tbuckley/cabot-search huggingface dataset:
Respective Roles of Serological Status and Blood Specific Antihuman Herpesvirus 8 Antibody Levels in Human Herpesvirus 8 Intrafamilial Transmission in a Highly Endemic Area
Authors: Sabine Plancoulaine, Laurent Abel, David Trégouët, Renan Duprez, Monique van Beveren, Patricia Tortevoye, Alain Froment, Antoine Gessain
Journal: Cancer Research (2004)

Abstract Transmission of human herpesvirus 8 (HHV-8), the etiological agent of Kaposi’s sarcoma, occurs mainly during childhood in endemic countries and, to a large extent, through intrafamilial contacts. To additionally investigate this familial transmission, and especially the role of plasma anti-HHV–8 antibody titers, we conducted a large survey in a village from Cameroon, Central Africa, including 92 families (608 individuals). Plasma samples were tested for specific IgG directed against HHV-8 lytic antigens by immunofluorescence assay, and titers were determined by 2-fold dilutions. Global HHV-8 seroprevalence was 60%, raising from 32% under 9 years up to a plateau of around 62% between 15 and 40 years. The familial correlation patterns in HHV-8 seropositive/seronegative status showed strong dependence from mother to child and between siblings. In contrast, no familial correlation in anti-HHV–8 antibody levels was observed among infected subjects. In particular, no relationship was observed between the anti-HHV–8 antibody titer of HHV-8 seropositive mothers and the proportion of their HHV-8 seropositive children. Furthermore, a random permutation study of the anti-HHV–8 antibody titers among HHV-8 infected subjects showed that the main risk factor for infection was the HHV-8 serologic status and not the antibody level. In addition, no correlation was found between anti-HHV–8 antibody levels and buffy coat HHV-8 viral loads in a subsample of 95 infected subjects. Overall, these results strongly suggest that, in this highly endemic population from Central Africa, HHV-8 transmission mainly occurs from mother to child and between siblings, and it is independent of plasma antibody levels of HHV-8 infected relatives.
Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2011)

Abstract Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. Diagnosis: Diagnosis is based on bone marrow morphology. The presence of fibrosis, JAK2 / MPL mutation or +9/13q‐ cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. Risk stratification: The Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus) prognostic model for PMF can be applied at any point during the disease course and uses eight independent predictors of inferior survival: age &gt;65 years, hemoglobin &lt;10 g/dL, leukocytes &gt;25 × 10 9 /L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count &lt;100 × 10 9 /L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, ‐7/7q‐, i(17q), inv(3), ‐5/5q‐, 12p‐ or 11q23 rearrangement). The presence of 0, 1, “2 or 3,” and ≥4 adverse factors defines low, intermediate‐1, intermediate‐2, and high‐risk disease with median survivals of ∼ 15.4, 6.5, 2.9, and 1.3 years, respectively. A &gt;80% two‐year mortality is predicted by monosomal karyotype, inv(3)/i(17q) abnormalities, or any two of circulating blasts &gt;9%, leukocytes ≥40 × 10 9 /L or other unfavorable karyotype. Risk‐adapted therapy: Observation alone is adequate for asymptomatic low/intermediate‐1 risk disease. Allogeneic stem cell transplantation or experimental drug therapy is considered for intermediate‐2/ high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate‐1 risk disease. Splenectomy and low‐dose radiotherapy are used for drug‐refractory splenomegaly. Radiotherapy is also used for the treatment of non‐hepatosplenic EMH, PMF‐associated pulmonary hypertension, and extremity bone pain.
IGF-I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats
Authors: Luciano Sobrevals, Carlos Rodriguez, José Lorenzo Romero-Trevejo, Gabor Gondi, Iñaki Monreal, Astrid Pañeda, Nerea Juanarena, Sara Arcelus, Nerea Razquin, Laura Guembe, Gloria González-Aseguinolaza, Jesús Prieto, Puri Fortes
Journal: Hepatology (2009)

We investigated whether gene transfer of insulin-like growth factor I (IGF-I) to the hepatic tissue was able to improve liver histology and function in established liver cirrhosis. Rats with liver cirrhosis induced by carbon tetrachloride (CCl(4)) given orally for 8 weeks were injected through the hepatic artery with saline or with Simian virus 40 vectors encoding IGF-I (SVIGF-I), or luciferase (SVLuc). Animals were sacrificed 8 weeks after vector injection. In cirrhotic rats we observed that, whereas IGF-I was synthesized by hepatocytes, IGF-I receptor was predominantly expressed by nonparenchymal cells, mainly in fibrous septa surrounding hepatic nodules. Rats treated with SVIGF-I showed increased hepatic levels of IGF-I, improved liver function tests, and reduced fibrosis in association with diminished alpha-smooth muscle actin expression, up-regulation of matrix metalloproteases (MMPs) and decreased expression of the tissue inhibitors of MMPs TIM-1 and TIM-2. SVIGF-I therapy induced down-regulation of the profibrogenic molecules transforming growth factor beta (TGFbeta), amphiregulin, platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), and vascular endothelium growth factor (VEGF) and induction of the antifibrogenic and cytoprotective hepatocyte growth factor (HGF). Furthermore, SVIGF-I-treated animals showed decreased expression of Wilms tumor-1 (WT-1; a nuclear factor involved in hepatocyte dedifferentiation) and up-regulation of hepatocyte nuclear factor 4 alpha (HNF4alpha) (which stimulates hepatocellular differentiation). The therapeutic potential of SVIGF-I was also tested in rats with thioacetamide-induced liver cirrhosis. Also in this model, SVIGF-I improved liver function and reduced liver fibrosis in association with up-regulation of HGF and MMPs and down-regulation of tissue inhibitor of metalloproteinase 1 (TIMP-1).IGF-I gene transfer to cirrhotic livers induces MMPs and hepatoprotective factors leading to reversion of fibrosis and improvement of liver function. IGF-I gene therapy may be a useful alternative therapy for patients with advanced cirrhosis without timely access to liver transplantation.
Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector
Authors: D. Ostertag, K. K. Amundson, F. Lopez Espinoza, B. Martin, T. Buckley, A. P. G. da Silva, A. H. Lin, D. T. Valenta, O. D. Perez, C. E. Ibanez, C.-I. Chen, P. L. Pettersson, R. Burnett, V. Daublebsky, J. Hlavaty, W. Gunzburg, N. Kasahara, H. E. Gruber, D. J. Jolly, J. M. Robbins
Journal: Neuro-Oncology (2011)

Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized cytosine deaminase prodrug activating gene to the tumor lesion and leads to long-term survival after treatment with 5-fluorocytosine (5-FC). Survival benefit is dose dependent for both vector and 5-FC, and as few as 4 cycles of 5-FC dosing after Toca 511 therapy provides significant survival advantage. In the virally permissive CT26-BALB/c model, spread of Toca 511 to other tissues, particularly lymphoid tissues, is detectable by polymerase chain reaction (PCR) over a wide range of levels. In the Tu-2449-B6C3F1 model, Toca 511 PCR signal in nontumor tissues is much lower, spread is not always observed, and when observed, is mainly detected in lymphoid tissues at low levels. The difference in vector genome spread correlates with a more effective antiviral restriction element, APOBEC3, present in the B6C3F1 mice. Despite these differences, neither strain showed signs of treatment-related toxicity. These data support the concept that, in immunocompetent animals, a replicating retroviral vector carrying a prodrug activating gene (Toca 511) can spread through a tumor mass, leading to selective elimination of the tumor after prodrug administration, without local or systemic pathology. This concept is under investigation in an ongoing phase I/II clinical trial of Toca 511 in combination with 5-FC in patients with recurrent high-grade glioma (www.clinicaltrials.gov NCT01156584).
Long-Term Risk of Cardiovascular Disease in 5-Year Survivors of Testicular Cancer
Authors: Alexandra W. van den Belt-Dusebout, Janine Nuver, Ronald de Wit, Jourik A. Gietema, Wim W. ten Bokkel Huinink, Patrick T.R. Rodrigus, Erik C. Schimmel, Berthe M.P. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2006)

To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC).We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis.After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk.Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.
Significant lamotrigine overdose associated with acute pancreatitis
Authors: Benedict Nwogbe, Julia Ferié, Hannah Smith, Indunil Gunawardena, Ketan Dhatariya
Journal: Journal of the Royal Society of Medicine (2009)

In March 2007, a 24-year{old woman was admitted via the Emergency Department after an act of deliberate self{harm. Five hours prior to admission she had taken 4200 mg of lamotrigine. She denied taking any other medication at the time of this overdose. Her relevant medical history included two previous episodes of mixed overdoses (July 2002 and May 2006), depression and a psychotic episode for which she was treated with mirtazepine 30 mg once daily, lamotrigine 100 mg twice daily and risperidone 2 mg twice daily. At the time of admission she reported a regular intake of two 750 mL bottles of wine per evening, but had no previous history of alcohol{related liver or pancreatic problems. She had drunk two bottles of wine with her overdose. On admission, she was tachycardic, lethargic, dehydrated, showed slurred speech, with cerebellar signs of nystagmus and ataxia. She had no evidence of abdominal tenderness. Arterial blood gas measurements revealed a compensated metabolic acidosis. Full blood count, urea, electrolyte and liver function tests were normal. Her blood alcohol level was 100 mg/100 mL. Paracetamol and salicylate were not detected. A lamotrigine level was not taken because it is not routinely available in our institution. An electrocardiogram showed a sinus tachycardia only. Within 24 hours of admission she complained of upper abdominal pain and vomiting. Serum amylase was 1043 U/L (0–110 U/L). Liver transaminase, full blood count, calcium, glucose, urea and electrolyte levels were within reference ranges. The patient was diagnosed with acute pancreatitis, and at 48 hours achieved a Ranson score of 1 on assessment of severity, predicting a good prognosis, with less than 1% mortality. General supportive treatment was started with intravenous fluid resuscitation, analgesia and antiemetics. Abdominal ultrasound two days after onset of symptoms showed a thickened gall bladder wall, with some surrounding fluid and no evidence of gallstones. Her symptoms as well as amylase levels settled within three days and the patient was discharged five days after the initial overdose. An endoscopic ultrasound of the pancreas was performed six weeks after discharge. This showed a normal gallbladder and common bile duct. The pancreas had no features of chronic pancreatitis and had a normal calibre pancreatic duct. In the 12 months following discharge she was seen twice in the Emergency Department with symptoms and signs consistent with significant alcohol abuse, however on both occasions her amylase was normal.
An image-guided diagnostic pathway for undiagnosed pleural exudates
Authors: Coenraad Koegelenberg, Florian von Groote-Bidlingmaier, Johannes Bruwer, Enas Batubara, Chris Bolliger, Elvis Irusen, Andreas Diacon
Journal: European Respiratory Journal (2013)

Background: We assessed the efficiency and safety of an image-guided diagnostic pathway with ultrasound (US)-assisted closed pleural biopsy as an alternative to thoracoscopy as first-line investigation in undiagnosed pleural exudates.

Methods: Patients with non-diagnostic thoracocentesis were prospectively stratified on imaging as having (A) an associated mass lesion (>10mm) abutting the chest wall; (B) diffuse pleural thickening (>10mm) and/or nodularity or (C) insignificant/no pleural thickening. US-assisted repeat thoracocentesis and transthoracic fine-needle aspiration were performed on patients stratified to (A), and if non-diagnostic on on-site analysis, a Tru-Cut biopsy was performed in the same session. US-assisted thoracocentesis and Abrams needle biopsies were performed on all others aiming at the region(s) of interest (B) or low supra-diaphragmatic pleura (C). Thoracoscopy was reserved for cases not diagnosed by repeat thoracentesis and biopsy.

Results: Final diagnoses in 78 consecutive patients included malignancy (n=42), TB (n=30), and other causes (n=6). Accurate diagnoses were obtained in 69 (88.5%) with US-assisted thoracocentesis and biopsy. The yield was high for TB (93.3%) and malignancy (88.1%). Complications included mild haemoptysis (n=1) and pneumothorax (n=1, no intervention required). Thoracoscopy was performed in 13 cases (16.7%), including all 4 cases correctly diagnosed on closed biopsy as non-specific pleuritis, and yielded diagnoses in 12.

Conclusion: A diagnostic algorithm based on pleural morphology, US-assisted thoracocentesis and biopsy has a high diagnostic yield and offers an efficient and safe alternative to thoracoscopy as a first-line investigation in undiagnosed exudates.
The Speech of a Schizophrenic Child from Two to Six
Authors: THEODORE SHAPIRO, BARBARA FISH, GEORGE L. GINSBERG
Journal: American Journal of Psychiatry (1972)

The language development of a schizophrenic child was systematically observed from ages two to six. While the child attained increasing intelligibility and a normal score on a test of language development, finer analysis revealed a severe impairment of communicativeness. The changing relationship between the amounts of echoing and context disturbance in this child's noncommunicative speech indicates that speech can serve as a revealing index of pathology. His communicative speech was marked by rigidity and only limited use of tenses and transformations. The authors believe these rigidities are related to structural defects in integration and identification.
Baseline Allergic Co-morbidities and Aeroallergen Sensitivities in an Observational Study of Children with Moderate-to-Severe Inadequately Controlled Allergic Asthma - The BUS Study
Authors: K.D. Griscti, F. Kianifard, M. Figliomeni, N. Inhaber, M.A. Brown, C.A. Camargo, S.J. Szefler, R.K. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2010)
Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial
Authors: James W Denham, Allison Steigler, David S Lamb, David Joseph, Sandra Turner, John Matthews, Chris Atkinson, John North, David Christie, Nigel A Spry, Keen-Hun Tai, Chris Wynne, Catherine D'Este
Journal: The Lancet Oncology (2011)
Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples
Authors: Helena Bertilsson, May-Britt Tessem, Arnar Flatberg, Trond Viset, Ingrid Gribbestad, Anders Angelsen, Jostein Halgunset
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Low concentrations of citrate and high concentrations of choline-containing compounds (ChoCC) are metabolic characteristics observed by magnetic resonance spectroscopy of prostate cancer tissue. The objective was to investigate the gene expression changes underlying these metabolic aberrations to find regulatory genes with potential for targeted therapies. Experimental design: Fresh frozen samples (n = 133) from 41 patients undergoing radical prostatectomy were included. Histopathologic evaluation was carried out for each sample before a metabolic profile was obtained with high-resolution magic angle spinning (HR-MAS) spectroscopy. Following the HR-MAS, RNA was extracted from the same sample and quality controlled before carrying out microarray gene expression profiling. A partial least square statistical model was used to integrate the data sets to identify genes whose expression show significant covariance with citrate and ChoCC levels. Results: Samples were classified as benign, n = 35; cancer of low grade (Gleason score 6), n = 24; intermediate grade (Gleason score 7), n = 41; or high grade (Gleason score ≥8), n = 33. RNA quality was high with a mean RNA Integrity Number score of 9.1 (SD 1.2). Gene products predicting significantly a reduced citrate level were acetyl citrate lyase (ACLY, P = 0.003) and m-aconitase (ACON, P &amp;lt; 0.001). The two genes whose expression most closely accompanied the increase in ChoCC were those of phospholipase A2 group VII (PLA2G7, P &amp;lt; 0.001) and choline kinase α (CHKA, P = 0.002). Conclusions: By integrating histologic, transcriptomic, and metabolic data, our study has contributed to an expanded understanding of the mechanisms underlying aberrant citrate and ChoCC levels in prostate cancer. Clin Cancer Res; 18(12); 3261–9. ©2012 AACR.
Controlled Prospective Trial of Prednisolone and Cytotoxics in Progressive IgA Nephropathy
Authors: Francis W. Ballardie, Ian S. D. Roberts
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. In a single-center, multiple-referral source study, 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents, to therapy with low-dose cyclophosphamide then azathioprine, and to control groups. The follow-up period lasted 2 to 6 yr. Renal survival, as assessed by Kaplan-Meier analysis annually to 5 yr, showed significant preservation of function from 3 yr in the treatment group and 82, 82, 72, and 72% for 2, 3, 4, and 5 yr, respectively, compared with 68, 47, 26, and 6% in controls. Rate of loss of renal function, evaluated objectively by least-squares analyses of reciprocal serum creatinine, was reduced—and in one-third of the patients, arrested—during immunosuppressive treatment. Proteinuria, present in all patients at the time of entry into the trial, was reduced by treatment from 12 mo, compared with pretreatment levels or controls; erythrocyturia was reduced from 6 mo. Histologic activity and chronicity indexes were determined in renal biopsies performed at trial entry. Multivariate analysis demonstrated that mesangial cell proliferation and matrix scores were highest in those patients with more rapidly progressive disease. No morphologic variable or residual renal function predicted response to immunosuppressive therapy at entry. Mean arterial pressures did not differ significantly between treatment and control groups. There was thus no explanation other than treatment for the improved outcome in patients who received immunosuppressive therapy. Morbidity attributable to treatment or to renal failure occurred in both groups; an audit showed that benefits of therapy outweighed expected or minor side effects of drugs in this population at risk of end-stage renal failure. Patients selected for moderately progressive IgA nephropathy benefit from treatment with prednisolone and cytotoxic agents; results are consistent with modulation of systemic immune response or nephritic injury, thus explaining improved outcome, and indicate that this therapy has an acceptably low risk of side effects.
Eradicating war is essential to eliminate poverty and improve health
Authors: R. Stott
Journal: BMJ (2000)

EDITOR—We welcome the editorial on the International Poverty and Health Network and will encourage Medact to participate in the work of the network.1

Medact is an organisation of health professionals who are concerned about major threats to health, such as violent conflict, poverty, and environmental degradation. To the editorial's otherwise comprehensive list of objectives we would like to add one which we regard as vital:the elimination of war.

War and the preparation …
Francis Exton Crawley
Authors: Evalyn MacLeod
Journal: BMJ (2004)

Former consultant chest physician Liverpool (b Walney Island 1911; q Glasgow 1933; DPH, MD, FRCP), died from a stroke on 20 December 2003.

In 1947 he began his career as a consultant chest physician in Dorset. In 1950 he moved to Liverpool to begin his dream job as chief of a purpose built chest clinic, which he also administered. He was called the “flying doctor” because he ran round the hospital and clinic taking the stairs two at a time, leaving his staff puffing along behind him. In 1976 he retired to Ayr, where he indulged his love of horse racing as occasional race course doctor. Predeceased by his wife, Evalyn, he leaves three children and seven grandchildren.