulin-binding species of 300,000, 260,000, and 150,000 mol wt, which were again comparable to the findings reported in rat liver. Sulfhydryl reduction demonstrated a major sub-unit of 125,000 and a minor component of 40,000-45,000 in both groups. These results indicate a close similarity between the hepatic insulin receptor of man and the more intensely studied rat hepatic receptor. Obesity in human subjects is associated with a loss of hepatic insulin receptors. This alteration may contribute to the insulin resistance reported in this organ as well as to obesity-mediated glucose tolerance.
Malrotation Demonstrated on Gastric Emptying Study
Authors: STUART C. MORRISON, JAMES K. O'DONNELL
Journal: Clinical Nuclear Medicine (1998)

Gastric emptying study was performed following demonstration of gastroesophageal reflux in a child with persistent vomiting. The dynamic study was performed with liquid formula labeled with Tc-99m sulfur colloid. Images are shown at 30 minutes and 60 minutes and clearly demonstrate all of the small bowel to the right of midline. Subsequent upper GI barium study confirmed the diagnosis of malrotation. The upper GI series remains the "gold standard" for the diagnosis of malrotation, but this diagnosis can be suggested from other studies including ultrasound and, more rarely, as described in this case, gastric emptying studies.
Studies of Factors V and VIII:C in an animal model of disseminated intravascular coagulation.
Authors: A R Giles, M E Nesheim, K G Mann
Journal: Journal of Clinical Investigation (1984)

An experimental animal model of disseminated intravascular coagulation (DIC) induced by the co-infusion of coagulant-active phospholipid and activated Factor X (Factor Xa) is described. The infusion of Factor Xa at a dose of 6.6 X 10(-12) mol/kg with phosphatidylcholine/phosphatidylserine (PCPS) lipid vesicles at a dose of 4.0 X 10(-8) mol/kg was associated with significant falls in the levels of fibrinogen and Factors V and VIII, and a bleeding diathesis developed. Assays of Factors V and VIII were performed by a one-stage prothrombin time and activated partial thrombin time system, respectively. In additional experiments, the effect of the same dose combination of Factor Xa/PCPS on Factor V kinetics was studied by preinfusing 125I-labeled Factor V. After Factor Xa/PCPS infusion, Factors VIII and V were reduced at 2 min by 90 and 50% of the preinfusion levels, respectively, and at 1 h by 80 and 75%, respectively. During the same period, there was little change in the total circulating radioactivity. Autoradiography indicated small but detectable levels of circulating proteolytic products of Factor V that comigrated with peptides obtained by the incubation of Factor V with Factor Xa and activated protein C. The majority of radioactivity remained associated with the intact single-chain precursor Factor V. These observations suggested maintenance of the precursor pool after the onset of DIC. This was confirmed by performing two-stage assays of Factors V and VIII, whereby each was completely converted to the active cofactor, i.e., Va and VIII:Ca, by preincubation of the test sample with thrombin before assaying in a one-stage system as before. The Factor V levels assayed by the two-stage procedure did not change appreciably over 1 h. The Factor VIII levels fell but corrected within 1 h at a time when the level measured by a one-stage assay remained depressed. These results indicate that in the dog, infusion of Factor Xa/PCPS induces changes characteristic of DIC, and this is associated with the appearance of Factor V peptides characteristic of the expression of Factor Xa and activated protein C-like activities. The differences noted between the one-stage and two-stage assays suggest that the one-stage assay is measuring the activated fraction of each cofactor and not the total level of the available precursor for each activated species. The results suggest a close correlation between the activated fraction of both cofactors and the hemostatic abnormality that occurs in DIC.
Cerebral Infarction in Child Abuse Diagnosis by Technetium-99m Methylene Diphosphonate Skeletal Scintigraphy
Authors: CHARLES M. GLASIER, JOANNA J. SEIBERT, SUSAN L. WILLIAMSON
Journal: Clinical Nuclear Medicine (1987)

A 6-month-old physically abused child had increased uptake of Tc-99m MDP in the parietal and occipital lobes of the brain on skeletal scintigraphy. Subsequent cranial computed tomography (CT) showed diffuse encephalomalacia and dystrophic brain calcification corresponding to the areas of increased activity on scintigraphy. Cranial images on bone scintigrams in known or suspected cases of child abuse should be closely examined for areas of increased activity that could represent infarction.
Medical tests help reduce sentence of woman accused of murder
Authors: F. Turone
Journal: BMJ (2011)

A criminal court in Como, northern Italy, has accepted genetic and neuroscientific tests, including neuroimaging, as evidence that a young murderer was only partly responsible for her crime because of reduced capacity.

Previous testimony in the case from two clinical evaluations had come to the opposite conclusion, but the judge was finally convinced by evidence from a third evaluation, presented by the defence, that involved neuroscientific and genetic tests in addition to a thorough psychiatric examination. The judge considered these conclusions to be “more reliant on objectivity and evidence” than those that were based only on a traditional clinical approach.

The sentence given to …
The Laboratory Diagnosis of Syphilis
Authors: HAROLD W. JAFFE
Journal: Annals of Internal Medicine (1975)

Although new tests for syphilis, as well as new applications of standard tests, continue to appear, the usefulness of several of these procedures has not been determined. When the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test is used to screen for syphilis, the proportion of positive results that are true positives decreases. The value of modified FTA tests in the diagnosis of neurosyphilis and congenital syphilis remains unproved. Although not studied as extensively as the standard tests, several newer methods—the direct fluorescent antibody test for Treponema pallidum (DFATP), the Rapid Plasma Reagin (RPR) card test, and the microhemagglutination test for T. pallidum (MHA-TP)—may have certain advantages. To be of optimal diagnostic value, tests for syphilis must be selected according to the clinical situation.
The Synergistic Effect of Heredity and Exposure to Second-Hand Smoke on Adult-Onset Asthma
Authors: Taina K. Lajunen, Jouni J. K. Jaakkola, Maritta S. Jaakkola
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Identification of the subpopulation especially susceptible to the adverse effects of second-hand smoke exposure (SHS) would be useful for preventive actions and interventions.To investigate whether asthmatic heredity indicates susceptibility to the effects of SHS on the risk of adult-onset asthma.A population-based incident case-control study of clinically defined adult-onset asthma and randomly drawn control subjects (adults 21-63 yr old) from a geographically defined area in South Finland. After excluding current and ex-smokers there were 226 cases and 450 disease-free control subjects.Our outcome measure was new adult-onset asthma. Parental asthma and recent SHS had a synergistic effect on the risk of asthma, the adjusted odds ratio being 1.97 (95% confidence interval, 1.12-3.45) for SHS; 2.64 (1.65-4.24) for parental asthma; and 12.69 (3.44-46.91) for their joint effect (relative excess risk due interaction, 9.08 [-0.22 to 43.18]). Synergistic effect followed a dose-dependent pattern with both recent and cumulative SHS exposures, with relative excess risk due interaction for parental asthma and over 100 SHS cigarette-years of 6.17 (0.57-19.16).This is the first study showing that individuals with asthmatic heredity have a considerably increased risk of adult-onset asthma when exposed to SHS. SHS exposure has dose-dependent synergism with family history of asthma, the joint effect being stronger with higher exposure levels. Avoiding SHS could be an important preventive measure for reducing the risk of adult-onset asthma among those with asthmatic heredity. Asking about family history of asthma is a useful tool for identifying these susceptible individuals in clinical and preventive settings.
Seasonal variation in the patient diagnosis of primary biliary cirrhosis: Further evidence for an environmental component to etiology
Authors: Richard J.Q. McNally, Peter W. James, Samantha Ducker, Oliver F.W. James
Journal: Hepatology (2010)

The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987-2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody–positive titer ≥1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O = 115, E = 84.7, O/E = 1.36; P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012). Conclusion: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC. (HEPATOLOGY 2011)
Nutritional Cirrhosis in Man?
Authors: Hans Popper, Fenton Schaffner
Journal: New England Journal of Medicine (1971)

Many animal models have been studied in which dietary variations produce liver injury, including cirrhosis. By extrapolation, malnutrition, particularly deficiencies of protein and vitamins, has long been considered an important factor in human cirrhosis when no evidence existed for another etiology. Recent investigations cast doubt on the concept of nutritional cirrhosis if we consider alcohol a toxic agent rather than a nutritional one.1 Protein-calorie malnutrition or kwashiorkor produces fatty liver in children, with some portal fibrosis but not cirrhosis, and its dangerous effects are primarily related to cerebral dysfunction. Even long standing steatosis has not been shown to lead to . . .
144. Magnetically Responsive Nanoparticles Enhance Adenoviral Gene Delivery in Cultured Smooth Muscle Cells
Authors: Michael Chorny, Ilia Fishbein, Ivan Alferiev, Origene Nyanguile, Robert J. Levy
Journal: Molecular Therapy (2006)

Replication deficient adenoviruses (Ad) are extensively investigated for gene delivery applications due to a number of advantages as gene vectors, including high transgene expression and their ability to transduce both quiescent and dividing cells. Their clinical use is however limited by therapeutically suboptimal transduction levels in cell types expressing low levels of Coxsackie- Ad receptor (CAR), as well as systemic toxicity associated with their distribution to non-target tissues. Targeted delivery achievable with Ad complexed with biodegradable magnetically responsive nanoparticles (NP) may therefore be instrumental for improving both safety and efficiency of these vectors. Our hypothesis was that magnetically driven delivery of Ad affinity-bound to biodegradable NP can substantially increase transgene expression in CAR deficient smooth muscle cells in culture. Iron oxide laden NP sized 340±30 nm were formulated from polylactide and coated with benzophenone functionalized photoreactive polymer providing the means to covalently attach the D1 domain of the CAR to the NP surface. GFP-encoding Ad was complexed with NP fluorescently labeled using PLA-BODIPY 546/570 conjugate and applied to rat aortic smooth muscle cells (A10) for 15 min in the presence of magnetic field at respective doses of 0-9×107 and 0-2.3 μg per well. NP cellular uptake and transgene expression were assayed fluorimetrically in live cells 24-120 hr post treatment using λex/λem of 540 nm/575 nm and 485 nm/535 nm, respectively. The efficiency of NP association with cells within the 15 min incubation period was high, and independent of the NP dose (96±3% and 87±11% complete for doses of 1.1 and 2.3 μg per well), while the measured intracellular level was directly NP dose dependent in the studied NP dose range. The transgene expression mediated by the complexes was directly dependent on both Ad and NP dose and peaked at 72-96 hr decreasing by ∼40% by the 120 hr timepoint. While Ad alone did not result in high transgene levels in the CAR deficient A10 cells at any timepoint (less than 7 relative fluorescence units, RFU), NP-Ad complexes increased the transgene expression 90 to 450-fold for the lowest and the highest NP doses (554 and 2788 RFU at 0.6 and 2.3 μg per well, respectively) without significant adverse effects on the cell viability. NP covalently modified with D1 were on average 2.5-fold more effective than NP prepared without the covalent modification notwithstanding their comparable cell uptake rates. It is concluded that magnetically driven Ad delivery in the form of an affinity complex with biodegradable NP provides the means to significantly increase gene transfer rates in cultured smooth muscle cells.
Time to legalise assisted dying? : Summary of responses
Authors: Birte Twisselmann
Journal: BMJ (2005)

Two weeks ago Delamothe asked in his Editor's choice: “Are you for, against, or—like the BMA…—neutral?” The subject was assisted dying, and the flood of responses sparked by Editor's choice and the five Education and debate articles made it very clear that neutrality was not a concept that the many respondents found acceptable, conceivable, or even possible.1–6 A notable complaint was the lack of balance in the views presented, which had been aggravated by some infelicitous editing of the week's homepage. Responders were mainly doctors from the United Kingdom, although several barristers, philosophers, and a nurse …
Factors affecting outcomes in penetrating diaphragmatic trauma
Authors: Chien-Hung Liao, Chih-Po Hsu, I-Ming Kuo, Chun-Hsiang Ooyang, Shang-Yu Wang, Jen-Fu Huang, Chih-Yuan Fu, Shang-Ju Yang, Shih-Ching Kang
Journal: International Journal of Surgery (2013)