tbuckley/cabot-search huggingface dataset:
The Interaction of Histamine with Gastrin and Carbamylcholine on Oxygen Uptake by Isolated Mammalian Parietal Cells
Authors: Andrew H. Soll
Journal: Journal of Clinical Investigation (1978)

Using oxygen uptake as an index of the physiological response of isolated parietal cells, the interactions between histamine and gastrin and between histamine and carbamylcholine and the effects of atropine and metiamide on these interactions have been studied. Parietal cells were isolated from canine fundic mucosa by sequential exposure of separated mucosa to collagenase and EDTA. In previous studies carbamylcholine, isobutyl methyl xanthine, gastrin, and histamine have each been shown to increase oxygen uptake by these cells. Isobutyl methyl xanthine greatly enhanced the histamine effect. Carbamylcholine was inhibited by atropine but not by metiamide, histamine was inhibited by metiamide but not by atropine, and gastrin was inhibited by neither, suggesting that each of these agents has a direct action on the parietal cell. In the present studies, potentiating interactions between histamine and carbamylcholine and between histamine and gastrin have been demonstrated. Against a histamine (0.1 and 1 μM) plus isobutyl methyl xanthine (0.1 mM) background, the dose for 50% response for gastrin was approximately 1 nM, and the maximal response was obtained at 0.1 μM. When added to these combinations of stimulants, metiamide and atropine retained their respective specificities against stimulation by histamine and carbamylcholine, in that responses were inhibited to the level that was seen when the component of the pair that was not inhibited was given alone.
Outcomes of Allergy to Insect Stings in Children, with and without Venom Immunotherapy
Authors: David B.K. Golden, Anne Kagey-Sobotka, Philip S. Norman, Robert G. Hamilton, Lawrence M. Lichtenstein
Journal: New England Journal of Medicine (2004)

Children are thought to "outgrow" the allergy to insect stings, but there are no reports documenting the natural history of this reaction. We studied the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated.Between 1978 and 1985, we diagnosed allergic reaction to insect stings in 1033 children, of whom 356 received venom immunotherapy. We conducted a survey of these patients by telephone and mail between January 1997 and January 2000, to determine the outcome of stings that occurred in the period from 1987 through 1999.Of the 1033 patients, 512 patients (50 percent) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and an incidence of stings of 43 percent. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients, or 3 percent) than in untreated patients (19 of 111 patients, or 17 percent; P=0.007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients, or 32 percent) than if they had received venom immunotherapy (2 of 43 patients, or 5 percent; P=0.007). In patients who had been treated and who had a history of mild (cutaneous) systemic reaction (i.e., one with only cutaneous manifestations), none of the 21 subjects who received stings had a systemic reaction.A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults.
Molecular Biomarkers in Advanced Renal Cell Carcinoma
Authors: Pablo Maroto, Brian Rini
Journal: Clinical Cancer Research (2014)

The availability of agents directly targeting tumorigenic and angiogenic pathways has significantly improved the outcomes of patients with advanced renal cell carcinoma (RCC) in recent years. However, all patients eventually become resistant and a substantial percentage experience immediate disease progression with first-line targeted therapy. In addition, patients have variable clinical benefit and/or tolerance to different agents, including drugs within the same class. Thus, the choice of therapy for an individual patient remains empiric at present. Upon this landscape, several molecular biomarkers have been investigated with the purpose of guiding therapy. This review discusses prognostic biomarkers correlating with the outcome of patients independent of therapy, and predictive biomarkers of treatment response, including circulating biomarkers (such as VEGF and VEGF-related proteins, cytokine and angiogenic factors, and lactate dehydrogenase), and tissue-based biomarkers (such as single-nucleotide polymorphisms). Many potential prognostic and predictive molecular biomarkers have now been identified in RCC, although none has yet entered into clinical practice, and all require prospective validation in appropriately designed randomized studies. In the near future, however, validated biomarkers may become integral to management strategies in RCC, enabling tailored treatment for individual patients to improve clinical outcomes.
Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell Leukemia
Authors: Robert J. Kreitman, Maryalice Stetler-Stevenson, Inger Margulies, Pierre Noel, David J.P. FitzGerald, Wyndham H. Wilson, Ira Pastan
Journal: Journal of Clinical Oncology (2009)

Purpose To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL. Patients and Methods Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts. Patients were stratified into three groups: response to cladribine less than 1 year, those with a response lasting 1 to 4 years, or no response and uncontrolled infection. Patients received BL22 40 μg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils ≥ 1,500/mm 3 , hemoglobin ≥ 11 g/dL, and platelets ≥ 100,000/mm 3 , were observed. Patients without HR were re-treated at 30 μg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1. Results Thirty-six patients were enrolled including 26, nine, and one in groups 1 to 3. The response after one cycle (CR, 25%; PR, 25%) improved when 56% were re-treated (CR, 47%; PR, 25%). CR rate was similar in groups 1 and 2 (P = .7). Twenty-two with baseline spleen height lower than 200 mm had higher CR (64% v 21%; P = .019) and OR rates (95% v 36%; P = .0002) compared to 14 with spleens either absent or higher than 200 mm. The only serious toxicity was reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in two patients (6%). High neutralizing antibodies were observed in four patients (11%) and prevented re-treatment. Conclusion BL22 activity in HCL is confirmed. Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy.
Targeted Biallelic Inactivation of <i>Pten</i> in the Mouse Prostate Leads to Prostate Cancer Accompanied by Increased Epithelial Cell Proliferation but not by Reduced Apoptosis
Authors: Xiaoqian Ma, Angelique C. Ziel-van der Made, Binha Autar, Hetty A. van der Korput, Marcel Vermeij, Petra van Duijn, Kitty B. Cleutjens, Ronald de Krijger, Paul Krimpenfort, Anton Berns, Theo H. van der Kwast, Jan Trapman
Journal: Cancer Research (2005)

Abstract The PTEN tumor suppressor gene is frequently inactivated in human tumors, including prostate cancer. Based on the Cre/loxP system, we generated a novel mouse prostate cancer model by targeted inactivation of the Pten gene. In this model, Cre recombinase was expressed under the control of the prostate-specific antigen (PSA) promoter. Conditional biallelic and monoallelic Pten knock-out mice were viable and Pten recombination was prostate-specific. Mouse cohorts were systematically characterized at 4 to 5, 7 to 9, and 10 to 14 months. A slightly increased proliferation rate of epithelial cells was observed in all prostate lobes of monoallelic Pten knock-out mice (PSA-Cre;Pten-loxP/+), but minimal pathologic changes were detected. All homozygous knock-out mice (PSA-Cre;Pten-loxP/loxP) showed an increased size of the luminal epithelial cells, large areas of hyperplasia, focal prostate intraepithelial neoplasia lesions and an increased prostate weight at 4 to 5 months. More extensive prostate intraepithelial neoplasia and focal microinvasion occurred at 7 to 9 months; invasive prostate carcinoma was detected in all male PSA-Cre;Pten-loxP/loxP mice at 10 to 14 months. At 15 to 16 months, a rare lymph node metastasis was found. In hyperplastic cells and in tumor cells, the expression of phospho-AKT was up-regulated. In hyperplastic and tumor cells, expression of luminal epithelial cell cytokeratins was up-regulated; tumor cells were negative for basal epithelial cell cytokeratins. Androgen receptor expression remained detectable at all stages of tumor development. The up-regulation of phospho-AKT correlated with an increased proliferation rate of the epithelial cells, but not with a reduced apoptosis.
Unexplained dyspnoea in a patient with idiopathic myelofibrosis
Authors: Praveen Pissay Gopala Rao, Rachel Buxton-Thomas, Brendan Tinwell, Adrian Draper, Johnny Vlahos, Simon L F Walsh
Journal: Thorax (2012)

A 41-year-old with idiopathic myelofibrosis was referred to the chest clinic with a 1-month history of progressive dyspnoea and intermittent wheeze. There was no history of haemoptysis and the patient was a lifelong non-smoker. On examination, the patient was afebrile, cachectic and had hepatosplenomegaly. Haemoglobin was 6.0 g/dl, white cell count 3.6×109/l, platelet count 98×109/l. Blood smear showed marked anisopoikilocytes, prominent tear drop cells and polychromasia. Bone marrow aspirate was hypercellular, showed reduction in the degree of maturation, and a marked decrease in the proportion of erythroid cells. There was no evidence of acute leukaemia or metastatic malignancy. Microbiologic analysis of the sputum and blood for pulmonary infection was negative. Lung function test showed a restrictive …
Study throws doubt on protective effects of HRT for heart disease
Authors: Scott Gottlieb
Journal: BMJ (2000)

The effectiveness of hormone replacement therapy in treating heart disease in postmenopausal women remained in question as contradictory studies were presented at a major cardiology conference in California.

Researchers from Wake Forrest University Baptist Medical Center in North Carolina presented findings at the American College of Cardiology's 49th annual scientific sessions in Anaheim, California, showing that neither oestrogen alone nor oestrogen combined with progestogen slowed the advances of heart disease in postmenopausal women or significantly lowered cholesterol concentrations.

Known as the ERA study (the estrogen replacement and arteriosclerosis trial), …
Inflammatory markers and cardiovascular health in older adults
Authors: S KRITCHEVSKY, M CESARI, M PAHOR
Journal: Cardiovascular Research (2005)

In the past decade inflammatory markers have emerged as strong independent risk indicators for cardiovascular disease. Even though adults over the age of 65 experience a high proportion of such events, most epidemiologic data are from middle-aged populations. In this review we examine the role that inflammatory markers play in the prediction of incident cardiovascular disease specifically in older adults. In studies of adults < 65 years, IL-6, TNFalpha and IL-10 levels have been shown to predict cardiovascular outcomes. The data on C-reactive protein are inconsistent, but CRP levels appear to be less useful in old-age than in middle-age. Fibrinogen levels predict mortality but in a non-specific manner. In the elderly inflammatory markers are non-specific measures of health and predict both disability and mortality even in the absence of clinical cardiovascular disease. Thus it is possible that, in older age-groups, interventions designed to prevent cardiovascular disease through the modulation of inflammation would also be helpful in reducing disability and mortality.
Exercise is associated with improved asthma control in adults
Authors: S. Dogra, J.L. Kuk, J. Baker, V. Jamnik
Journal: European Respiratory Journal (2010)

Global asthma control levels are suboptimal. The influence of regular exercise on asthma control is unclear. We assessed the effects of a 12-week supervised exercise intervention followed by 12 weeks of self-administered exercise on adults with partially controlled asthma (n = 21) and matched controls (n = 15). Assessments were conducted at baseline and week 12 for both the exercise and control group, and again at week 24 for the exercise group. There was a significant treatment effect on asthma control in the exercise group, as measured by the Asthma Control Questionnaire (ACQ), from baseline to week 12, compared with the control group. A clinically significant improvement (0.5 increase in ACQ score) was observed for asthma quality of life and ACQ in the exercise group from baseline to week 12. There was a significant improvement in aerobic fitness from baseline to week 24 in the exercise group. In conclusion, a 12-week supervised exercise intervention led to improvements in asthma control and quality of life in partially controlled asthmatics motivated to exercise. These improvements were maintained, while aerobic fitness and perceived asthma control significantly improved over an additional 12 weeks of self-administered exercise. These findings indicate that a structured exercise intervention can improve asthma control.
Physician Reports of Terminal Sedation without Hydration or Nutrition for Patients Nearing Death in the Netherlands
Authors: Judith A.C. Rietjens, Agnes van der Heide, Astrid M. Vrakking, Bregje D. Onwuteaka-Philipsen, Paul J. van der Maas, Gerrit van der Wal
Journal: Annals of Internal Medicine (2004)

Background: Terminal sedation in patients nearing death is an important issue related to end-of-life care. Objective: To describe the practice of terminal sedation in the Netherlands. Design: Face-to-face interviews. Setting: The Netherlands. Participants: Nationwide stratified sample of 482 physicians; 410 responded and 211 of these reported characteristics of their most recent terminal sedation case. Measurements: Physician reports of frequency of terminal sedation (defined as the administration of drugs to keep the patient in deep sedation or coma until death, without giving artificial nutrition or hydration), characteristics of the decision-making process, drugs used, the estimated life-shortening effect, and frequency of euthanasia discussions. Results: Of respondents, 52% (95% CI, 48% to 57%) had ever used terminal sedation. Of the 211 most recent cases, physicians used terminal sedation to alleviate severe pain in 51% of patients (CI, 44% to 58%), agitation in 38% (CI, 32% to 45%), and dyspnea in 38% (CI, 32% to 45%). Physicians reported discussing with patients the decision to use deep sedation in 59% of the 211 most recent cases (CI, 52% to 66%) and the decision to forgo artificial nutrition or hydration in 34% (CI, 28% to 41%). Hastening death was partly the intention of the physician in 47% (CI, 41% to 54%) of cases and the explicit intention in 17% (CI, 13% to 22%) of cases. Limitations: The generalizability of physician reports about their most recent cases to all terminal sedation cases is uncertain. In addition, the findings are subject to recall bias and may not apply to other geographic settings. Conclusions: Terminal sedation precedes a substantial number of deaths in the Netherlands. In about two thirds of most recently reported cases, physicians indicated that in addition to alleviating symptoms, they intended to hasten death.
Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance
Authors: Chong Wee Liew, Jeremie Boucher, Jit Kong Cheong, Cecile Vernochet, Ho-Jin Koh, Cristina Mallol, Kristy Townsend, Dominique Langin, Dan Kawamori, Jiang Hu, Yu-Hua Tseng, Marc K Hellerstein, Stephen R Farmer, Laurie Goodyear, Alessandro Doria, Matthias Blüher, Stephen I-Hong Hsu, Rohit N Kulkarni
Journal: Nature Medicine (2013)
Fecal IgE levels in infants at 1 month of age as indicator of atopic disease
Authors: K. Sasai, S. Furukawa, K. Kaneko, K. Yabuta, M. Baba
Journal: Allergy (1994)

Fecal IgE levels were investigated in 165 asymptomatic infants at 1 month of age under two nutritional regimens, breast‐feeding and formula feeding, and the possibility of predicting by fecal IgE levels the onset of atopic disease was studied in these infants. IgE levels were measured by time‐resolved fluoroimmunometric assay. IgE antibodies are detectable in fecal extracts, and we have already reported that IgE levels are increased in food‐allergy patients after administration of food allergens, and this increase in fecal IgE levels may be a specific consequence of the local immune response to food‐allergen stimulation in the gut mucosa. The presence of atopic disease and the feeding method during the nursing period were surveyed by questionnaire in 89 of these 165 infants when they were 18 months old. In an analysis of the present results, IgE values above 0.015 U/ml, the lower limit of measurement, were considered to be high. Forty‐eight (29%) of the 165 subjects showed a high fecal IgE level. Thirty‐seven (35%) of 105 formula‐fed infants had high fecal IgE levels, whereas only 11 (18%) of 60 breast‐fed infants had high levels (P&lt;0.05). With respect to atopic family history, 30(39%) of the 77 infants with atopic family history had high fecal IgE levels, as compared with 18 (20%) of the 88 infants without atopic family history ( P &lt;0.01). When the relationship between fecal IgE levels at 1 month of age and presence of atopic disease in the first 18 months was investigated, the prevalence of atopic disease was significantly higher in subjects with high fecal IgE levels (50%) than in subjects with low fecal IgE levels (14%) ( P &lt;0.01). We conclude that cow's milk proteins or dietary antigens in breast milk consumed by infants, in addition to genetic predisposition, may stimulate IgE immune response in the developmental gut mucosa, and that fecal IgE level at 1 month of age is an important and noninvasive factor for predicting the development of atopic disease during infancy and early childhood.
Implications of bevacizumab discontinuation in adults with recurrent glioblastoma
Authors: Mark D. Anderson, Mohamed A. Hamza, Kenneth R. Hess, Vinay K. Puduvalli
Journal: Neuro-Oncology (2014)

Patients with recurrent glioblastoma benefiting from bevacizumab are often treated indefinitely due to concerns regarding rebound tumor recurrence upon discontinuation. However, treatment is discontinued for reasons other than disease progression in a subset of these patients, the characteristics and outcomes of which are poorly defined. Of 342 adults with recurrent glioblastoma in our database treated with bevacizumab, 82 received treatment for ≥6 months; of these, bevacizumab was discontinued for reasons other than tumor progression in 18 patients (Bev-D) and for disease progression in the remainder (Bev-S). The impact of discontinuation on outcome was assessed with discontinuation as a time-dependent covariate in a Cox hazards model for progression-free survival. There was no difference in hazard rates for progression between Bev-D and Bev-S groups; the adjusted hazard ratio for progression using discontinuation as a time-dependent covariate was 0.91 (95% CI:0.47, 1.78). The median PFS after bevacizumab-discontinuation was 27 weeks (95% CI:15-NR). At progression, a higher proportion of Bev-D patients had local progression compared with the Bev-S patients. Salvage therapy in Bev-D patients yielded a PFS-26 weeks of 47% (95% CI:23%–94%) with a median PFS of 23 weeks (95% CI:12-NR), vs. 5% (95% CI: 1%–21%) and 9 weeks (95% CI: 6–11) in Bev-S patients (HR:0.3;CI, 0.1–0.6) (P = .0007). Bevacizumab discontinuation unrelated to disease progression does not appear to cause rebound recurrence or worsen PFS in patients who benefit from bevacizumab. Additionally, Bev-D patients had an improved response to salvage therapy, findings which provide a strong basis for a prospective study.
Simplified diagnostic procedure for obstructive sleep apnoea syndrome: lower subsequent compliance with CPAP
Authors: J Krieger, E Sforza, C Petiau, T Weiss
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate whether a simplified diagnostic procedure based on ambulatory monitoring with MESAM IV altered subsequent compliance with continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) patients. During a period of 16 months, 60 patients with symptoms evocative of OSA and positive MESAM recording were prescribed CPAP after titration with standard polysomnography. Compliance was followed during 2 yrs based on built-in time counters and was compared with the compliance in two comparison groups: an equal number of equally severely affected patients diagnosed with standard polysomnography during the 18 months (8 months before and 8 months after) preceding and following the study period and a group of 48 patients with an estimated similar apnoea/hypopnoea index but less typical clinical and/or MESAM features, diagnosed as having OSA based on polysomnography during the study period. The three groups were not different by age, body mass index, or sleepiness score. Patients diagnosed with the ambulatory procedure had higher drop-out rates (21.7% versus 10% and 6.25%; p&lt;0.05) and lower rates of use of their CPAP (43+/-0.3 h x night(-1)) than any of the control groups (53+/-0.2 and 5.6+/-0.2 h x night(-1), p&lt;0.05). In conclusion, there is a risk that ambulatory diagnostic procedures alter the relationship of patients to their disease and/or the medical staff so that subsequent compliance with treatment may be decreased. The greatest care concerning compliance should be taken before an ambulatory-based diagnostic procedure is implemented.