tbuckley/cabot-search huggingface dataset:
19F magnetic resonance spectroscopy investigation in vivo of acute and steady-state brain fluvoxamine levels in obsessive-compulsive disorder
Authors: W L Strauss, M E Layton, C E Hayes, S R Dager
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to investigate the pharmacokinetics of fluvoxamine in the human brain by using fluorine-19 magnetic resonance spectroscopy (19F MRS) and to assess the relationships among fluvoxamine brain levels, fluvoxamine plasma levels, and clinical efficacy.Eight subjects with DSM-IV obsessive-compulsive disorder were entered into a prospective, open-label treatment trial of fluvoxamine. 19F MRS measurements of whole brain drug and metabolite concentrations and spin-lattice (T1) relaxation times were performed serially in seven subjects for up to 5 months. A psychiatric determination of clinical response and a blood sample for plasma fluvoxamine measurement were obtained at each 19F MRS session.The subjects achieved steady-state brain concentrations of fluvoxamine within 30 days after consistent daily dosing, as determined by stabilization of brain fluvoxamine concentrations. The mean brain-to-plasma ratio at steady state was 24 to 1. Brain fluvoxamine T1 values from 140 to 230 msec were observed. All but one subject experienced substantial improvement in symptoms. The one nonresponder exhibited several-fold higher plasma and brain fluvoxamine levels.Brain fluvoxamine levels were substantially higher than plasma levels. Steady-state brain levels correlated to plasma levels but not to dose. Systematic assessment of treatment response in relation to brain or plasma fluvoxamine level was not feasible because of the marked and rapid clinical response during open-label treatment. These data suggest that fluvoxamine attains brain steady-state levels substantially faster than fluoxetine, with corresponding clinical implications.
Analysis of lung volume restriction in patients with respiratory muscle weakness.
Authors: A De Troyer, S Borenstein, R Cordier
Journal: Thorax (1980)

We investigated pulmonary mechanics in 25 patients, 9 to 55 years of age, with a variety of generalised neuromuscular diseases and variable degrees of respiratory muscle weakness. The average degree of inspiratory muscle force was 39.2% (range 8-83%) of predicted. The lung volume restriction far exceeded that expected for the degree of muscle weakness: the observed decrement in respiratory muscle force should, theoretically, decrease vital capacity to 78% of its control value, while the mean VC in our patients was only 50% of predicted. Analysis of lung pressure-volume curves indicated that the two principal causes of the disproportionate loss of lung volume were a reduction in lung distensibility probably caused by widespread microatelectasis, and a decrease in the outward pull of the chest wall. Because it reflects both direct (loss of distending pressure) and secondary (alterations in the elastic properties of the lungs and chest wall) effects of respiratory muscle weakness on lung function, we conclude that, in these patients, the vital capacity remains the most useful measurement to follow evolution of the disease process or response to treatment.
Arterial Behavior and Blood Circulation in the Brain
Authors: Charles M. Poser
Journal: JAMA (1987)

This unusual volume represents the work of one of the leading investigators of cerebrovascular physiology and pathology in the Soviet Union. His ideas are not well known to Western science. Many of them are unorthodox, and in many instances he raises more questions than he answers. His book provides a most welcome and rare glimpse into an important area of research as it is carried out in the Georgian Republic of the Soviet Union. The book consists of the results of many experiments by the author and his collaborators as well as illustrative, penetrating, and at times provocative discussions of the theoretical aspects of the problems. The author is familiar with the Western literature on this complicated subject and draws freely on such publications, which he skillfully incorporates into many of his theoretical proposals. His belief that cerebral arteries, arterioles, and capillaries may under certain circumstances respond to specific controls,
Social deprivation in Duchenne muscular dystrophy: population based study
Authors: K. Bushby, S. Raybould, S. O'Donnell, J. G Steele
Journal: BMJ (2001)

We excluded 57 minor fractures and one haemarthrosis from further analysis as they could be argued to be more serious injuries.We analysed attendance for the remaining 364 case-control pairs only.Case children attended significantly fewer half days in school after injury than control children (7.38 v 9.40, P < 0.001).Deprivation scores for matched pairs did not differ significantly, and there was no association between missed time at school and deprivation score.Mean half day attendance in the week preceding injury did not differ significantly between case children and control children (9.25 v 9.59, P > 0.1).
Inferring HIV Transmission Dynamics from Phylogenetic Sequence Relationships
Authors: Christopher D Pilcher, Joseph K Wong, Satish K Pillai
Journal: PLoS Medicine (2008)

Despite the range of resources directed at understanding the HIV pandemic over the past 25 years, surprisingly little is known about how HIV infection spreads through populations. Unlike some other infectious diseases, acute infection with HIV is difficult to identify. HIV disease most often manifests years after the transmission event. Together with the special challenges involved in determining exposures related to sexual behavior or drug use, all of these factors have made it difficult to apply the tools of traditional epidemiologic investigation. Recent antibody testing strategies to identify incident HIV for surveillance programs have met with limited success [1]. Key questions that remain unanswered by empirical data include the role of acute infections in sustaining the current pandemic, and the effects of antiretroviral treatment programs on transmission of drug-resistant and drug-susceptible strains of HIV. Without really understanding how HIV spreads, it is difficult to optimize prevention or control strategies.

As effective anti-HIV therapies emerged over the past decade, clinical care and surveillance programs have increasingly emphasized the importance of testing for resistance to antiretroviral drugs. This most commonly involves sequencing of viral genes for resistance mutations. The rapid expansion of this HIV genotyping has predictably resulted in creation of vast databases that now contain viral sequence information. The new study by Andrew Leigh Brown and colleagues in this issue of PLoS Medicine [2] shows that modern analytic tools may yield important new insights into HIV transmission dynamics from the information routinely collected in such sequence databases.

Linked Research Article
This Perspective discusses the following new study published in PLoS Medicine:

Lewis F, Hughes GJ, Rambaut A, Pozniak A, Leigh Brown AJ (2008) Episodic sexual transmission of HIV revealed by molecular phylodynamics. PLoS Med 5(3): e50. doi:10.1371/journal.pmed.0050050

Using viral genotype data from HIV drug resistance testing at a London clinic, Andrew Leigh Brown and colleagues derive the structure of the transmission network through phylogenetic analysis.
Complete Rupture of Uterus with Subsequent Pregnancy
Authors: D. H. Finlayson
Journal: BMJ (1956)

In the rat passive Heymann nephritis model of membranous nephropathy, complement C5b-9 induces sublethal glomerular epithelial cell (GEC) injury and proteinuria. C5b-9 activates cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>), and products of cPLA<sub>2</sub>-mediated phospholipid hydrolysis modulate GEC injury and proteinuria. In the present study, we demonstrate that C5b-9 activates c-Jun N-terminal kinase (JNK) in cultured rat GECs and that JNK activity is increased in glomeruli isolated from proteinuric rats with passive Heymann nephritis, as compared with control rats. Stable overexpression of cPLA<sub>2</sub> in GECs amplified complement-induced release of arachidonic acid (AA) and JNK activity, as compared with neo (control) GECs. Activation of JNK was not affected by indomethacin. Incubation of GECs with complement stimulated production of superoxide, and pretreatment with the antioxidants, <i>N</i>-acetylcysteine, glutathione, and α-tocopherol as well as with diphenylene iodonium, an inhibitor of the NADPH oxidase, inhibited complement-induced JNK activation. Conversely, H<sub>2</sub>O<sub>2</sub> activated JNK, whereas exogenously added AA stimulated both superoxide production and JNK activity. Overexpression of a dominant-inhibitory JNK mutant or treatment with diphenylene iodonium exacerbated complement-dependent GEC injury. Thus, activation of cPLA<sub>2</sub> and release of AA facilitate complement-induced JNK activation. AA may activate the NADPH oxidase, leading to production of reactive oxygen species, which in turn mediate the activation of JNK. The functional role of JNK activation is to limit or protect GECs from complement attack.
FDG PET/CT for Assessing Therapy Response in Primary Thyroid Lymphoma
Authors: Eugene C. Lin
Journal: Clinical Nuclear Medicine (2007)

A 57-year-old man with a history of Hashimoto thyroiditis was diagnosed with a diffuse large B-cell lymphoma of the thyroid. He underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT scan) for staging, which demonstrated intense uptake in the thyroid lymphoma. After 3 cycles of chemotherapy followed by radiation to the thyroid, a follow-up PET/CT scan demonstrated complete resolution of the activity. FDG PET/CT is a well-established modality for assessing therapy response in lymphoma. It may also be useful in assessing therapy response in rare types of lymphomas as illustrated by this case.
Careers in Cardiovascular Outcomes Research
Authors: Mikhail Kosiborod, John A. Spertus
Journal: Circulation (2009)

best understand the field and goals of outcomes research, it is important to appreciate the challenges that confront our healthcare system.Although considerable advances in patient care have been made over the last several decades, patients, physicians, and payers continue to struggle with rising costs and inefficiencies, poor application of evidence to clinical care, fragmentation, misaligned incentives, disparities, suboptimal patient safety, and lack of patient-centeredness.In its seminal 2001 report, Crossing the Quality Chasm: A New Health System for the Twenty-first Century, the Institute of Medicine concluded that the US healthcare system has fallen far short of its potential to deliver care in a safe, timely, equitable, efficient, evidence-based or patient-centered manner. 1 They called for a complete redesign of the way in which we currently practice and deliver care.The field of outcomes research is ideally positioned to address most of these challenges.Outcomes research focuses on what is ultimately achieved by our efforts in healthcare.It seeks not only to describe the "end-result of healthcare" (patient outcomes) and its determinants but also to develop solutions to improve the outcomes by aligning the needs of patients with the performance of physicians and the healthcare system with the use of available resources. 2,3The field of outcomes research ranges from everyday clinical decision making that affects individual physicians and patients to population science, health economics, and policy.As such, outcomes research lies at the interface of multiple scientific disciplines, including clinical epidemiology, biostatistics, qualitative research, behavioral science, organizational theory, ethics, decision analysis, health system economics, health policy, health informatics, and the sciences of quality improvement and implementation research.Understanding and integrating these multiple disciplines can accelerate the pace and application of insights into practice.Therefore, to be a successful outcomes researcher, one should ultimately be contributing toward the process of improving clinical care.Although the full cycle of improvement requires multiple stages and participants, a prospective investigator must be able to identify critical issues in patient care and health policy, crystallize these issues and possible solutions, study the identified components of care, summarize and disseminate the findings, and then contribute toward the implementation of potential solutions, often studying the
Terutroban, a TP-receptor antagonist, reduces portal pressure in cirrhotic rats
Authors: Eugenio Rosado, Aina Rodríguez-Vilarrupla, Jorge Gracia-Sancho, Dinesh Tripathi, Héctor García-Calderó, Jaume Bosch, Juan Carlos García-Pagán
Journal: Hepatology (2013)

Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2 /prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride (CCl4 ) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction), and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4 -cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4 -cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (α-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway.Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis. This effect is due to decreased hepatic resistance, which in CCl4 -cirrhotic rats was linked to decreased hepatic fibrosis, but not in BDL rats, in which the main mediator appeared to be an enhanced eNOS-dependent vasodilatation, which was not liver-selective, as it was associated with decreased arterial pressure. The potential use of terutroban for portal hypertension requires further investigation.
IMMUNOLOGICAL MEMORY IN VITRO
Authors: Gordon N. Radcliffe, Michael A. Axelrad
Journal: The Journal of Experimental Medicine (1971)

The immune responses to sheep erythrocytes of mouse spleen cell suspensions from immune and nonimmune donors were compared in vitro. In vivo immunity was only transiently reflected in vitro, and 8 wk after in vivo immunization the responses of cultures from immunized and nonimmunized mice were virtually identical. There appeared to be two mechanisms for an antibody response to sheep erythrocytes. The first was responsible for the early primary response and is unmodified in the immune animal though contributing little to subsequent in vivo responses due to its suppressibility by specific antibody. The second was expressed in the in vivo secondary response but not on in vitro challenge of spleen cells from mice immunized many weeks previously; spleen cell cultures from such immune mice, freed from the antibody of the in vivo environment, once again demonstrate a pure primary-type response.
Royal College of Physicians — A New Journal — As Others See Us — Referring Patients
Authors: John Lister
Journal: New England Journal of Medicine (1967)

SINCE its move into the new building in Regents Park, the activities of the Royal College of Physicians have been greatly extended. In particular the scope of the scientific meetings has been widened, and throughout the year there are seminars for residents and interns as well as conferences for consultants and specialists. A further aim of the College is to exercise its influence in maintaining a link between diverging specialties at a time when medicine is tending to fragment. The joint meeting in Boston next year between the Americal College of Physicians and the Royal College of Physicians is keenly . . .
Bipolarity is important during treatment with antidepressants
Authors: Daniel J Smith, James T Walters
Journal: BMJ (2007)

suicide riskBipolarity is important during treatment with antidepressants Rubino et al have identified that most (if not all) of the excess risk of suicide in a group of patients treated with venlafaxine could be explained by a higher burden of risk factors for suicide.It may be true that this group of patients had more severe or "difficult to treat" unipolar depression, but it is also possible that bipolar features in this group may be responsible for the observed raised rates of suicidality.Perhaps because of limitations of space, the authors do not discuss this as a possibility, despite an adjusted relative risk of completed suicide of 4.94 (95% confidence interval 1.30 to 18.84) for "past history of bipolar disorder" (table 3). 1 Recent work shows that at least 50% of difficult to treat unipolar depressed patients may have an undetected bipolar disorder, 2 and it is now well documented that antidepressant monotherapy for bipolar depression runs a high risk of precipitating hypomanic or mixed affective states, 3 which have been strongly associated with self harm and completed suicide. 4 It is also the case that venlafaxine seems more likely than other antidepressants to precipitate a switch into hypomania or mania in bipolar depression. 5Furthermore, many of the variables reported by Rubino et al could be considered to point towards high levels of bipolarity in the venlafaxine treated group, including higher rates of a family history of psychiatric disorder, more frequent prescription of antipsychotics and mood stabilisers, a history of non-response to several different antidepressants, and more frequent lifetime depressive episodes.
Raymond Clive Gledhill
Authors: J. Gledhill
Journal: BMJ (2010)

Raymond Clive Gledhill was born in Leeds, and at the age of 9, his father (a tailor’s presser) died. He won a scholarship to the City of Leeds School and later a further scholarship to study medicine at Leeds University. At the start of his career, his ambition was to become a hospital physician, and he followed this path to registrar level. However, competition for posts was high, and, at the age of 32, he changed to psychiatry, training at the Maudsley and King’s …
Renal Vein Thrombosis, Nephrotic Syndrome, and Systemic Lupus Erythematosus
Authors: GERALD B. APPEL
Journal: Annals of Internal Medicine (1976)

We report here four cases of systemic lupus erythematosus associated with the nephrotic syndrome and renal vein thrombosis and review six familiar cases previously noted in the literature. Renal biopsy in each of our cases showed changes consistent with the membranous type of lupus nephropathy. We discuss the exclusive appearance of this pattern in relation to renal vein thrombosis in other forms of renal disease. The occurance of renal vein thrombosis in patients with systemic lupus erythematosus and the nephrotic syndrome supports the evidence that the thrombosis is a complication rather than a cause of the nephrotic syndrome. The presence of pleuritic pain in a patient with systemic lupus erythematosus and the nephrotic syndrome should alert the clinician to the possibility of renal vein thrombosis and pulmonary emboli. With appropriate diagnosis and anticoagulation therapy, our patients had a benign course during 7 to 48 months of follow-up.
Ungewöhnliche endoskopische Untersuchungs-technik zur präoperativen Diagnostik bei Ösophagusstriktur
Authors: H. Wiendl, A. Harlacher, E. Stuchlik
Journal: Endoscopy (1972)

Case report of complete cicatricial stricture of the esophagus. A preoperative statement about the length of stenosis and the type and extent of surgery was possible by means of an unusual technique of esophagoscopy via a gastric fistula only.
Serotonin-Induced Coronary Contraction Increases After Blood Cardioplegia-Reperfusion : Role of COX-2 Expression
Authors: C. Metais, J. Li, J. Li, M. Simons, F. W. Sellke
Journal: Circulation (1999)

Coronary contraction has been implicated in causing suboptimal myocardial function after coronary bypass surgery. Addition of blood to cardioplegic solutions has been shown to improve endothelial function after cardioplegia. In this study, the effects of blood cardioplegia and brief reperfusion on vascular reactivity in patients with coronary artery disease and the expression (mRNA and protein) of enzymes involved in vasomotor regulation were examined.The atrial appendages of patients undergoing coronary artery surgery were harvested before cardiopulmonary bypass (control, n=8) and after bypass from a nonischemic tissue atrial segment exposed to cold, hyperkalemic blood cardioplegia (mean, 60 minutes) and a brief period (10 minutes) of reperfusion (CP-Rep, n=8). Responses of atrial arterioles were studied in vitro with video-microscopy. Reverse-transcriptase polymerase chain reaction and Western blotting were used to examine the expressions and protein content, respectively, of enzymes involved in vasomotor regulation. Serotonin caused a minimal dilation under baseline conditions but after CP-Rep elicited a potent contractile response that was inhibited in the presence of the selective inducible cyclooxygenase (COX-2) inhibitor NS398. Substance P caused an endothelium-dependent relaxation of atrial arterioles through release of nitric oxide, and ADP caused relaxation mediated through release of prostaglandins. After CP-Rep, relaxation to substance P was impaired, whereas endothelium-independent relaxation to nitroprusside and response to ADP were unchanged. Expression and protein level of COX-2 were significantly increased after CP-Rep. In contrast, expression of inducible (nitric oxide synthase-2) or constitutive endothelial (nitric oxide synthase-3) nitric oxide synthase, prostacyclin synthase, and constitutive cyclooxygenase (COX-1) were not altered after CP-Rep.CP-Rep increases serotonin-induced contraction of human microvessels caused by the release of products of COX-2 and the impaired release of nitric oxide. These findings have implications regarding altered coronary microvascular regulation and the cause of coronary spasm after cardiac surgery.
Aspirin benefits patients with stroke but only just
Authors: Z. Kmietowicz
Journal: BMJ (1997)

Aspirin given soon after a stroke reduces deaths and disability by 1%–a modest but noteworthy effect–while heparin fails to offer any significant clinical advantage, according to the results of the international stroke trial.

The trial is the largest to look at the acute treatment of stroke ( Lancet 1997;349:1569-81). A total of 19 435 patients with suspected acute ischaemic stroke were randomly allocated aspirin (300 mg a day), heparin (5000 IU or 12500 IU twice a day), aspirin plus heparin, or no treatment within 48 hours of the start of symptoms; treatment was continued until discharge or for up to 14 days.

The results show …
Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
Authors: Marianne Abifadel, Mathilde Varret, Jean-Pierre Rabès, Delphine Allard, Khadija Ouguerram, Martine Devillers, Corinne Cruaud, Suzanne Benjannet, Louise Wickham, Danièle Erlich, Aurélie Derré, Ludovic Villéger, Michel Farnier, Isabel Beucler, Eric Bruckert, Jean Chambaz, Bernard Chanu, Jean-Michel Lecerf, Gerald Luc, Philippe Moulin, Jean Weissenbach, Annick Prat, Michel Krempf, Claudine Junien, Nabil G Seidah, Catherine Boileau
Journal: Nature Genetics (2003)