tbuckley/cabot-search huggingface dataset:
Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: The past decade and where we are heading
Authors: Victor A. Levin
Journal: Neuro-Oncology (1999)

Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging, neurosurgery, neuroanesthesia, radiotherapy, and chemotherapy for CNS tumors. Unfortunately, our progress has not yet met our expectations. Because of the infiltrative nature of most primary brain tumors, neurosurgery can never be expected to be curative for the majority of gliomas. Because infiltrative tumors interdigitate with normal brain cells and are not highly sensitive to irradiation, one cannot expect radiotherapy to be curative without serious damage to normal brain cells. The hope for a cure, then, rests with chemotherapy. Those who administer chemotherapy to patients with CNS tumors fully expect that, in time, long-term survival and, ultimately, the cure will become an everyday reality. To achieve that reality, however, new treatment concepts and drugs are needed.
Risk of Intussusception after Monovalent Rotavirus Vaccination
Authors: Eric S. Weintraub, James Baggs, Jonathan Duffy, Claudia Vellozzi, Edward A. Belongia, Stephanie Irving, Nicola P. Klein, Jason M. Glanz, Steven J. Jacobsen, Allison Naleway, Lisa A. Jackson, Frank DeStefano
Journal: New England Journal of Medicine (2014)

Although current rotavirus vaccines were not associated with an increased risk of intussusception in large trials before licensure, recent postlicensure data from international settings suggest the possibility of a small increase in risk of intussusception after monovalent rotavirus vaccination. We examined this risk in a population in the United States.Participants were infants between the ages of 4 and 34 weeks who were enrolled in six integrated health care organizations in the Vaccine Safety Datalink (VSD) project. We reviewed medical records and visits for intussusception within 7 days after monovalent rotavirus vaccination from April 2008 through March 2013. Using sequential analyses, we then compared the risk of intussusception among children receiving monovalent rotavirus vaccine with historical background rates. We further compared the risk after monovalent rotavirus vaccination with the risk in a concurrent cohort of infants who received the pentavalent rotavirus vaccine.During the study period, 207,955 doses of monovalent rotavirus vaccine (including 115,908 first doses and 92,047 second doses) were administered in the VSD population. We identified 6 cases of intussusception within 7 days after the administration of either dose of vaccine. For the two doses combined, the expected number of intussusception cases was 0.72, resulting in a significant relative risk of 8.4. For the pentavalent rotavirus vaccine, 1,301,810 doses were administered during the study period, with 8 observed intussusception cases (7.11 expected), for a nonsignificant relative risk of 1.1. The relative risk of chart-confirmed intussusception within 7 days after monovalent rotavirus vaccination, as compared with the risk after pentavalent rotavirus vaccination, was 9.4 (95% confidence interval, 1.4 to 103.8). The attributable risk of intussusception after the administration of two doses of monovalent rotavirus vaccine was estimated to be 5.3 per 100,000 infants vaccinated.In this prospective postlicensure study of more than 200,000 doses of monovalent rotavirus vaccine, we observed a significant increase in the rate of intussusception after vaccination, a risk that must be weighed against the benefits of preventing rotavirus-associated illness. (Funded by the Centers for Disease Control and Prevention.).
Abstract 1372: A cell based high throughput screening assay for inhibitors of melanoma with high S100B
Authors: Paul T. Wilder, Kira Gianni, Deborah L. Green, David J. Weber
Journal: Cancer Research (2011)

Abstract The calcium regulated S100B protein is over-expressed in many cancers including malignant melanoma where high levels of S100B correlate inversely with patient survival. It has been shown that increased S100B is not only a marker for cancer but may promote tumor survival by directly affecting the activity of several cell signaling proteins. For example, S100B has been shown to bind wild-type p53 in a calcium-dependent manner, sequestering it, and resulting in the loss of p53-dependent tumor suppression activities, and transient knockdown of S100B with siRNA has been shown to reverse this affect in melanoma cell lines. Therefore, the discovery of compounds that specifically inhibit the growth of melanoma cells with high levels of S100B may provide a useful therapeutic strategy. We have developed a cell based high throughput screening assay where the effect of small compounds on the growth of MALME-3M and WM115 melanoma cells with a stable shRNA to knockdown S100B is compared to the isogenically matched cell control containing a stably expressing a scrambled shRNA. Out of the greater than 15,000 compounds screened many inhibited growth of the melanoma cells, some had selectivity inhibiting the growth of the S100B high cells, and inversely high S100B was found to overcome the growth inhibition caused by several compounds. Previously, many S100B inhibitors found using an in vitro screening assay were found to function by chemically modifying Cys84 in S100B, so S100B might act as a sink to sequester some of the cysteine reactive compounds protecting cells from these compounds in some cases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1372. doi:10.1158/1538-7445.AM2011-1372
Antidepressant Medications in Children
Authors: Benedetto Vitiello, Susan Swedo
Journal: New England Journal of Medicine (2004)

In June 2003, the Medicine and Healthcare Products Regulatory Agency of the British Department of Health warned physicians to avoid the off-label use of paroxetine, a selective serotonin-reuptake inhibitor (SSRI) antidepressant, for the treatment of depression in children (18 years of age or younger). This action was taken in response to concern about a possible association between SSRIs and suicidal behavior, which includes a broad range of symptoms ranging from fleeting thoughts of self-harm to attempted suicide. Proprietary data examined by the United Kingdom regulatory agency showed a slight increase in suicidal behavior among patients who were randomly assigned to . . .
Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries.
Authors: C G Brilla, J S Janicki, K T Weber
Journal: Circulation Research (1991)

Left ventricular hypertrophy (LVH) in rats with genetic hypertension is accompanied by abnormal myocardial diastolic stiffness and impaired coronary reserve. Whether these functional defects are related to a structural remodeling of the myocardium that includes an interstitial and perivascular fibrosis, myocyte hypertrophy, and medial thickening of intramyocardial coronary arteries is uncertain. To address these issues, 14-week-old male spontaneously hypertensive rats with established hypertension and LVH were treated with low-dose (SLO group: 2.5 mg/kg/day, n = 11) or high-dose (SHI group: 20 mg/kg/day, n = 9) oral lisinopril for 12 weeks to sustain hypertension and LVH or to normalize arterial pressure and myocardial mass, respectively. When SHI and SLO groups were compared with age- and sex-matched 26-week-old untreated spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto rats (n = 9), we found 1) normalization of blood pressure (p less than 0.005) and complete regression of LVH (p less than 0.005) in the SHI group and no significant blood pressure or LVH reduction in the SLO group, 2) complete regression of morphometrically determined myocardial interstitial and perivascular fibrosis in SHI and SLO groups (p less than 0.025) associated with normalization of diastolic stiffness, measured in the isolated heart (p less than 0.025), and 3) regression of medial wall thickening of intramyocardial coronary arteries only in the SHI group (P less than 0.005), accompanied by a normalization of coronary vasodilator reserve to adenosine (p less than 0.005). Thus, interstitial fibrosis and not LVH is responsible for abnormal myocardial diastolic stiffness, whereas medical wall thickening of intramyocardial resistance vessels, influenced by arterial pressure, is associated with impaired coronary reserve.
Photochemistry of tetrachlorosalicylanilide and its relevance to the persistent light reactor
Authors: A.K. DAVIES, N.S. HILAL, J.F. McKELLAR, G.O. PHILLIPS
Journal: British Journal of Dermatology (1975)

The photochemistry of 3,5,3',4'-tetrachlorosalicylanilide has been studied in solution under carefully controlled conditions. When irradiated in a buffered solution of pH 7.4 (physiological pH), three atoms of chlorine are liberated from the molecule instead of one as suggested by earlier photochemical work. From this observation a mechanism is proposed to explain the long-term photobiological effect of this compound in skin i.e. that of the persistent light reactor.
Scotland's new chief medical officer welcomes reforms of training
Authors: D C Carter
Journal: BMJ (1996)

Table 1-Result of Medline search for "case-control studies," "questionnaires," and "family practice" 1992-6 MeSH heading No of citations 1 Case-control studies 9172 2 Questionnaires 14 786 3 Family practice 6863 1+3 21 2+3 548questionnaire studies to case-control studies was 1.6:1, whereas for family practice the ratio was 26:1.The time has come to redress the balance and move on from placing too much emphasis on questionnaire surveys as a quantitative method of research in general pracitice.
Permethrin 5% dermal cream: A new treatment far scabies
Authors: Professor David Taplin, Terri Lynn Meinking, Sherri L. Porcelain, Pedro M. Castillero, Joaquin Antonio Chen
Journal: Journal of the American Academy of Dermatology (1986)

Permethrin 5% dermal cream (Burroughs Wellcome Co.) was compared in an investigator-blinded, randomized study against lindane 1% lotion (Kwell) for the treatment of microscopically confirmed scabies. Eleven of twenty-three patients treated with permethrin cream were cured in 2 weeks (48%). Only two patients had scabies 1 month following a single treatment with this product, giving a cure rate of 91%. One of these two patients was considered to have a reinfestation. Only three of twenty-three (13%) patients treated with 1% lindane lotion (Kwell) were free of scabies 2 weeks after a single treatment and fifteen of twenty-three (65%) were cured at 1 month. The unusually high percentage of treatment failures (35%) following lindane therapy may have been related to extensive use of this agent for head lice and scabies in this village during the preceding 5 years, The higher cure rate at 1 month seen with permethrin cream was significant (p < 0.025). Permethrin 5% dermal cream offers a new, cosmetically elegant alternative to lindane therapy and was effective in a community in which lindane demonstrated an unacceptable level of treatment failures. Permethrin 5% dermal cream (Burroughs Wellcome Co.) was compared in an investigator-blinded, randomized study against lindane 1% lotion (Kwell) for the treatment of microscopically confirmed scabies. Eleven of twenty-three patients treated with permethrin cream were cured in 2 weeks (48%). Only two patients had scabies 1 month following a single treatment with this product, giving a cure rate of 91%. One of these two patients was considered to have a reinfestation. Only three of twenty-three (13%) patients treated with 1% lindane lotion (Kwell) were free of scabies 2 weeks after a single treatment and fifteen of twenty-three (65%) were cured at 1 month. The unusually high percentage of treatment failures (35%) following lindane therapy may have been related to extensive use of this agent for head lice and scabies in this village during the preceding 5 years, The higher cure rate at 1 month seen with permethrin cream was significant (p < 0.025). Permethrin 5% dermal cream offers a new, cosmetically elegant alternative to lindane therapy and was effective in a community in which lindane demonstrated an unacceptable level of treatment failures.
Paralytic Disease Associated With Oral Polio Vaccines
Authors: Donald A. Henderson, John J. Witte, Leo Morris, Alexander D. Langmuir
Journal: JAMA (1964)

SINCE 1961 when the oral poliomyelitis vaccines were first made available for general use in the United States, scattered cases of paralytic disease have occurred in association with these vaccines. Many of the cases have been clinically indistinguishable from poliomyelitis. Epidemiologically, the pattern of their occurrence has raised the possibility that some may have been caused by the vaccine. In 1962 when the existence of this problem was first appreciated, the Surgeon General of the Public Health Service convened a special advisory committee which met on a number of occasions between August and December. The Committee reviewed in detail reported cases of paralytic disease occurring within a period of 30 days following ingestion of the oral poliomyelitis vaccines. The Committee concluded that 18 cases of paralytic poliomyelitis were "compatible with the possibility of having been induced by the vaccine." Of these, 11 followed type III vaccine and 7 followed type
Total Absence of Eosinophils in a Patient with an Allergic Disorder
Authors: WILLIAM FRANKLIN
Journal: Annals of Internal Medicine (1981)

A 45-year-old woman with a 25-year history of episodic urticaria and rhinitis had no detectable eosinophils in blood or bone marrow; levels of other leukocytes were normal. No eosinophils were found in the nasal discharge or the exudate elicited in skin windows by ragweed extract, to which the patient exhibited an immediate-type hypersensitivity response. A complement-dependent IgG-related activity in the patient's serum cytotoxically degranulated human eosinophils in vitro without affecting neutrophils. Antieosinophil activity was confirmed by the ability of a single dose of the patient's serum to suppress significantly the eosinophil counts in monkeys for up to 12 hours. This is the first description of an isolated absence of eosinophils, a condition that may present with allergic manifestations.
MPs crticise plans for restructuring research council institutes
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

Research council institutes (RCIs) should not automatically become embedded within universities or other higher education organisations, as has been suggested by some observers, a report by MPs says. Instead, their structure and location needs to be decided on a case by case basis according to how they can best contribute to future scientific research, the House of Commons' science and technology committee concludes.

In March 2006 the committee announced an inquiry into the institutes after “a school of thought that RCIs are no longer the most effective way of conducting basic research.”

The United Kingdom has eight research councils. They have a total annual budget of £2.8bn (€4.1bn; $5.5bn) for 2007-8 to fund research and training in their own research centres and in universities; some 130 centres; and units collectively known as research council institutes.

In its report, the committee highlights comments by …
Hormone Replacement Therapy in Relation to Breast Cancer
Authors: Chi-Ling Chen
Journal: JAMA (2002)

Studies of long-term hormone replacement therapy (HRT) suggest an associated increased risk of breast cancer, but whether this association differs according to histologic type of cancer has not been extensively studied.To determine whether the association between HRT and risk of breast cancer varies by HRT formulation and differs across histologic cancer types.Nested case-control study among 705 postmenopausal women enrolled in the Group Health Cooperative of Puget Sound (GHC) who were aged 50 to 74 years and had primary invasive breast cancer diagnosed between July 1, 1990, and December 31, 1995 (cases), and 692 randomly selected aged-matched female members of GHC (controls).Incidence and type of breast cancer by duration of HRT use in the 5-year period ending 1 year before diagnosis, which was ascertained from computerized pharmacy records.The incidence of breast cancer, all histologic types combined, was increased by 60% to 85% in recent long-term users of HRT, whether estrogen alone or estrogen plus progestin. Longer use of HRT (odds ratio [OR], 3.07 for 57 months or more; 95% confidence interval [CI], 1.55-6.06) and current use of combination therapy (OR, 3.91; 95% CI, 2.05-7.44) were associated with increased risk of lobular breast cancer. Long-term HRT use was associated with a 50% increase in nonlobular cancer (OR, 1.52 for 57 months or more; 95% CI, 1.01-2.29).Our data add to the growing body of evidence that recent long-term use of HRT is associated with an increased risk of breast cancer and that such use may be related particularly to lobular tumors.
Altered platelet function in cirrhosis of the liver: Impairment of inositol lipid and arachidonic acid metabolism in response to agonists
Authors: Giacomo Laffi, Fabio Cominelli, Marco Ruggiero, Sandra Fedi, Vincenzo P. Chiarugi, Giorgio La Villa, Massimo Pinzani, Paolo Gentilini
Journal: Hepatology (1988)

Hemorrhagic disorders are common in patients with liver cirrhosis and result from several factors including impaired platelet function. We evaluated platelet aggregation and arachidonic acid metabolism in response to standard agonists in platelet-rich plasma from 12 cirrhotic patients with mild impairment of liver function (Child A), 12 patients with severe liver dysfunction (Child B and C) and 12 healthy subjects. Platelet aggregation and thromboxane A2 production were consistently reduced in patients with severe liver impairment. To determine whether the platelet dysfunction is due to an intrinsic platelet defect or a circulating inhibitor, we measured platelet aggregation and thromboxane A2 synthesis on washed platelets in healthy subjects and in Child B and C patients. The aggregating response of washed platelets in response to thrombin, collagen and arachidonic acid was markedly reduced, suggesting an intrinsic platelet defect. The biochemical events underlying platelet aggregation were investigated by prelabeling platelets with [1-14C]arachidonie acid. Thrombin-induced activation of phospholipase C (measured as the release of [1-14C]phosphatidic acid) and phospholipase A2 (measured as the release of [1-14C]arachidonic acid and its metabolites) was greatly impaired in platelets from patients with severe liver impairment. We conclude that in advanced cirrhosis there is a severe reduction in platelet aggregatory response to physiologic agonists due to an intrinsic platelet defect which is related to an impairment of the platelet transmembrane signaling mechanism induced by receptor stimulation.
The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretion in Man
Authors: Jens F. Rehfeld, Flemming Stadil
Journal: Journal of Clinical Investigation (1973)

The effect of gastrin on basal- and glucose-stimulated insulin secretion was studied in 32 normal, young subjects. The concentration of gastrin and insulin in serum was measured radioimmunochemically. Maximal physiologic limit for the concentration of gastrin in serum was of the order of 160 pmol per liter as observed during a protein-rich meal. Oral ingestion of 50 g glucose produced a small gastrin response from 28+/-3 to 39+/-5 pmol per liter (mean +/-SEM, P < 0.01). Intravenous injection or prolonged infusion of gastrin increased the concentration of insulin in peripheral venous blood to a maximum within 2 min followed by a decline to basal levels after a further 10 min. The minimum dose required to induce a significant insulin response (31.2 ng gastrin per kg) increased the gastrin level in serum above the physiologic range. Maximum effect was obtained with 500 ng gastrin per kg. When 15.6 ng (7.1 pmol) gastrin per kg body weight and 25 g glucose were injected simultaneously, the glucose-induced insulin response was potentiated (from 2.32+/-0.33 to 4.33+/-0.98 nmol per liter per 20 min, P < 0.02), even though gastrin concentrations only increased to 71.2+/-6.6 pmol per liter. No effect, however, was noted on glucose disposal. 15.6 ng gastrin per kg given i.v. 30 min before an i.v. glucose tolerance test was without significant effect on the insulin response. The results indicate that gastrin can stimulate a rapid and short-lived release of insulin. In physiologic concentrations gastrin potentiates the glucose-stimulated insulin secretion and is without effect on basal insulin secretion. A small release of gastrin during oral glucose ingestion may to a limited extent contribute to the nonglycemic insulin secretion. During protein ingestion, gastrin probably stimulates insulin secretion significantly.
Pulmonary Mycobacterium kansasii infection: comparison of radiological appearances with pulmonary tuberculosis.
Authors: A. J. Evans, A. J. Crisp, R. B. Hubbard, A. Colville, S. A. Evans, I. D. Johnston
Journal: Thorax (1996)

BACKGROUND: A study was undertaken to determine if there are differences in the radiological appearances at presentation between pulmonary infections caused by Mycobacterium kansasii and Mycobacterium tuberculosis. Correct recognition of the organism has important implications with regard to initial therapy and contact tracing. METHODS: The initial chest radiographs of 28 patients with pulmonary M kansasii infection were compared with those of 56 age, sex, and race matched patients with M tuberculosis infection. All patients in both groups were culture positive and none was known to be HIV positive. The radiographs were analysed independently by two radiologists who were unaware of the causative organism. RESULTS: Radiographic abnormalities in patients with M kansasii infection were more frequently unilateral and right side predominant, while those with tuberculosis more frequently involved a lower lobe. Air space shadowing involving more than one bronchopulmonary segment and pleural effusions were seen less frequently in M kansasii infection (four of 28 (14%) versus 30 of 56 (54%) and none of 28 versus 15 of 56 (27%)). Cavitation (21 of 28 (75%) versus 34 of 56 (61%) was seen to a similar extent in patients with M kansasii infection and in those with tuberculosis. Cavities tended to be smaller in patients with M kansasii infection (p &lt; 0.01). CONCLUSIONS: Differences are seen in the radiographic appearances of pulmonary infection caused by M kansasii and M tuberculosis. These differences are not sufficient to allow a positive diagnosis on the basis of radiographic findings alone, but the presence of a pleural effusion or lower lobe involvement makes M kansasii infection very unlikely.