tbuckley/cabot-search huggingface dataset:
Mitral Valve Prolapse Prevalence and Complications
Authors: Martin St John Sutton, Arthur E. Weyman
Journal: Circulation (2002)

itral valve prolapse (MVP) is generally understood to be the systolic displacement of an abnormally thickened, redundant mitral leaflet into the left atrium during systole. 1 This valvular abnormality has been associated with mid-systolic clicks, late systolic murmurs, and serious complications such as bacterial endocarditis, severe mitral regurgitation, and sudden death. 2 Unfortunately, our understanding of the prevalence, complication rate, and associations of mitral valve prolapse has been clouded by the use of varying techniques, changing diagnostic criteria, and conclusions drawn from highly selected referral populations.Despite this confusion, an understanding of the prevalence of mitral valve prolapse and the identification of subgroups most susceptible to complications remain important because MVP is the most common cause of valve repair/replacement for isolated mitral regurgitation in the United States, 3 and the thickened leaflets form a recognized substrate for bacterial endocarditis.
Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal
Authors: Jens H. Henriksen, Jens Juul Holst, Søren Møller, Kim Brinch, Flemming Bendtsen
Journal: Hepatology (1999)

Leptin is a cytokine peptide that decreases appetite and thereby food intake and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate hepatic cells. Because a change in circulating leptin in cirrhosis could be caused by an altered production rate, altered disposal rate, or both, the present study was undertaken to identify regions of leptin overflow into the blood stream and regions of leptin extraction. Patients with alcoholic cirrhosis (n = 16) and control patients without liver disease (n = 12) were studied during catheterization with elective blood sampling from different vascular beds. Blood samples for leptin determination (radioimmunoassay) were taken simultaneously from artery/hepatic vein, artery/renal vein, artery/iliac vein, and artery/cubital vein. Patients with cirrhosis had significantly increased circulating leptin (7.3 vs. control 2.6 ng/mL, P &lt; .002) that correlated directly to ascitic–free body mass index ( r = 0.71, P &lt; .005). A significant renal extraction ratio of leptin was observed in control patients (0.16) and in patients with cirrhosis (0.07), but the latter value was significantly lower than in the control patients (-44%, P &lt; .05) and inversely correlated to serum creatinine ( r = -0.60, P &lt; .05). A significant, but equal, hepatosplanchnic extraction of leptin was observed in cirrhotic patients and control patients (0.08 vs. 0.07). In patients with cirrhosis a significant cubital venous–arterial difference in leptin was observed, but not in control patients. The iliac venous/arterial leptin ratio was significantly above 1.0 in both groups and of similar size (1.16 vs. 1.15), but a higher difference in concentration was found in the cirrhotic patients (+33%, P &lt; .05). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno–arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis is most likely caused by a combination of decreased renal extraction and increased release from subcutaneous abdominal, femoral, gluteal, retroperitoneal pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed drained through hepatic veins could not be identified as a source of increased circulating leptin in cirrhosis, but a contribution by the portosystemic collateral flow cannot be excluded.
THE PLACENTA AND PROTEIN METABOLISM
Authors: G. H. Whipple, R. B. Hill, R. Terry, F. V. Lucas, C. L. Yuile
Journal: The Journal of Experimental Medicine (1955)

Plasma proteins tagged in vivo by feeding D-L-lysine-ϵ-C14 to donor dogs have been administered to pregnant dogs by both oral and intravenous routes. A relatively small percentage of the C14 activity originally incorporated in these proteins is found to pass from mother to fetus after intravenous injection. The amount transferred tends to increase with the length of gestation period and total number of fetuses. Plasma protein labeled with I131 does not cross the placenta in the dog, but does in the rabbit. Evans blue dye does not cross the placenta of the dog. After oral administration of labeled plasma protein or lysine, C14 is transferred promptly and in considerable quantity to the fetus. Labeled plasma proteins disappear more rapidly from the circulation of pregnant than of normal dogs. This increased metabolic turnover occurs without excretion of any excess waste metabolites. The chorionic epithelium, gram for gram, is probably 2 to 3 times as active as the hepatic epithelium in protein metabolism. These findings indicate an important placental function related to maternal and fetal protein metabolism. While the placenta utilizes maternal plasma proteins and amino acids, in a quantitative sense the latter appear to supply the major nitrogen needs of the growing fetus.
Malignant Melanoma Arising in the Setting of Epidermolysis Bullosa Simplex
Authors: Thomas L. Hocker, Matthew C. Fox, Jeffrey H. Kozlow, Joseph V. Gonzalez, Tor A. Shwayder, Lori Lowe, May P. Chan
Journal: JAMA Dermatology (2013)

Patients with epidermolysis bullosa (EB) do not carry a significantly increased risk of melanoma but are prone to developing large, markedly atypical melanocytic nevi (EB nevi), which may mimic melanoma clinically and histologically. Many authors now favor a conservative approach in managing atypical pigmented lesions in patients with EB.We present the case of a 30-year-old woman with severe EB simplex who sought care for a large red and black ulcerated plaque. The clinical differential diagnosis included EB nevus and melanoma. An incisional punch biopsy specimen revealed an atypical melanocytic proliferation with focal florid pagetoid spread and involving elongated rete ridges, consistent with invasive acral lentiginous melanoma. The subsequent amputation was confirmatory. Micrometastasis was detected in 1 of 5 sentinel lymph nodes.To our knowledge, this is the first reported case of melanoma arising in EB simplex-affected skin. It highlights the difficulty in differentiating melanoma from an EB nevus. Despite the increasing awareness of EB nevi, a high index of suspicion for melanoma should be maintained, and early biopsy is recommended when evaluating large pigmented lesions in patients with EB.
Alterations in calcium handling in cardiac hypertrophy and heart failure
Authors: C Balke
Journal: Cardiovascular Research (1998)

There is conflicting data concerning the effects of cardiac hypertrophy and failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+ transients, and the characteristics of Ca2+ sparks. These discrepancies are probably due to multiple factors. First, the effects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by which cardiac hypertrophy and heart failure are generated (genetic alteration, pressure overload, volume overload, high rate pacing, etc.) influence the results obtained. Second, with many animal models and diseased human hearts, the disease process is not uniformly distributed throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and SR function clearly depend on the extent of disease expression. Myocardial contractility increases with cardiac hypertrophy whereas it decreases with heart failure. Thus, it is difficult to compare results from different models of hypertrophy and heart failure at different stages of disease. More consistent data is likely to be obtained from longitudinal studies using a single animal model of disease. The challenge before us is to develop animal models that mimic human disease, which can be studied longitudinally during the progression of the disease process. This approach coupled with continued improvement in Ca2+ imaging and a greater understanding of normal E-C coupling, will enable us to identify precisely the abnormalities in E-C coupling that occur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities.
Listeria monocytogenes meningitis and decreased phagocytosis associated with iron overload.
Authors: B S van Asbeck, H A Verbrugh, B A van Oost, J J Marx, H W Imhof, J Verhoef
Journal: BMJ (1982)

A patient with Listeria monocytogenes meningitis was found to have idiopathic haemochromatosis and monocytes with reduced phagocytic capacity. The phagocytic function recovered completely after a series of therapeutic phlebotomies. In-vitro iron had a deleterious effect on the phagocytic capacity of monocytes and granulocytes. These findings show that iron overload in the host can increase susceptibility to L monocytogenes infection not only by increasing the virulence of the organism but also by reducing the phagocytic capacity of the monocytes.
A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.
Authors: S S Fojo, P Lohse, C Parrott, G Baggio, C Gabelli, F Thomas, J Hoffman, H B Brewer
Journal: Journal of Clinical Investigation (1989)

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.
Post-Traumatic Aneurysm of the Left Ventricle
Authors: DUNCAN A. KILLEN, WALTER G. GOBBEL, RICHARD FRANCE, VERNON A. VIX
Journal: Circulation (1969)

Three cases of left ventricular aneurysm secondary to external violence are reported. Each patient presented with a pseudoaneurysm of the left ventricle, following penetrating trauma in two instances and blunt trauma in the third instance. The interval between injury and diagnosis ranged from 5 months to 24 years. Two patients underwent successful resection of the aneurysm. Repair was not attempted in the third patient. Only 16 cases of post-traumatic left ventricular aneurysm have previously been reported. In 13 of the 19 cases available for review, the trauma was blunt and in six penetrating. The aneurysm could be determined to be a true aneurysm in five instances and a false aneurysm in eight instances. Complications (rupture, cardiac failure, embolism, and arrhythmia) proved fatal in eight cases. Each of the eight patients subjected to aneurysmectomy survived.
Prospective Study to Assess Short-Term Intra-Articular and Tenosynovial Changes in the Aromatase Inhibitor–Associated Arthralgia Syndrome
Authors: Leilani Morales, Steven Pans, Kilian Verschueren, Ben Van Calster, Robert Paridaens, Rene Westhovens, Dirk Timmerman, Luc De Smet, Ignace Vergote, Marie-Rose Christiaens, Patrick Neven
Journal: Journal of Clinical Oncology (2008)

Purpose Arthralgia is an adverse class effect of aromatase inhibitors (AIs). To date, its exact mechanism remains unclear. The purpose of this study was to investigate the changes in clinical rheumatologic features and magnetic resonance imaging (MRI) of hands and wrists in AI and tamoxifen users. Patients and Methods This is a prospective single-center study including 17 consecutive postmenopausal patients with early breast cancer receiving either tamoxifen (n = 5) or an AI (n = 12). At baseline and after 6 months, patients filled in a rheumatologic history questionnaire and a rheumatologic examination including a grip strength test was done. At the same time points, MRI of both hands and wrists was performed. The primary end point was tenosynovial changes from baseline on MRI. Secondary end points were changes from baseline for morning stiffness, grip strength, and intra-articular fluid on MRI. Wilcoxon signed ranks was used to test changes from baseline and the Spearman correlation coefficient to assess the association between rheumatologic and MRI changes from baseline. Results At 6 months, patients on AI had a decrease in grip strength (P = .0049) and an increase in tenosynovial changes (P = .0010). The decrease in grip strength correlated well with the tenosynovial changes on MRI (P = .0074). Only minor changes were seen in patients on tamoxifen. AI users reported worsening of morning stiffness and showed an increase in intra-articular fluid on MRI. Conclusion The functional impairment of hands in the AI-associated arthralgia syndrome is characterized by tenosynovial changes on MRI correlating with a significant decrease in hand grip strength.
Disorder-Specific Dissociation of Orbitofrontal Dysfunction in Boys With Pure Conduct Disorder During Reward and Ventrolateral Prefrontal Dysfunction in Boys With Pure ADHD During Sustained Attention
Authors: Katya Rubia, Anna B. Smith, Rozmin Halari, Fumie Matsukura, Majeed Mohammad, Eric Taylor, Michael J. Brammer
Journal: American Journal of Psychiatry (2008)

Objective: Among children, attention deficit hyperactivity disorder (ADHD) and conduct disorder are often comorbid and overlap clinically. Neuropsychological evidence suggests that children with conduct disorder demonstrate more prominent motivational problems and children with ADHD demonstrate more prominent attention deficits relative to healthy comparison subjects. The purpose of the present study was to investigate disorder-specific abnormalities in the neurobiological correlates of motivation and sustained attention in children and adolescents with pure conduct disorder and children and adolescents with pure ADHD. Method: Participants were male pediatric patients, ages 9–16 years, with noncomorbid conduct disorder (N=14) and noncomorbid ADHD, combined hyperactive-inattentive subtype (N=18), as well as age- and IQ-matched healthy comparison subjects (N=16). Both patient groups were medication naive. Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation during a rewarded continuous performance task that measured sustained attention as well as the effects of reward on performance. Results: During the sustained attention condition, patients with noncomorbid ADHD showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex and increased activation in the cerebellum relative to patients with noncomorbid conduct disorder and healthy comparison subjects. Patients with noncomorbid conduct disorder showed decreased activation in paralimbic regions of the insula, hippocampus, and anterior cingulate as well as the cerebellum relative to patients with noncomorbid ADHD and healthy comparison subjects. However, during the reward condition, patients with noncomorbid conduct disorder showed disorder-specific underactivation in the right orbitofrontal cortex, while patients with noncomorbid ADHD showed disorder-specific dysfunction in the posterior cingulate gyrus. Conclusions: The findings revealed a process-related dissociation of prefrontal dysfunction in ADHD and conduct disorder patients. Attention-related dysfunction in the ventrolateral prefrontal cortex was seen in ADHD patients, and reward-related dysfunction in the orbitofrontal cortex was seen in conduct disorder patients. These findings, together with the pattern of paralimbic dysfunction demonstrated among children with conduct disorder during sustained attention, support theories of abnormalities in orbitofrontal-paralimbic motivation networks in individuals with conduct disorder and, in contrast, ventrolateral fronto-cerebellar attention network dysfunction in individuals with ADHD.
Progressive Right Ventricular Dysfunction in Patients With Pulmonary Arterial Hypertension Responding to Therapy
Authors: Mariëlle C. van de Veerdonk, Taco Kind, J. Tim Marcus, Gert-Jan Mauritz, Martijn W. Heymans, Harm-Jan Bogaard, Anco Boonstra, Koen M.J. Marques, Nico Westerhof, Anton Vonk-Noordegraaf
Journal: Journal of the American College of Cardiology (2011)
Molecular Dependence of Estrogen Receptor–Negative Breast Cancer on a Notch-Survivin Signaling Axis
Authors: Connie W. Lee, Christopher M. Raskett, Igor Prudovsky, Dario C. Altieri
Journal: Cancer Research (2008)

Abstract Despite progress in the management of breast cancer, the molecular underpinnings of clinically aggressive subtypes of the disease are not well-understood. Here, we show that activation of Notch developmental signaling in estrogen receptor (ER)–negative breast cancer cells results in direct transcriptional up-regulation of the apoptosis inhibitor and cell cycle regulator survivin. This response is associated with increased expression of survivin at mitosis, enhanced cell proliferation, and heightened viability at cell division. Conversely, targeting Notch signaling with a peptidyl γ-secretase inhibitor suppressed survivin levels, induced apoptosis, abolished colony formation in soft agar, and inhibited localized and metastatic tumor growth in mice, without organ or systemic toxicity. In contrast, ER+ breast cancer cells, or various normal cell types, were insensitive to Notch stimulation. Therefore, ER− breast cancer cells become dependent on Notch-survivin signaling for their maintenance, in vivo. Therapeutic targeting of this pathway may be explored for individualized treatment of patients with clinically aggressive, ER− breast cancer. [Cancer Res 2008;68(13):5273–81]
Marijuana and Benzodiazepines in Patients Receiving Methadone Treatment
Authors: Robert L. DuPont
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Much of the criticism of methadone treatment has centered on the use of an addicting drug to treat drug addiction. One of the seldom appreciated advantages of methadone treatment is the leverage methadone treatment staff have in eliminating nonmedical drug use by requiring nonuse as a condition of either take-home doses or continuation in the treatment program. Compliance with this condition is achieved by drug testing, now required by the Food and Drug Administration for all methadone programs.<sup>1</sup> Concern about drug use by methadone recipients led to drug screening for heroin, barbiturates, cocaine, and other stimulants. Worry about alcohol abuse by methadone patients led to testing for alcohol use in many programs. However, marijuana and benzodiazepines, both highly abusable drugs, appear to receive little attention in methadone programs. Although there has been some recent concern about the abuse of benzodiazepines by patients receiving methadone maintenance,<sup>2</sup>
Effects of cyclosporin at various concentrations on dexamethasone intracellular uptake in multidrug resistant cells
Authors: J F Maillefert
Journal: Annals of the Rheumatic Diseases (2000)

The multidrug resistance phenomenon results from the expression of P-glycoprotein (P-gp), a drug-efflux pump. Corticosteroids are substrates for P-gp, whose function can be inhibited by cyclosporin. This study evaluates the ability of cyclosporin to modulate dexamethasone uptake in multidrug resistant cells.The K 562 cell line, which does not express P-gp and a P-gp expressing clone, K562/ADM, were used. Cells were incubated with H3-dexamethasone in the absence or presence of cyclosporin at various concentrations. Then, cells were washed, lysed, and radioactivity was measured.The uptake of dexamethasone alone was higher in sensitive than in resistant cells. Addition of cyclosporin induced a dose dependent increase of dexamethasone uptake in resistant cells, whereas the drug did not influence dexamethasone uptake in parental cells.Cyclosporin, at therapeutic concentrations induces a moderate, but significant increase in dexamethasone accumulation in multidrug resistant cells. Thus, cyclosporin might increase the intestinal absorption of corticosteroids or their accumulation in mononuclear cells, or both, thereby increasing their therapeutic efficacy.
COSTS OF TRANSRADIAL AND TRANSFEMORAL PCI AT FIVE U.S. HOSPITALS
Authors: Amit P. Amin, John House, David Safley, Adnan Chhatriwalla, Helmut Giersiefen, Andreas Bremer, Martial Hamon, Dmitri Baklanov, Yele Aluko, David Wohns, David Mathias, Robert Applegate, David Cohen, Steven P. Marso
Journal: Journal of the American College of Cardiology (2013)
Interferonlike factors from antigen- and mitogen-stimulated human leukocytes with antirickettsial and cytolytic actions on Rickettsia prowazekii. Infected human endothelial cells, fibroblasts, and macrophages.
Authors: C L Wisseman, A Waddell
Journal: The Journal of Experimental Medicine (1983)

Unique features of the primary site of rickettsial replication in typhus fevers, i.e., within the endothelial cells of small blood vessels in tissues, suggest that effector mechanisms, other than those dependent on phagocytosis by activated macrophages with enhanced microbicidal properties, most likely are necessary to explain the cell-mediated immune control of intracellular rickettsial replication in these sites. Theoretically, such mechanisms might involve contact between infected endothelial cells and activated T lymphocyte subpopulations or macrophages or immunologically induced soluble factors or lymphokines. Support for the existence of at least one of these alternative effector mechanisms is presented here for Rickettsia prowazekii. Cultures of human blood leukocytes, upon immunologically specific stimulation with R. prowazekii antigen or nonspecific stimulation with the mitogen phytohemagglutinin, produce soluble factor(s) in the supernatant fluid which, in culture, have (a) an intracellular antirickettsial action on R. prowazekii-infected human endothelial cells, fibroblasts, and macrophages, and (b) a specific cytolytic action on R. prowazekii-infected, but not uninfected bystander, human fibroblasts. Neither action is demonstrable in R. prowazekii-infected chicken embryo fibroblasts. The factor(s) has no direct antimicrobial action on extracellular rickettsiae and is inactivated by heating at 56 degree C for 1 h or by acid treatment at pH 2. Expression of the antirickettsial action requires new host cell messenger transcription and protein synthesis, whereas the cytolytic action does not. The circumstances of production and action and the properties of the factor(s) responsible for the intracellular antirickettsial, and perhaps also the cytolytic action are consistent with those of immune interferon (IFN-gamma).