tbuckley/cabot-search huggingface dataset:
Analgesia to painful stimuli in affective illness
Authors: G C Davis, M S Buchsbaum, W E Bunney
Journal: American Journal of Psychiatry (1979)

Patients with bipolar and unipolar affective illness (N = 76) were compared with 48 control subjects on a psychophysical pain rating procedure using both threshold and signal detection analysis. Affectively ill patients were more analgesic than controls, and depressed men were significantly more analgesic than depressed women or control subjects. Bipolar men showed a different pattern of analgesia than unipolar patients. Pain appreciation in depressed patients may be related to endogenous opiate-like substances; this could be assessed in narcotic antagonist studies of pain-tolerant depressed subjects.
Calcium-Channel Blockers for Hypertension — Uncertainty Continues
Authors: Jeffrey A. Cutler
Journal: New England Journal of Medicine (1998)

After the introduction of calcium-channel blockers into clinical practice nearly two decades ago, prescriptions for these drugs for the treatment of hypertension increased to the point where they became the most commonly prescribed antihypertensive drugs in the United States, at least as of a few years ago.1 Although calcium-channel blockers lower blood pressure and are well tolerated, until recently no data were available from randomized clinical trials regarding their effects on morbidity and mortality in patients with hypertension.In the Systolic Hypertension in Europe (Syst-Eur) trial,2 a long-acting member of the dihydropyridine subclass of calcium-channel blockers, nitrendipine, was found to . . .
Late Denervation in Patients with Antecedent Paralytic Poliomyelitis
Authors: Neil R. Cashman, Ricardo Maselli, Robert L. Wollmann, Raymond Roos, Roberta Simon, Jack P. Antel
Journal: New England Journal of Medicine (1987)

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls. The age at the time of acute poliomyelitis, severity of poliomyelitis, residual disability, number of years since acute poliomyelitis, and age at the time of study were comparable in the weakening and control groups. Evidence of remote denervation consistent with antecedent poliomyelitis was demonstrated in all patients by electromyography or muscle biopsy or both. In addition, active denervation (as evidenced by spontaneous activity on conventional electromyography, increased jitter on single-fiber electromyography, or atrophic myofibers) was found in 12 patients in the weakening group and in all 5 controls. Immunohistochemical detection of myofibers expressing the neural-cell adhesion molecule corroborated ongoing denervation in both patient groups. When muscle data from both groups were pooled, correlations were observed between the extent of past reinnervation and the degree of ongoing motor-unit instability. We conclude that the extensive reinnervation of denervated muscle that occurs in paralytic poliomyelitis may be followed by late denervation of the previously reinnervated muscle fibers. Electromyographic and muscle-biopsy evidence of ongoing denervation does not distinguish between stable patients with prior paralytic poliomyelitis and those with new weakness.
Clinical outcome of glioblastoma multiforme patients with long-term survival
Authors: H. Yoon, A. F. Hottinger, L. M. DeAngelis, A. B. Lassman, L. E. Abrey
Journal: Journal of Clinical Oncology (2007)

2069 Background: Glioblastoma multiforme (GBM) patients generally have a dismal prognosis with average survival of one year. Long-term survival of 3 years or more is rare and the clinical outcome of these patients has been poorly studied. Methods: Retrospective review of patients surviving 3 years or longer following diagnosis of GBM at our institution between 1985 and 2003. Clinical characteristics and long-term outcome were reviewed. Pathology was confirmed at our institution for all patients. Results: 39 long-term survivors of GBM were identified. Median age at diagnosis was 47 years (range: 14 - 69 years). Fifteen patients (pts) were older than 55 at time of diagnosis, and 5 were over 60. Presenting symptoms were headaches (56%), seizures (28%), hemiparesis (12%), aphasia (17%) or confusion (5%). Median KPS at diagnosis was 90 (range: 50–100). One patient (4%) underwent biopsy and X patients each (48%) underwent complete resection and incomplete resections. All patients received focal radiation therapy (RT) with a median dose of 5940 cGy (range: 4500 - 6120 cGy); 7 received concurrent temozolomide. Adjuvant chemotherapy in 35 pts consisted of temozolomide (54%), BCNU (38%), intra-arterial cisplatin (4%), or PCV (4%). Estimated median survival was 6.16 years (range: 3.1 - 18.2). After initial treatment, 11 pts had continuous clinical and radiographic remission, 28 relapsed, and 12 died. Median KPS at last follow-up was 70 (range 40 - 100). However, 19 pts (49%) developed delayed treatment-related complications at a median of 2.7 years (range: 1 -12 years) from initial diagnosis. Six (15%) developed RT necrosis (none of whom received concurrent temozolomide), 12 (31%) developed a subcortical dementia with associated leukoencephalopathy, and 9 (23%) developed strokes thought to be related to prior treatment. Conclusions: Long-term GBM survivors remain rare but occur in all age groups. These patients have a high risk of developing clinically significant long-term complications of their treatment. No significant financial relationships to disclose.
Ileal Mucosa in Familial Selective Vitamin B<sub>12</sub>Malabsorption
Authors: I. L. Mackenzie, R. M. Donaldson, J. S. Trier, V. I. Mathan
Journal: New England Journal of Medicine (1972)

Three brothers with selective vitamin B12 malabsorption and proteinuria were studied to characterize the absorptive defect in this disorder. Gastric juice from all three brothers contained adequate quantities of biologically active intrinsic factor. Serum concentrations of transcobalamin II were normal, and the patients had no demonstrable serum antibodies against intrinsic factor or against ileal receptors for intrinsic-factor-vitamin B12 complex (IF-B12). Mucosal biopsies from the terminal ileum of one brother were normal on light and electron microscopy. Intrinsic factor markedly stimulated uptake of cyanocobalamin by homogenates of these biopsies. Thus, selective vitamin B12 malabsorption is not associated with a morphologically identifiable lesion, and the absorptive defect does not seem to result from lack of ileal receptors for IF-B12. Rather, the defect appears at a stage of vitamin B12 absorption that occurs after IF-B12 attaches to the surface of the ileal cell and before the absorbed vitamin binds to transcobalamin II.
Chemotherapy Followed by Surgery Compared with Surgery Alone for Localized Esophageal Cancer
Authors: David P. Kelsen, Robert Ginsberg, Thomas F. Pajak, Daniel G. Sheahan, Leonard Gunderson, Joanne Mortimer, Norman Estes, Daniel G. Haller, Jaffer Ajani, Walter Kocha, Bruce D. Minsky, Jack A. Roth
Journal: New England Journal of Medicine (1998)

We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer.Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival.Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites.Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.
Biologic Differences between Neuroblastoma Stages IV-S and IV
Authors: Hie-Won L. Hann, Audrey E. Evans, Ian J. Cohen, John E. Leitmeyer
Journal: New England Journal of Medicine (1981)

In an examination of the biologic differences between neuroblastoma Stage IV-S (metastases to liver, skin, or bone marrow but not to bone), which has a high likelihood of spontaneous regression, and Stage IV (metastases to bone), which is usually fatal, 13 children with Stage IV-S disease and 17 with Stage IV were studied at diagnosis or shortly thereafter. Serum ferritin levels were elevated in 15 of the 17 children with Stage IV disease, but not in the 13 with Stage IV-S. E-rosette inhibitory factor was not present in the serum of 12 of 13 Stage IV-S patients, but was detected in 12 of 17 Stage IV patients. All 12 Stage IV patients with inhibitory factor had elevated serum ferritin levels. Elevated ferritin levels and E-rosette inhibitory factor appear to distinguish Stage IV neuroblastoma from Stage IV-S. (N Engl J Med. 1981; 305:425–9.)
Association of Coronary Stenosis and Plaque Morphology With Fractional Flow Reserve and Outcomes
Authors: Amir Ahmadi, Gregg W. Stone, Jonathon Leipsic, Patrick W. Serruys, Leslee Shaw, Harvey Hecht, Graham Wong, Bjarne Linde Nørgaard, Patrick T. O’Gara, Y. Chandrashekhar, Jagat Narula
Journal: JAMA Cardiology (2016)

Obstructive coronary lesions with reduced luminal dimensions may result in abnormal regional myocardial blood flow as assessed by stress-induced myocardial perfusion imaging or a significant fall in distal perfusion pressure with hyperemia-induced vasodilatation (fractional flow reserve [FFR] ≤0.80). An abnormal FFR has been demonstrated to identify high-risk lesions benefitting from percutaneous coronary intervention while safely allowing revascularization to be deferred in low-risk lesions, resulting in a decrease in the number of revascularization procedures as well as substantially reduced death and myocardial infarction. While FFR identifies hemodynamically significant lesions likely to produce ischemia-related symptoms, it remains less clear as to why it might predict the risk of acute coronary syndromes, which are usually due to plaque rupture and coronary thrombosis.Although the atherosclerotic plaques with large necrotic cores (independent of the degree of luminal stenosis) are known to be associated with vulnerability to rupture and acute coronary syndromes, emerging evidence also suggests that they may induce greater rates of ischemia and reduced FFR compared with non-lipid-rich plaques also independent of the degree of luminal narrowing. It is proposed that the presence of large necrotic cores within the neointima may be associated with the inability of the vessel to dilate and may predispose to ischemia and abnormal FFR.Having a normal FFR requires unimpaired vasoregulatory ability and significant luminal stenosis. Therefore, FFR should identify lesions that are unlikely to possess large necrotic core, rendering them safe for treatment with medical therapy alone. Further studies are warranted to determine whether revascularization decisions in patients with stable coronary artery disease could be improved by assessment of both plaque composition and ischemia.
Abstract P3-09-02: Early life residence, fish consumption and risk of breast cancer
Authors: A Haraldsdottir, JE Torfadottir, UA Valdimarsdottir, T Aspelund, L Tryggvadottir, LJ Launer, TB Harris, V Gudnason, L Steingrimsdottir
Journal: Cancer Research (2016)

Abstract Introduction: Few studies exist on the effect of diet during different periods of life, on breast cancer risk later in life. Great differences existed in food consumption between the capital and rural areas in Iceland in the middle of the 20th century, with very high fish consumption in coastal areas. Objectives: Our aim was to explore the effect of diet and residence during early life and midlife on breast cancer risk later in life. Methods and data: We used data from the Reykjavik Study, a population-based Icelandic cohort of 10049 women born between 1907 and 1935, and examined the association of residence in early life, used as a proxy for dietary habits, and risk of breast cancer. To further explore this association, we also used food frequency data at different periods of life, including adolescence, from the AGES-Reykjavik cohort, a subgroup of the Reykjavik Study, established in 2002. Participants provided information on residence in early life. By linkage with the Icelandic Cancer Registry, information on breast cancer diagnoses was available throughout 2013. Adjustments were made for a series of potential confounders, including residence for dietary analysis. Results: During a mean follow-up of 27.3 years, 744 women were diagnosed with breast cancer. We found a significant inverse association for breast cancer diagnosis among women who lived though the puberty period (20 years or more) in coastal villages compared with women residing in the capital area (HR = 0.74, 95% CI: 0.58, 0.94). In the subgroup analysis, we found that women with high fish consumption in midlife had lower risk of breast cancer in older age, compared with women with lower consumption, (OR = 0.60, 95% CI 0.38, 0,94). However, we did not observe a statistically significant association between high fish intake in adolescence and breast cancer (OR = 0.84, 95% CI 0.62 - 1.13). Conclusions: Our results suggest that high fish consumption in early- to midlife may be associated with reduced risk of breast cancer. Citation Format: Haraldsdottir A, Torfadottir JE, Valdimarsdottir UA, Aspelund T, Tryggvadottir L, Launer LJ, Harris TB, Gudnason V, Steingrimsdottir L. Early life residence, fish consumption and risk of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-09-02.
Asthma and bronchiectasis exacerbation
Authors: Bei Mao, Jia-Wei Yang, Hai-Wen Lu, Jin-Fu Xu
Journal: European Respiratory Journal (2016)

Bronchiectasis and asthma are common respiratory diseases worldwide. However, the influence of asthma on bronchiectasis remains unclear. The objective of this study is to analyse the effects of asthma on bronchiectasis exacerbation.Data from inpatients diagnosed with bronchiectasis with or without asthma at Shanghai Pulmonary Hospital (Shanghai, China) between January 2013 and December 2014 were retrospectively collected and analysed. 249 patients with only bronchiectasis and 214 patients with both bronchiectasis and asthma were included in the study. Follow-up records were used to evaluate the effect of asthma on bronchiectasis exacerbation.The variables found to be independently associated with bronchiectasis exacerbations were age (OR 1.07, 95% CI 1.03-1.11; p<0.001), duration of symptoms (OR 1.06, 95% CI 1.03-1.09; p<0.001), the presence of asthma (OR 2.6, 95% CI 1.15-5.88; p=0.021), forced expiratory volume in 1 s <50% predicted (OR 4.03, 95% CI 1.75-9.26; p=0.001), isolation of Pseudomonas aeruginosa in sputum (OR 2.41, 95% CI 1.00-5.79; p=0.05) and lung lesion extension to more than two lobes (OR 2.73, 95% CI 1.16-6.45; p=0.022).The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation.
Abnormal Iodoprotein in Nontoxic Goiter
Authors: Francis S. Greenspan, Jerold M. Lowenstein, Phyllis Spilker, Shirley Craig
Journal: New England Journal of Medicine (1963)

ABNORMAL iodoproteins have been found in the serum and thyroid glands of patients with various thyroid diseases: thyroiditis1 2 3; thyroid cancer4 , 5; exophthalmic goiter (Graves's disease)6; and occasionally nontoxic goiter.7 8 9 10 These iodoproteins are in general butanol insoluble and resemble albumin in their solubility and electrophoretic mobility. The production of large amounts of iodoprotein may contribute to the genesis of nontoxic goiter by diverting iodide into metabolically inactive material. In recent years several enzymatic defects in thyroid-hormone synthesis have been recognized as contributing to the development of nontoxic goiter: iodide-trapping defect; oxidase defect; deiodinase deficiency; coupling defect; and an abnormality . . .
Lack of Effect of Coumarin in Women with Lymphedema after Treatment for Breast Cancer
Authors: Charles L. Loprinzi, John W. Kugler, Jeff A. Sloan, Thom W. Rooke, Susan K. Quella, Paul Novotny, Rex B. Mowat, John C. Michalak, Philip J. Stella, Ralph Levitt, Loren K. Tschetter, Harold Windschitl
Journal: New England Journal of Medicine (1999)

Lymphedema of the arms can be a serious consequence of local and regional therapy in women with breast cancer. Coumarin has been reported to be effective for the treatment of women with lymphedema; we undertook a study in which we attempted to replicate those findings.
Vaccine-Associated Paralytic Poliomyelitis
Authors: Leonard Mermel, Diego Sanchez de Mora, Roland W. Sutter, Mark A. Pallansch
Journal: New England Journal of Medicine (1993)

To the Editor: Poliomyelitis was a major health problem in the United States until the introduction of inactivated poliovirus vaccine and attenuated oral poliovirus vaccine (OPV) in 1955 and 1961, respectively. Since 1963, trivalent OPV has been used routinely. Cases of vaccine-associated paralytic poliomyelitis have been described in recipients of this vaccine and contacts who were either immunodeficient or inadequately vaccinated1–4. We report a case of vaccine-associated paralytic poliomyelitis (the only 1 of 284 such cases reported to the Centers for Disease Control and Prevention [CDC] from 1961 through 1991) in an immunocompetent man who had received a . . .
Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination.
Authors: M. Noguchi, T. Mine, N. Komatsu, S. Suekane, F. Moriya, K. Yoshida, S. Yutani, S. Shichijo, A. Yamada, K. Itoh
Journal: Journal of Clinical Oncology (2010)

e13043 Background: To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination. Methods: Between October 2000 and October 2008, pre- and post- (sixth) vaccination peripheral blood lymphocytes and plasma from 500 advanced cancer patients under treatment with personalized peptide vaccination were analyzed for measurement of cytotoxic T lymphocyte (CTL) activity and IgG reactive to the vaccinated peptides, respectively. All 500 patients suffered from advanced cancer originating in the prostate (n = 174), colon and rectum (n = 74), pancreas (n = 50), stomach (n = 42), brain (n = 33), uterus (n = 28), lung (n = 22), kidney (n = 13), skin (n = 12), breast (n = 11), bladder and urinary tracts (n = 10), and elsewhere (n = 31).Correlations between overall survival and CTL or IgG response were investigated statistically. Results: The best clinical responses were for 43 PR, 144 SD, and 249 PD with a median overall survival of 9.9 months. Increased CTL or IgG response to at least one of the vaccinated peptides was observed in 199 of 332 (60%) or 187 of 300 (62%) patients tested, respectively. IgG response (P = 0.0015) was superior to CTL response (p = 0.167) with regard to correlation with overall survival. To statistically confirm the superiority of IgG response, the samples from advanced hormone-refractory prostate cancer patients (n = 20) who survived more than 900 days and those from those (n = 23) who died within 300 days were analyzed further. As a result, the number of peptides and the increase in IgG levels were found to be significantly higher in long-term survivors (p = 0.000282 and p = 0.00045, respectively). In contrast, those of CTL responses were not statistically different between the two groups. Conclusions: The measurement of IgG response was suggested as an immunological biomarker for prediction of the overall survival of advanced cancer patients under treatment with personalized peptide vaccination. No significant financial relationships to disclose.
Aflibercept (VEGF Trap) for advanced epithelial ovarian cancer (EOC) patients (pts) with symptomatic malignant ascites: Preliminary results of a pilot study
Authors: N. Colombo, G. Mangili, S. Mammoliti, M. Kalling, B. Tholander, L. Sternas, G. Buzenet, D. Chamberlain
Journal: Journal of Clinical Oncology (2008)

14598 Background: Aflibercept, has demonstrated the ability to reduce formation of ascites in preclinical models of EOC, as well as in advanced EOC patients. Aflibercept, a potent angiogenesis inhibitor fusion protein, is comprised of portions of human vascular endothelial growth factor VEGF receptor R1+R2 (Flt-1, KDR) extracellular domains and fused to the Fc-portion of human IgG. Aflibercept binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. Methods: Aflibercept, 4 mg/kg, i.v. was administered every 2 weeks, in pts with advanced EOC and symptomatic ascites requiring frequent paracentesis (pct). Eligibility criteria included resistance to prior platinum based therapy and topotecan and/or liposomal doxorubicin, ECOG performance status of 0–2, normal organ function, no proteinuria (<500 mg/24 hrs or UPCR<1), controlled blood pressure, an average of <30 days between baseline pct. prior to study entry. Primary endpoint is Repeat Paracentesis Response Rate (RPRR), defined as at least a doubling of time to the first pct compared to a baseline average. Results: 12 out of 15 pts have been treated, until December 15, 2007. Pts received 1–13 cycles of aflibercept. Time to first pct. was 12–205 days. 8/10 evaluable pts. achieved a RPRR response as per protocol. Pts. had received 2–9 lines of prior chemotherapy. Adverse events included, grade 3–4 (% per entry): bowel obstruction (40%) nausea, vomiting (30%), anorexia, edema, general health deterioration (20%) and 1 case of bowel perforation. Reasons for discontinuation were either progressive disease, clinical bowel obstruction or clinical deterioration. Conclusion: Aflibercept has shown activity in prolonging the time to repeat paracentesis in this setting. A randomized placebo controlled trial is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis Regeneron, sanofi-aventis sanofi-aventis