tbuckley/cabot-search huggingface dataset:
Development of asthma in a Swedish birth cohort up to the age of 32-34 years
Authors: Hartmut Vogt, Lennart Bråbäck, Karin Fälth-Magnusson, Lennart Nilsson
Journal: European Respiratory Journal (2013)

Background: Asthma in adulthood could be programmed in early life. However, the number of cohort studies following the development of asthma from childhood up to adulthood is so far limited and the findings have been contradictory.

Objective: To evaluate the development of asthma over time in a cohort born in the mid 1970-ies.

Material & Methods: A population-based, non-selected birth cohort comprising 1,701 consecutively born children at a University Hospital in Southeast Sweden. At the age of 6–7 and 10–11 years of age an asthma diagnosis was confirmed by parental questionnaires, telephone check-ups and the review of available medical records. Information on dispensed asthma medication (inhaled corticosteroids and/or leucotriene antagonists) at the ages of 32-34 years was collected from the Swedish Prescribed Drug Register after linkage of data at an individual level.

Results: In all, 1,661 individuals (97.6%) of the original birth cohort could be linked to the Swedish Prescribed Drug Register and 48 individuals were diagnosed with asthma at the two follow-ups in childhood. At the age of 32-34 years, 60 individuals were dispensed inhaled corticosteroids or leucotriene antagonists. Out of those, 49 individuals had not been diagnosed with asthma at the check-ups during childhood.

Conclusion: The majority of the individuals with asthma in childhood had not been dispensed asthma medication in adulthood. The findings suggest that a major part of the individuals with asthma medication at the age of 32-34 years had developed asthma during or after adolescence.
Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients.
Authors: M R O'Donnell, G M Schmidt, B R Tegtmeier, C Faucett, J L Fahey, J Ito, A Nademanee, J Niland, P Parker, E P Smith
Journal: Journal of Clinical Oncology (1994)

To identify risk factors that might predict for systemic fungal infections in marrow transplant recipients within the first 100 days and to assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia and infection with invasive Aspergillus species in patients at risk.A retrospective analysis of transplant outcomes for 331 allogeneic marrow recipients transplanted between 1983 and 1989 was performed to identify patients who might be at increased risk of fungal infection. Factors analyzed included disease, remission status, transplant regimen, graft-versus-host disease (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3 months posttransplant was begun in 1987 to evaluate its utility in reducing systemic mycoses.There were 18 episodes of candidemia and 18 systemic mycoses documented by blood or tissue culture or by biopsy. The initiation of high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD prophylaxis in 1986 was identified as the most important risk factor for fungal infections, with a sixfold increase in infections as compared with the previous GVHD regimen (P < .0001); this was despite a significant decrease in the incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced the incidence of fungal infections from 30% to 9% (P = .01) without renal toxicity. Cyclosporine levels were lower in the patients who received amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02). Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II to IV GVHD (P = .01) were also identified as risk factors for fungal infection.Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.
The Natural History of Lung Function after Lung Transplantation for α<sub>1</sub>-Antitrypsin Deficiency
Authors: Amit Banga, Thomas Gildea, Jeevanantham Rajeswaran, Haala Rokadia, Eugene H. Blackstone, James K. Stoller
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Lung transplantation (LT) is an established treatment for end-stage lung diseases, including chronic obstructive pulmonary disease (COPD) associated with α1-antitrypsin deficiency (AATD).Objectives: We sought to compare the post-transplantation course of patients with AATD and AAT-replete COPD.Methods: Between June 1991 and January 2008, a total of 231 patients with AAT-replete COPD and 45 with AATD underwent LT at Cleveland Clinic. Data reviewed included baseline recipient, donor, and surgical data; all spirometry evaluations; acute cellular rejection (ACR) events; and survival data. Endpoints included temporal change in FEV1, severity of ACR, and survival. A longitudinal temporal decomposition model was used for analysis.Measurements and Main Results: Comparison of overall rates of FEV1 decline in AATD and AAT-replete patients with COPD showed no significant differences (P > 0.09). However, although the single LT patients had similar trends in FEV1 in both groups, patients with AATD with double LT declined faster (P < 0.002) than the AAT-replete patients. No differences in the frequency or severity of ACR episodes were observed (P = 0.32). Furthermore, there was no difference in early or late mortality between patients with AATD and patients with AAT-replete COPD (P > 0.09).Conclusions: Although overall the post-LT FEV1 slope, severity of ACR, and survival among patients with AATD is similar to that of AAT-replete patients with COPD, patients with AATD with double LT have a faster rate of FEV1 decline. These findings support the eligibility of patients with AATD for LT, and suggest the need for additional studies to better understand the difference between single and double LT in AATD.
Vitamin A and the Radiation Response of Experimental Tumors: An Immune-Mediated Effect&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: I. F. Tannock, H. D. Suit, Nancy Marshall
Journal: JNCI Journal of the National Cancer Institute (1972)

Radiation dose-response assays were performed for 2 tumors; the endpoint was the mean radiation dose yielding local tumor control in 50% of animals (TCD50). Injection of vitamin A after local irradiation of an antigenic fibrosarcoma in normal animals gave a 15–20% reduction in TCD50. There was no effect of vitamin A after irradiation of the fibrosarcoma in immune-suppressed animals or against a mammary carcinoma of very weak antigenicity. The TCD50 for the fibrosarcoma in mice actively sensitized to this tumor before transplantation was higher than in unsensitized animals, which suggested immunological enhancement; in such mice, injection of vitamin A after local irradiation reduced the TCD50 by 25%. The effect of vitamin A on radiation response of 2 normal tissues was assayed. Surviving fraction of intestinal crypt cells and the acute reaction of skin were the same in vitamin A and saline-injected mice exposed to a single dose of radiation. Administration of vitamin A had no effect on TD50 (i.e., the mean number of tumor cells required to generate tumors in 50% of animals) when a simple suspension of fibrosarcoma cells was injected into normal mice. However, the drug abolished the growth-enhancing effect observed when lethally irradiated cells were admixed with the standard cell suspension. After irradiation of an antigenic tumor, radiation-damaged cells prior to their lysis may compete with surviving cells for a limited immune-rejection response. We suggest that vitamin A acts mainly by increasing the rate of lysis of damaged cells, thus concentrating the immune response against cells surviving irradiation, but that it may also directly stimulate the immune-rejection response in animals sensitized to their tumors before transplantation.
Diurnal variation in FEV1 after heart-lung transplantation
Authors: JF Morrison, TW Higenbottam, TJ Hathaway, C Clelland, JP Scott, J Wallwork
Journal: European Respiratory Journal (1992)

We have examined the diurnal variation in forced expiratory volume in one second (FEV1) in 25 heart-lung transplantation patients over a four week period in order to study the pathophysiological mechanisms underlying the increased mortality and morbidity which occurs at night in asthma. These patients do not have pulmonary autonomic nervous reflexes, but often have muscarinic receptor hypersensitivity. They also develop mixed cell infiltration of the lung tissue in the course of infection or rejection. Thus, they show many features in common with asthma. Seventeen patients (68%) showed a significant diurnal variation in airway calibre (mean amplitude of FEV1 was 4.6% (SD 3.7%)), which is similar to that reported in normal adults. One patient had a diurnal variation of 34.5% during an episode of rejection. This variation fell to 6.9% after steroid therapy, a change often seen in asthma. There was a correlation between increased amplitude of the variation and the presence in transbronchial biopsies of airway submucosal eosinophils and lymphocytes, associated with a histological diagnosis of acute rejection and with epithelial damage. No association was seen with muscarinic receptor sensitivity. The variation in FEV1 showed no alteration from the normal day/night synchronization, and the peak values were around 1300 h. We conclude that the diurnal variation in FEV1 after heart-lung transplantation is not dependent on autonomic nerve reflexes or muscarinic receptor sensitivity, but is related to the consequences of inflammation described above.
Effect of low-dose aspirin on thromboxane production and the antihypertensive effect of captopril.
Authors: S R Smith, T M Coffman, L P Svetkey
Journal: Journal of the American Society of Nephrology (1993)

Some of the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is through decreased kinin degradation, leading to enhanced production of vasodilator arachidonic acid metabolites. It was reasoned that if ACE inhibition also leads to an increase in the production of the potent vasoconstrictor thromboxane A2, then maneuvers that selectively inhibit thromboxane production without reducing prostaglandins (PG) E2 + PGI2 might enhance the antihypertensive effect of ACE inhibition. This double-blinded, randomized, crossover study was therefore undertaken to determine: (1) if captopril increases platelet and/or renal thromboxane production; and (2) if low-dose aspirin enhances the antihypertensive effect of captopril. Patients with mild essential hypertension and no other significant medical problems were studied. In a double-blinded, random order, patients took captopril alone (25 mg every 12 h) for 2 wk and captopril plus aspirin (75 mg/day) for another 2 wk. Active treatment periods were preceded by 2 wk of single-blind placebo. Fifteen patients with a mean age of 53 yr and an average mean arterial pressure (MAP) of 114 +/- 8 (+/- SD) mm Hg were studied. Serum thromboxane B2 was higher (P < 0.05) during treatment with captopril/placebo (600 +/- 46 (+/- SE) pg/mL) than during the two washout periods combined (420 +/- 57 and 553 +/- 78) and was lowest (P < 0.0005) during treatment with captopril/aspirin (302 +/- 36). Captopril treatment significantly increased the urinary excretion of PGE2 (P = 0.038). Captopril/placebo significantly lowered MAP (P < 0.05) to 105.0 +/- 3.7 mm Hg compared with the washout period. However, the addition of aspirin to captopril caused no additional lowering of MAP (105.2 +/- 2.8 mm Hg). It was concluded that treatment with captopril does increase platelet thromboxane production. However, lowering platelet thromboxane with low doses of aspirin may not enhance the antihypertensive effect of captopril.
The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man.
Authors: J R Stratton, M A Pfeifer, J B Halter
Journal: Circulation (1987)

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Hormonal Status of Breast Cancer. II. Abnormal Urinary Steroid Excretion2
Authors: Mitsuo Kodama, Toshiko Kodama, Minoru Yoshida, Ryozo Totania, Kunio Aoki
Journal: JNCI Journal of the National Cancer Institute (1975)

The urinary excretion of 14 neutral steroids was measured by gas-liquid chromatography in women with early and advanced breast cancer, in women with early uterine cancer, and in healthy women from urban and rural districts. The premenopausal patients with early breast cancer excreted subnormal amounts of five steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, pregnanetriol, and tetrahydrocorticosterone) and increased amounts of tetrahydrocortisol as compared with the normal subjects of corresponding ages. From our findings, a new parameter was proposed by which a premenopausal breast-cancer patient was separated from the control. Postmenopausal breast-cancer patients excreted greater amounts of five steroids (one steroid from 17-ketosteroids and four from 17-hydroxycorticoids) than the corresponding controls. The discrepancy between premenopausal and postmenopausal breast cancer was tentatively related to ovarian-adrenal dysfunction in the course of aging. Oophorectomy induced a long-lasting tumor regression only in patients with a high value for the ratio of 11-deoxy-17-ketosteroid to 17-hydroxycorticosteroid in urine taken before surgery; the ratio in the responsive patients decreased remarkably after surgery. A constitutional change in 17-ketosteroids, as observed in a postmenopausal breast-cancer patient and a premenopausal healthy woman of urban origin, favored the geographic importance in the genesis of breast malignancy. The steroid abnormalities in uterine cancer were distinguishable from those of breast cancer in both premenopausal and postmenopausal women.
Sociodemographic and Geographic Predictors of Quality of Care in United States Patients With End‐Stage Renal Disease Due to Lupus Nephritis
Authors: Laura C. Plantinga, Cristina Drenkard, Rachel E. Patzer, Mitchel Klein, Michael R. Kramer, Stephen Pastan, S. Sam Lim, William M. McClellan
Journal: Arthritis & Rheumatology (2015)

Objective To describe end‐stage renal disease (ESRD) quality of care (receipt of pre‐ESRD nephrology care, access to kidney transplantation, and placement of permanent vascular access for dialysis) in US patients with ESRD due to lupus nephritis (LN‐ESRD) and to examine whether quality measures differ by patient sociodemographic characteristics or US region. Methods National surveillance data on patients in the US in whom treatment for LN‐ESRD was initiated between July 2005 and September 2011 (n = 6,594) were analyzed. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were determined for each quality measure, according to sociodemographic factors and US region. Results Overall, 71% of the patients received nephrology care prior to ESRD. Black and Hispanic patients were less likely than white patients to receive pre‐ESRD care (OR 0.73 [95% CI 0.63–0.85] and OR 0.73 [95% CI 0.60–0.88], respectively) and to be placed on the kidney transplant waitlist within the first year after the start of ESRD (HR 0.78 [95% CI 0.68–0.91] and HR 0.82 [95% CI 0.68–0.98], respectively). Those with Medicaid (HR 0.51 [95% CI 0.44–0.58]) or no insurance (HR 0.36 [95% CI 0.29–0.44]) were less likely than those with private insurance to be placed on the waitlist. Only 24% had a permanent vascular access, and placement was even less likely among the uninsured (OR 0.62 [95% CI 0.49–0.79]). ESRD quality‐of‐care measures varied 2–3‐fold across regions of the US, with patients in the Northeast and Northwest generally having higher probabilities of adequate care. Conclusion LN‐ESRD patients have suboptimal ESRD care, particularly with regard to placement of dialysis vascular access. Minority race/ethnicity and lack of private insurance are associated with inadequate ESRD care. Further studies are warranted to examine multilevel barriers to, and develop targeted interventions to improve delivery of, care among patients with LN‐ESRD.
Relation of tumor-cell ploidy to survival in children with medulloblastoma.
Authors: A J Gajjar, R L Heideman, E C Douglass, L E Kun, E H Kovnar, R A Sanford, D L Fairclough, D Ayers, A T Look
Journal: Journal of Clinical Oncology (1993)

PURPOSE To assess the value of tumor-cell ploidy as a predictor of survival in medulloblastoma. PATIENTS AND METHODS Ploidy determinations were based on the flow-cytometric analysis of cellular DNA content in fresh tumor specimens taken from 34 consecutively treated children with newly diagnosed medulloblastoma. Patients were assigned a high or low risk of failure depending on tumor size and invasiveness, and the presence or absence of metastatic disease. Treatment consisted of radiotherapy, with or without chemotherapy, according to institutional or cooperative group protocols. RESULTS Univariate analysis of candidate prognostic factors showed that only tumor-cell ploidy and clinical risk group had a statistically significant influence on survival. Patients with hyperdiploid stem lines (n = 9) had significantly longer survival times (P = .04) than did those with diploid lines (n = 20). The estimated 5-year survival probabilities (+/- SE) for these two subgroups were 89% +/- 11% and 48% +/- 13%, respectively. Although clinical risk status (high v low) showed essentially the same predictive strength as ploidy, the two features identified largely nonoverlapping subgroups. Thus, within the clinical high-risk group, it was possible to distinguish hyperdiploid patients whose 5-year survival rate (83% +/- 15%) was comparable to that of patients with localized, low-risk tumors. CONCLUSION This prospective study indicates that both ploidy and clinical risk group are important prognostic factors in medulloblastoma. Their combined use at diagnosis would distinguish patients who require more aggressive therapeutic intervention (diploid, clinical high-risk group) from those who could be expected to benefit most from standard treatment.
Dietary alteration of dihomogamma-linolenic acid/arachidonic acid ratio in a rat 5/6-renal-ablation model. The Nutrition &amp; Kidney Disease Research Group.
Authors: A J Ingram, A Parbtani, W F Clark, E Spanner, M W Huff, D J Philbrick, B J Holub, J W Scholey
Journal: Journal of the American Society of Nephrology (1996)

Interest in the modulation of renal diseases by polyunsaturated fatty acids (PUFA) led this group to examine the effects of borage oil (BO) and corn oil (CO) in the rat 5/6-renal-ablation model. BO is a rich source of gamma-linolenic acid (GLA; 18:3n-6), which is elongated to dihomogamma-linolenic acid (DGLA; 20:3n-6). CO is a rich source of linoleic acid (LA; 18:2n-6), a GLA and arachidonic acid (AA; 20:4n-6) precursor. The purpose of this study was to assess whether an increased DGLA:AA ratio as provided by BO would confer benefits beyond those provided by LA present in corn oil. Forty rats were used for the experiment. Seven rats were used for presurgery measurements. The remaining animals were subjected to 5/6 nephrectomy. Surviving rats (N = 30) were fed regular laboratory diet (RLD) for 7 days, at which time seven rats were used to obtain 1-wk postnephrectomy data. The remainder were then allocated to receive either RLD (N = 8), 15% BO (N = 8), or 15% CO (N = 7) diets for 20 wk. Body weight, renal phospholipid levels, renal function (proteinuria and GFR), glomerular histology, glomerular macrophage infiltration, urinary prostaglandin levels (thromboxane B2 (TxB2), 6-keto-PGF1 alpha), plasma lipid levels, and blood pressure were measured. Diets were well tolerated by all groups with a similar age-related gain in weight throughout the study. Efficacy of the PUFA diets was confirmed by alteration in renal tissue phospholipids; LA decreased in the RLD and BO groups, but not in the CO group. AA was higher in the BO and CO rats, but only the BO group showed a rise in GLA and DGLA incorporation. Proteinuria increased progressively in the RLD group but remained at 1-wk postsurgery levels in the BO and CO groups. Decline in GFR and mesangial expansion were significantly lessened by BO supplementation only. Both PUFA diets limited glomerulosclerosis and macrophage infiltration, but direct comparisons between BO and CO groups revealed significantly less glomerulosclerosis and macrophage infiltration in the BO group. Both BO and CO attenuated the rise in the TxB2 excretion rate and restored the 6-keto-PGF1 alpha:TxB2 ratio to the 1-wk postsurgery level. Plasma lipid levels rose in all groups, but the rise in cholesterol level was less in the BO and CO rats, CO being the most efficacious in this regard. BP increased progressively in RLD rats, but not in the BO and CO groups, BO providing a markedly greater hypotensive effect. In summary, both CO and BO supplemented PUFA diets limited glomerular injury in the renal-ablated rats. However, BO supplementation was more effective than CO supplementation at preserving GFR, limiting mesangial expansion and glomerulosclerosis, and reducing glomerular macrophage infiltration.
Isolation of T-Lymphocytes From Disaggregated Tumors, With High Purity and Good Percentage Recovery: Brief Communication23
Authors: Christopher B. Hansen, G. Yancey Gillespie, Stephen W. Russell
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Isolation of T-Lymphocytes From Disaggregated Tumors, With High Purity and Good Percentage Recovery: Brief Communication Get access Christopher B. Hansen, Christopher B. Hansen Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Yancey Gillespie, G. Yancey Gillespie Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen W. Russell Stephen W. Russell 7 7Address reprint requests to Dr. Russell. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 1, July 1977, Pages 273–275, https://doi.org/10.1093/jnci/59.1.273 Published: 01 July 1977 Article history Received: 21 September 1976 Accepted: 09 January 1977 Published: 01 July 1977