tbuckley/cabot-search huggingface dataset:
Effect of granulocyte macrophage colony-stimulating factor in a patient with benign systemic mastocytosis.
Authors: T. Zuberbier, P. Welker, J. Grabbe, B.M. Henz
Journal: British Journal of Dermatology (2001)

We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM-CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult-onset systemic mastocytosis. In vitro effects of GM-CSF on bone marrow cultures before the start of treatment showed a marked inhibition of mast cell marker expression [tryptase, Kit, and high-affinity IgE receptor (FcepsilonRIalpha)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of GM-CSF for 10 weeks. After an initial improvement, increasing worsening of clinical symptoms was noted, and the patient refused further treatment. Lesional skin biopsies showed an increase of toluidine blue-positive mast cells, compared with uninvolved skin, with further significant increase after treatment. Similar results were obtained on staining for mast cell-specific tryptase and Kit, as well as for CD1a and FcepsilonRIalpha. These findings show that GM-CSF inhibits human bone marrow mast cell differentiation in vitro, and also in mastocytosis. However, GM-CSF apparently enhances recruitment of mast cell as well as dendritic cell precursors into the tissue during systemic treatment. These findings and the observed adverse clinical effects in the present patient make it unlikely that GM-CSF monotherapy will be beneficial for the treatment of mastocytosis.
SOME UNAPPRECIATED CAUSES OF ANEMIA IN CHILDHOOD.
Authors: W. C. HOLLOPETER
Journal: JAMA (1903)

The time was when the child's physician was called only to the acute troubles of childhood, the chronic sufferer drifted on, handicapped by a host of physical imperfections until an acute disorder would terminate the child's life. In many cases of milder specific diseases the child is left to fight its way back to health, scarcely reaching, unfortunately, its original vigor. <h3>DENTITION.</h3> Primary dentition, a physiologic process, is often a time of ill health and suffering to the child, but when this is complicated by the administration of improper food, irregularly given, which sooner or later disturbs the child's balance, we frequently find the little patient markedly anemic at the end of this period. For the last few years my attention has been constantly drawn to some of the unrecognized, or at least, unappreciated causes of anemia in growing children. We know the anemias of the acute diseases
Child Health Services Research
Authors: Christopher B. Forrest
Journal: JAMA (1997)

The characteristics of childhood as a unique developmental stage of life, the continuity of child health with adult health, and a distinctive child health care system justify a separate focus of health services research on children. Child health services research (CHSR) currently lacks the tools necessary to monitor the impact of health system change on children's health and health care and to compare the effectiveness of alternative treatment modalities. There is an urgent need to build the research capacity of this field of inquiry. Ignoring or minimizing attention to CHSR is both shortsighted and ultimately costly for families and the entire nation. We present arguments for why children merit a separate focus in health services research, identify factors that have led to the failure of appropriate development of CHSR, and offer a set of strategies for how to build the research capacity of the field.
Cardiac function in the normal newborn: additional information by computer analysis of the M-mode echocardiogram.
Authors: M G St John Sutton, D J Hagler, A J Tajik, E R Giuliani, J B Seward, D G Ritter, E L Ritman
Journal: Circulation (1978)

Computer analysis of the M-mode echocardiogram in 50 normal newborns provided measurements of wall thicknesses and chamber size and, in addition, assessment of right and left ventricular wall, septal, and cavity dynamics throughout the cardiac cycle. Data obtained with this new technique indicated that (1) right and left ventricular cavity functions are similar in the normal newborn, (2) right and left ventricular cavity filling and emptying vary directly with peak rates of septal and ventricular wall thinning and thickening, respectively, and (3) there is a close time relationship among maximum left atrial dimension, minimum left ventricular dimension, and mitral valve opening. This analysis, which is the first complete analysis of the echocardiogram in the newborn, provides a normal range of septal and ventricular wall dynamics as well as right and left ventricular and left atrial function and has clinical implications in that it may allow early recognition of both congenital and perinatal myocardial disease.
Comparison of breastfeeding rates in Scotland in 1990-1 and 1997-8
Authors: D. M Tappin
Journal: BMJ (2001)

distress is important.It is hard to explain this trend, especially in the case of deliveries without fetal distress, although we found a similar trend with assisted vaginal vertex deliveries for fetal distress. 4 The anxiety for the patient generated by the decision for caesarean section may provoke increased maternal catecholamine release that initially causes reduced perfusion of the placental bed and gas exchange, with temporary fetal acidosis.Cord pH values may not be a reliable assessment of fetal or neonatal wellbeing nor a good predictor of long term neurological outcome 5 but we question the benefit and wisdom of aiming to achieve delivery in all cases within 30 minutes.We thank Mrs Maggie Jefferies and the maternity records coding staff who provided a crosscheck to confirm complete collection of data.
P4-06-04: Detection of HER2 Gene Amplification in Circulating Tumor Cells and Disseminated Tumor Cells by Fluorescence In Situ Hybridization Using OncoCEE™.
Authors: S Krishnamurthy, FZ Bischoff, JA Mayer, K Wong, T Pham, HM Kuerer, AK Lodhi, A Bhattacharyya, CS Hall, A Lucci
Journal: Cancer Research (2011)

Abstract BACKGROUND: The status of HER2 gene amplification in circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) might provide useful information for monitoring response to trastuzumab therapy, and may provide a basis for consideration of trastuzumab in patients with HER2 negative primary tumors who have HER2 positive CTCs and/or DTCs. The majority of techniques utilized for detection of minimal residual disease are limited in their ability to allow detailed phenotypic and genotypic evaluation of the cells. We report the utility of a microfluidic platform (OncoCEE™,Biocept, San Diego) for detecting HER2 gene amplification in CTCs and DTCs in patients with non-metastatic breast cancer. METHODS: Peripheral blood (10ml) and bone marrow (BM) (1-2ml) were collected from patients with clinical stage I-III breast cancer in acid citrate dextrose solution (BD, Franklin Lakes, NJ) and anti-clumping reagent (OncoCEE-Sure™). Mononuclear cells were recovered using a Percoll density gradient method, incubated with a mixture of 10 primary capture antibodies (Abs), introduced into CEE™ microchannels, stained with fluorescent anti cytokeratin (CK) and CD45 abs and finally processed for fluorescence in situ hybridization (FISH) using probes specific to centromere 17 (spectrum green) and HER2 (spectrum arrange). The ratio of HER2:CEP17 &amp;gt;2.2 in any CK+/CD45- and CK-/CD45- cell was regarded as positive for HER2 gene amplification. RESULTS: Peripheral blood and/or BM from 78 patients (65 BM; 70 blood; 57 matched blood and BM) with T1NO (39), T1N1 (8), T2N0 (12), T2N1 (2), T2N2 (1), T2N3 (3), T3N0 (2), T3N1 (2), T3N2 (1), T4N0(5), T4N1 (3), with HER2+ (n=12) and HER2− (n=58) primary invasive breast tumors were studied. The 12 patients with HER2+ primary tumors had HER2+ DTCs in 3/12 (25%) and HER2+ CTCs in 1/9 (11%) cases respectively. HER2+ DTCs and HER2+ CTCs occurred in 12/55 (24%) and in 4/63 (6%) of the patients with HER2− primary breast tumors. HER2+ CTCs and DTCs occurred simultaneously in only 2 patients and in either blood (3) or BM (13) in the remaining patients. CONCLUSION: 1. The cell enrichment and extraction microfluidic technology (OncoCEE™) provides a sensitive platform for evaluation of HER2 gene amplification of CTCs and DTCs. 2. HER2+ primary tumors were associated with either HER2+ CTCs or DTCs in 25% of the patients. 3. HER2+ CTCs or DTCs occurred in 28% of patients with HER2−primary tumor. 4. Discordant HER2 status was contributed mainly by HER2+ DTCs occurring in HER2 - primary tumors. 5. The clinical significance of evaluating the status of HER2 gene amplification in CTCs and DTCs in the management of patients with breast cancer needs to be evaluated prospectively in larger clinical trials. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-06-04.
Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses
Authors: Susan E. Waltz, Laura Eaton, Kenya Toney-Earley, Karla A. Hess, Belinda E. Peace, Jeffrey R. Ihlendorf, Ming-Hai Wang, Klaus H. Kaestner, Sandra J.F. Degen
Journal: Journal of Clinical Investigation (2001)

Ron receptor activation induces numerous cellular responses in vitro, including proliferation, dissociation, and migration. Ron is thought to be involved in blood cell development in vivo, as well as in many aspects of the immune response including macrophage activation, antigen presentation, and nitric oxide regulation. In previous studies to determine the function of Ron in vivo, mice were generated with a targeted deletion of the extracellular and transmembrane regions of this gene. Mice homologous for this deletion appear to die early during embryonic development. To ascertain the in vivo function of Ron in more detail, we have generated mice with a germline ablation of the tyrosine kinase domain. Strikingly, our studies indicate that this domain of Ron, and therefore Ron cytoplasmic signaling, is not essential for embryonic development. While mice deficient in this domain are overtly normal, mice lacking Ron signaling have an altered ability to regulate nitric oxide levels and, in addition, have enhanced tissue damage following acute and cell-mediated inflammatory responses.
Frequency response of portable PEF meters.
Authors: J L Hankinson, M K Das
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Peak expiratory flow (PEF) is a dynamic parameter and therefore requires a measuring device with a high-frequency response. This study evaluated the frequency-response characteristics of eight commercially available PEF meters, using simulated forced-expiratory maneuvers with a computer-controlled mechanical pump. Three different PEF levels were used (200, 400, and 600 L/min) at six levels of harmonic-frequency content similar to those observed in human subjects. For waveforms with higher frequency content (at the high end or above the physiologic range), the Assess, Vitalograph, Pocket Peak, and Spir-O-Flow PEF meters all overread PEF (greater than 15% difference from target values) at all three PEF levels. These results suggest that the frequency response of PEF meters is an important consideration in the selection of such meters and should be included in device requirements. The current practice of using various levels of American Thoracic Society (ATS) waveform 24 with its low-frequency content may not adequately evaluate the frequency characteristics of PEF meters. An upper range (5% of the fundamental frequency) of 12 Hz, within the range observed in normal subjects, appears to be more practical than an upper limit of 20 Hz.
Nitrate tolerance in epicardial arteries or in the venous system is not reversed by N-acetylcysteine in vivo, but tolerance-independent interactions exist.
Authors: T Münzel, J Holtz, A Mülsch, D J Stewart, E Bassenge
Journal: Circulation (1989)

N-acetylcysteine is assumed to reverse nitrate tolerance by replenishing depleted intracellular sulfhydryl groups, but data on interactions of N-acetylcysteine and nitrates in patients with stable angina are controversial and disappointing. Therefore, we studied the effect of N-acetylcysteine on nitrate responsiveness of epicardial arteries and of the venous system (assessed as changes in effective vascular compliance) in dogs (n = 12) during long-term nitroglycerin treatment (1.5 micrograms/kg/min i.v. for 5-6 days). In dogs with nitroglycerin-specific tolerance (shift of venous or epicardial artery dilation to 15-17-fold higher dosages), N-acetylcysteine (100 mg/kg i.v.) had no dilator effect and did not alter the dose-response relations of nitroglycerin. Yet, in nontolerant dogs (n = 17), N-acetylcysteine augmented (1.5-2.0-fold) the dilation of epicardial arteries and the reduction of peripheral vascular resistance induced by 0.5-1.5 micrograms/kg/min nitroglycerin. In vitro, the augmentation of purified guanylate cyclase activity by nitroglycerin (10-100 microM) was potentiated by N-acetylcysteine (0.01-1.0 mM) in saline or in canine plasma, but N-acetylcysteine alone was ineffective. We conclude that 1) N-acetylcysteine does not restore nitroglycerin responsiveness in tolerant epicardial arteries or veins in vivo, 2) a small, tolerance-independent augmentation of nitroglycerin-induced dilation may result from N-acetylcysteine-induced extracellular formation of a stimulant of guanylate cyclase from nitroglycerin.
How much day surgery? Delphic predictions.
Authors: J. Gabbay, L. Francis
Journal: BMJ (1988)

A list was compiled of 83 of the commonest operations, which according to published reports may be performed on day patients but which in our district were usually performed on inpatients. The results of a national Delphi study among anaesthetists and general surgeons who were known to be in favour of day surgery produced estimates of the probable rates of day surgery for each of those operations under ideal conditions. Comparison of these figures with those from a Delphi study carried out in one district and with figures for day surgery carried out in that district and with waiting list figures enabled two health districts to focus their efforts to increase day surgery. The figures from the national Delphi study could be applied in other districts if the following are taken into account: Hospital Activity Analysis data must be validated; though there was consensus among the national Delphi consultants, personal clinical opinions varied; the case load may grow as waiting lists decrease.
Cytotoxic effects of antimicrobial photodynamic therapy on keratinocytes in vitro
Authors: B. Zeina, J. Greenman, D. Corry, W.M. Purcell
Journal: British Journal of Dermatology (2002)

Previous work has shown that cutaneous microbial species associated with skin conditions of microbial aetiology are susceptible to killing by photodynamic therapy (PDT) using visible light and methylene blue. Antimicrobial PDT (APDT) in vivo would require a therapeutic regimen where bacteria could be killed without damaging adjacent tissue.To study keratinocyte killing in vitro using APDT.We used a combination of methylene blue (100 microg mL(-1)) and visible light (42 mW cm(-2)), previously used for microbial killing, to study cytotoxic effects on keratinocytes. Kill rates and subsequent D-values were determined against a human keratinocyte cell line (H103) using trypan blue and neutral red dye viability tests.The kill rates for keratinocytes were exponential over the 90- and 180-min period of the experiment for neutral red and trypan blue, respectively. The corresponding D-values were shown to be 198 and 205 min using trypan blue exclusion and neutral red uptake viability tests, respectively.The kill rates for keratinocytes were 18-200-fold slower than those previously determined for cutaneous microbial species, suggesting that in vivo, APDT sufficient to reduce microbes by seven log cycles would have little cytotoxic effect on keratinocytes. This approach may offer a safe alternative to conventional antimicrobial treatment.
Risk of Serious Acute Neurological Illness After Immunization With Diphtheria-Tetanus-Pertussis Vaccine
Authors: James L. Gale
Journal: JAMA (1994)

To evaluate the association between serious acute neurological illness and receipt of whole-cell pertussis vaccine, given as diphtheria-tetanus-pertussis (DTP) vaccine.Population-based case-control study.Outpatient and inpatient hospital settings, physician practices, and the general population in Washington and Oregon states.A total of 424 confirmed cases of neurological illness were identified prospectively during a 12-month period by statewide active surveillance from the population of 218,000 children 1 to 24 months of age living in Washington and Oregon (estimated 368,000 DTP immunizations given). Each case child was matched to two population control children by birth date (+/- 5 days), gender, and county of birth. Written immunization records were used to determine whether illness occurred within 7 days of immunization in case children, or within 7 days of the same reference date in control children, thus qualifying as exposed.Outpatient and inpatient cases of complex febrile seizures, seizures without fever, infantile spasms, and acute encephalitis/encephalopathy confirmed by an expert panel masked to immunization history.The estimated odds ratio (OR) for onset of serious acute neurological illness within 7 days for young children exposed to DTP vaccine was 1.1 (95% confidence interval [CI], 0.6 to 2.0). When the analysis was restricted to children with encephalopathy or complicated seizures and adjusted for factors possibly affecting vaccine administration, the OR was 3.6 (95% CI, 0.8 to 15.2). Odds ratios for specific study diagnoses varied, but all CIs included 1. No elevated risk was observed for the largest group of illnesses studied, nonfebrile seizures (OR, 0.5; 95% CI, 0.2 to 1.5).This study did not find any statistically significant increased risk of onset of serious acute neurological illness in the 7 days after DTP vaccine exposure for young children.
Use of lithium and the risk of injurious motor vehicle crash in elderly adults: case-control study nested within a cohort
Authors: Mahyar Etminan, Brenda Hemmelgarn, J A C Delaney, Samy Suissa
Journal: BMJ (2004)

groups and adjust for clustering are likely to strengthen the findings presented here. ConclusionsAs expectations of continuing growth have evaporated in industrialised countries with the advent of the global economy, downsizing has become an increasingly important trend.This study indicates that downsizing may lead to elevated absence rates and increase cardiovascular mortality among people who remain employees.Policy makers, employers, and occupational health professionals should recognise that downsizing may pose a severe risk to health.
Smog and Anti-Smog — Iced Lollies — Christmas in the Wards
Authors: John Lister
Journal: New England Journal of Medicine (1953)

AS the first anniversary of the disastrous fog of last December appears, the smog consciousness of the nation seems to be reaching a climax. Even through the autumnal "season of mists and mellow fruitfulness," the patients with chronic bronchitis have been thronging their doctors' offices, acutely anxious lest pneumonia supervene, and now, almost daily, there are columns and news items in the national press on the subject of Smog and Anti-Smog. A boom in the sale of surgical gauze and chiffon scarves resulted from the advice of the local Medical Committee of the County of London that the public should . . .
Hepatic overexpression of caveolins increases bile salt secretion in mice
Authors: Mauricio Moreno, Hector Molina, Ludwig Amigo, Silvana Zanlungo, Marco Arrese, Attilio Rigotti, Juan Francisco Miquel
Journal: Hepatology (2003)

Caveolins are cholesterol–binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin–1 and caveolin–2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin–1 and caveolin–2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse–transcription polymerase chain reaction (RT–PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav–1– and Ad.Cav–2–infected mice exhibited a 10– and 7–fold increase in hepatic caveolin–1 and caveolin–2 protein expression, respectively. Caveolin–1–overexpressing mice had a significant increase in plasma high–density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin–1 and/or caveolin–2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin–1–overexpressing mice showed a 2.5–fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav–1 overexpression. No changes were seen in the protein mass of BS transporters Ntcp and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.
New Evidence for Stroke Prevention
Authors: Sharon E. Straus, Sumit R. Majumdar, Finlay A. McAlister
Journal: JAMA (2002)

ContextStroke is a major cause of morbidity and mortality, and the application of evidence for stroke prevention varies considerably.ObjectiveTo review the most recent, high-quality evidence for primary and secondary stroke prevention.Data Sources and Study SelectionSearches of MEDLINE, The Cochrane Library, and the ACP Journal Club were performed to identify English-language articles published from 1998 to 2001 that focused on primary and secondary stroke prevention. The references of each retrieved article were scanned, and experts in the field were contacted to identify additional relevant articles.Data ExtractionEach of the articles was appraised, and its quality was graded with levels of evidence based on specific scientific methods that affect a study's validity.Data SynthesisFor primary prevention of stroke, adequate blood pressure reduction, and treatment of hyperlipidemia, use of antithrombotic therapy in patients with atrial fibrillation and of antiplatelet therapy in patients with myocardial infarction are effective and supported by evidence from several randomized trials. Effective strategies for the secondary prevention of stroke include treatment of hypertension and hyperlipidemia, antithrombotic therapy for patients with atrial fibrillation, antiplatelet therapy, and carotid endarterectomy in patients with severe carotid artery stenosis.ConclusionsStroke is a major public health concern, and a significant body of evidence supports many primary and secondary prevention strategies.