tbuckley/cabot-search huggingface dataset:
Microvascular Complications in Cystic Fibrosis–Related Diabetes
Authors: Sarah Jane Schwarzenberg, William Thomas, Timothy W. Olsen, Trish Grover, David Walk, Carlos Milla, Antoinette Moran
Journal: Diabetes Care (2007)

The incidence of cystic fibrosis-related diabetes (CFRD) and the prevalence of diabetic microvascular complications were determined at the University of Minnesota.Cystic fibrosis patients have undergone annual oral glucose tolerance testing since 1990. Database review was performed to determine diabetes duration and the results of annual urine albumin-to-creatinine ratio (U(alb:Cr)) screening and dilated retinal exams. In addition, 59 individuals underwent detailed retinopathy, nephropathy, neuropathy, and gastroenteropathy screening.During 1990-2005, 775 patients aged > or = 6 years were followed. CFRD was diagnosed by an oral glucose tolerance test or fasting hyperglycemia in 285 subjects (52% female), 64% of whom had fasting hyperglycemia. Most patients with CFRD without fasting hyperglycemia progressed to CFRD with fasting hyperglycemia over time. No subject with CFRD without fasting hyperglycemia had retinopathy or abnormal U(alb:Cr). In CFRD subjects with fasting hyperglycemia and diabetes for > or = 10 years, 14% had microalbuminuria and 16% had retinopathy. Autonomic neuropathy and gastrointestinal symptoms each were seen in 52% and somatic abnormalities in 22% of patients with or without fasting hyperglycemia.Diabetic microvascular complications occur in CFRD, although the prevalence of retinopathy and nephropathy appears to be less than that found in other forms of diabetes. Annual complication screening should occur after known diabetes duration of 5 years in patients with CFRD with fasting hyperglycemia.
In vitro antitumor activity of the novel marine agent, Ecteinascidin-743 (ET-743, NSC-648766) against human tumors explanted from patients
Authors: E. Izbicka, R. Lawrence, E. Raymond, G. Eckhardt, G. Faircloth, J. Jimeno, G. Clark, D.D. VonHoff
Journal: Annals of Oncology (1998)
Controlled relaxation. II. Clinical management of muscle-relaxant administration
Authors: R. H. De Jong
Journal: JAMA (1966)

Strength of contraction of small muscles of the hand, foot, or face elicited by electrical stimulation of the motor nerve was estimated during administration of a muscle relaxant in 65 anesthetized patients. The purpose was to evaluate whether relative strength of muscle contraction provided a useful indication of surgical requirements. Maintaining a flicker of evoked muscular contraction, shown to represent 5% to 10% of normal neuromuscular transmission, provided profound abdominal muscle relaxation and adequate operating conditions in 63 of 65 patients. Normal neuromuscular transmission had returned in 29 patients at termination of anesthesia. Transmission was restored in an additional 31 patients by giving neostigmine. In five patients relaxant action was not or could not be reversed by neostigmine. In the latter group respiration was assisted until tests of neuromuscular function showed normal function.
Head, face and neck injury in youth rugby: incidence and risk factors
Authors: A S McIntosh, P McCrory, C F Finch, R Wolfe
Journal: British Journal of Sports Medicine (2008)

In this study, the incidence of head, neck and facial injuries in youth rugby was determined, and the associated risk factors were assessed.Data were extracted from a cluster randomised controlled trial of headgear with the football teams as the unit of randomisation. No effect was observed for headgear use on injury rates, and the data were pooled.General school and club-based community competitive youth rugby in the 2002 and 2003 seasons.Young male rugby union football players participating in under-13, under 15, under 18 and under 21 years competitions. Eighty-two teams participated in year 1 and 87 in year 2.Injury rates for all body regions combined, head, neck and face calculated for game and missed game injuries.554 head, face and neck injuries were recorded within a total of 28 902 h of rugby game exposure. Level of play and player position were related to injury risk. Younger players had the lowest rates of injury; forwards, especially the front row had the highest rate of neck injury; and inside backs had the highest rate of injuries causing the player to miss a game. Contact events, including the scrum and tackle, were the main events leading to injury.Injury prevention must focus on the tackle and scrum elements of a youth rugby game.
Peripheral Arterial Disease in Randomized Trial of Estrogen With Progestin in Women With Coronary Heart Disease
Authors: Judith Hsia, Joel A. Simon, Feng Lin, William B. Applegate, Molly T. Vogt, Donald Hunninghake, Margaret Carr
Journal: Circulation (2000)

Postmenopausal estrogen use has been associated with reduced carotid atherosclerosis in observational studies, but this relationship has not been confirmed in a clinical trial. The impact of estrogen on atherosclerotic disease in other peripheral arteries is unknown.Postmenopausal women with coronary heart disease (CHD) and an intact uterus (n=2763) were randomly assigned to conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) daily or to placebo in a secondary CHD prevention trial. This analysis focuses on incident peripheral arterial procedures and deaths in the 2 treatment groups; peripheral vascular disease was a predefined secondary outcome. During a mean of 4.1 years of follow-up, 311 peripheral arterial events were reported in 213 women, an annual incidence of 2.9%. The number of women who had peripheral arterial events was 99 among those assigned to active estrogen/progestin and 114 among those assigned to placebo, a nonsignificant difference (relative hazard 0. 87, 95% CI 0.66 to 1.14). In the placebo group, hypertension and diabetes mellitus were independently associated with higher rates of peripheral arterial events, and plasma HDL cholesterol and body mass index were associated with lower rates of peripheral arterial events. In the estrogen/progestin group, current smoking and diabetes were independent predictors of peripheral arterial events. Incident peripheral arterial disease was not a significant predictor of coronary, cardiovascular, or total mortality.Treatment with oral conjugated estrogen plus medroxyprogesterone acetate was not associated with a significant reduction in incident peripheral arterial events in postmenopausal women with preexisting CHD.
Transplacental influence of the thymus.
Authors: P McCullagh
Journal: The Journal of Experimental Medicine (1977)

Peripheral blood lymphocyte levels attained in adult rats that had been thymectomized at birth were markedly reduced if the two or three immediately preceding generations of rats from which they were bred had been thymectomized as neonates. The capacity of thymectomized animals to survive to adult life was also drastically reduced if they were bred from thymectomized stock. Pregnancy as a result of mating with syngeneic or allogeneic males produced an ephemeral increase in peripheral blood lymphocyte levels of third and fourth generation thymectomized females. These observations are most readily explicable on the basis of a thymus-derived humoral influence acting directly or indirectly to influence the circulating lymphocyte population.
Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis.
Authors: J J Egan, J P Stewart, P S Hasleton, J R Arrand, K B Carroll, A A Woodcock
Journal: Thorax (1995)

BACKGROUND--Cryptogenic fibrosing alveolitis (synonymous with idiopathic pulmonary fibrosis) is a clinically heterogeneous condition in which the precipitating factor is unclear. Both environmental and infective factors have been implicated. An association between Epstein-Barr virus (EBV) and cryptogenic fibrosing alveolitis was suggested over a decade ago by a study based on EBV serology, but the significance of this has been unclear. METHODS--Lung tissue obtained surgically from patients (n = 20) with cryptogenic fibrosing alveolitis was investigated for evidence of EBV replication and compared with lung tissue from 21 control patients. Fourteen of the 20 patients had received no specific therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV viral capsid antigen (VCA) and gp 340/220 antigen, which are expressed during the lytic phase of the EBV life cycle, were studied. RESULTS--Fourteen (70%) of the 20 patients with cryptogenic fibrosing alveolitis were positive for both EBV VCA and gp 340/220 compared with two (9%) of the 21 controls. In the patients with cryptogenic fibrosing alveolitis viral replication was localised to pulmonary epithelial cells using epithelial cell markers, and immunohistochemical analysis confirmed the staining to be within type II alveolar cells. CONCLUSIONS--This is the first report of in vivo EBV replication within epithelial cells of the lower respiratory tract in an immunocompetent human host. Furthermore, this suggests that EBV may be an immune trigger or contribute to lung injury in cryptogenic fibrosing alveolitis, thus offering a potential new avenue of treatment.
Sputum CD34<sup>+</sup>IL-5Rα<sup>+</sup> Cells Increase after Allergen
Authors: Sandra C. Dorman, Ann Efthimiadis, Irene Babirad, Rick M. Watson, Judah A. Denburg, Frederick E. Hargreave, Paul M. O'Byrne, Roma Sehmi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Eosinophil lineage–committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34+ and CD34+IL-5Rα+ cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilia and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34+ cells in normal control subjects compared with subjects with asthma. Sputum CD34+ cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34+IL-5Rα+ cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.
Dietary Soy Protein Effects on Inherited Polycystic Kidney Disease Are Influenced by Gender and Protein Level
Authors: HAROLD M. AUKEMA, IHSAN HOUSINI, JEAN M. RAWLING
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The effects of dietary soy protein compared to casein were examined in male and female CD1- pcy/pcy ( pcy ) mice with polycystic kidney disease. Animals 10 wk of age were fed purified diets containing either soy protein isolate or casein given at a level of 17.4 or 6% protein. After 13 wk on the diets, body weights and serum concentrations of albumin and protein indicated that protein nutrition was adequate on all diets. Overall, animals fed soy protein versus casein had 28% lower ( P = 0.0037) relative kidney weights (g/100 g body wt), 37% lower ( P = 0.0089) cyst scores (% cyst area × relative kidney weight), and 25% less ( P = 0.0144) kidney water (g). Dietary protein reduction resulted in 30% lower ( P = 0.0010) relative kidney weights, 25% lower ( P = 0.0327) cyst scores, and 35% less ( P = 0.0001) kidney water. Analysis of interactions between main effects revealed that the effects of soy protein on kidney size were significant only in females, and that effects of soy protein on cyst score were significant only in animals on the low protein diets. In addition, differences in kidney weights and cyst score due to protein reduction were significant in animals fed soy protein, but not in those fed casein as the protein source. These results show that both dietary protein source and level significantly affect polycystic kidney disease in pcy animals, with the effects of dietary soy protein being most pronounced in female animals fed the low protein diets and the effects of protein reduction being most pronounced in animals fed soy protein-based diets.
Transferrin Synthesis Is Increased in Nephrotic Patients Insufficiently to Replace Urinary Losses
Authors: BERTHIL H. C. M. T. PRINSEN, MONIQUE G. M. DE SAIN-VAN DER VELDEN, GEORGE A. KAYSEN, HELMA W. H. C. STRAVER, HERMAN J. M. VAN RIJN, FRANS STELLAARD, RUUD BERGER, TON J. RABELINK
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The urinary loss of transferrin is sufficient to reduce plasma transferrin concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia in the nephrotic syndrome is, however, unknown. In the present study, synthesis rate of transferrin was measured in vivo in nephrotic patients ( n = 7) compared with control subjects ( n = 6) using L-[1- 13 C]-valine. Plasma transferrin and iron concentration in the patients were significantly lower than in control subjects (transferrin, 1.39 ± 0.08 versus 2.57 ± 0.11 g/L, P &lt; 0.0001; iron, 10.2 ± 0.8 versus 21.1 ± 4.5 μmol/L, P = 0.02). Furthermore, albuminuria correlated with transferrinuria (r 2 = 0.901, P = 0.001). The absolute synthesis rate of transferrin was increased in the patients (10.0 ± 1.1 versus 7.4 ± 0.7 mg/kg per d, P = 0.07), although this value failed to achieve significance. C-reactive protein, plasma iron, and proteinuria did not correlate with transferrin synthesis. In contrast, transferrin synthesis correlated with albumin synthesis (r 2 = 0.648, P = 0.03; n = 7). The present study indicates that increased transferrin synthesis occurs in nephrotic patients but is insufficient to compensate for urinary losses. Because, overall, no significant relationship was found between transferrin synthesis and either C-reactive protein or iron, it is unlikely that inflammation suppresses or that iron deficiency stimulates increased transferrin synthesis in these patients. The correlation between transferrin synthesis and albumin synthesis suggests that transferrin synthesis is a component of a general response in hepatic protein synthesis in the nephrotic syndrome. This suggests that a therapeutic approach to maximize plasma transferrin concentrations in nephrotic patients should be aimed primarily at reducing urinary protein excretion.
Maturation of Cardiovagal Autonomic Function From Childhood to Young Adult Age
Authors: Zsuzsanna Lenard, Peter Studinger, Beatrix Mersich, Laszlo Kocsis, Mark Kollai
Journal: Circulation (2004)

Cardiovagal autonomic control declines with age in adult subjects, which is related in part to increasing stiffness of the barosensory vessel wall. It is not known, however, whether autonomic function changes with age in children.We studied 137 healthy subjects divided into 4 age groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years; and group 4, 19 to 22 years. Brachial artery pressure was measured by sphygmomanometry and continuous radial artery pressure and carotid artery pulse pressure (DeltaP) by applanation tonometry. The R-R interval was derived from the ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain indices, which indicate the extent of coupling between fluctuations in heart rate and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile distension (DeltaD) were measured by echo wall tracking; carotid compliance coefficient (CC) was defined as DeltaD/DeltaP and distensibility coefficient as 2DeltaD/DD . DeltaP. From group 1 to group 3, spontaneous indices increased significantly (18.1+/-1.7 versus 33.3+/-4.0; 14.4+/-1.1 versus 25.5+/-22; 12.9+/-1.1 versus 20.8+/-2.0; and 6.4+/-0.6 versus 16.2+/-1.4 ms/mm Hg [mean+/-SEM] for Seq+, Seq-, LFalpha, and LF(gain), respectively), with no significant changes afterward. CC and DC were inversely proportional to age (r=-0.49 and -0.62, respectively, P<0.001). The efficiency of neural integrative mechanisms, estimated as the ratio of spontaneous indices and CC, more than doubled from group 1 to group 3. Spontaneous indices were linearly related to measures of cardiac vagal activity.The increase in spontaneous indices from early childhood to adolescence, despite gradual stiffening of the carotid artery, may indicate improved cardiovagal autonomic function, which is most likely a result of maturation of neural mechanisms, attaining peak level at adolescence.
Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles
Authors: Lauren Howitt, Ivana Y. Kuo, Anthie Ellis, Daniel J. Chaston, Hee-Sup Shin, Pernille B. Hansen, Caryl E. Hill
Journal: Cardiovascular Research (2013)

As cardiovascular disease is characterized by reduced nitric oxide bioavailability, our aim was to determine the impact of this change on the mechanism underlying vascular tone of pressurized arteries in vitro and in vivo.We used pressurized cerebral and mesenteric arteries in vitro and skeletal muscle arterioles in vivo to study the contribution of L-type (1 µmol/L nifedipine) and T-type (1 µmol/L mibefradil, 3 µmol/L NNC 55-0396) calcium channels to vascular tone, following acute or chronic inhibition of nitric oxide. Acute inhibition with l-NAME (10 µmol/L) significantly increased the T-type, but not the L-type, channel contribution to vascular tone in vitro and in vivo, and altered the smooth muscle expression of the Cav3.1 and Cav3.2 T-type channels. In pressurized mesenteric arteries of Cav3.1ko and Cav3.2ko mice, acutely treated with l-NAME, the contribution of T-type channels relative to L-type channels was significantly reduced, compared with arteries from wild-type mice.Chronic l-NAME treatment (40 mg/kg/day; 14-18 days) increased blood pressure, vascular superoxide, and the contribution of T-type channels to vascular tone in vivo. The latter was reversed by acute scavenging of superoxide with tempol (1 mmol/L), or inhibition of NADPH oxidase with apocynin (500 µmol/L) or DPI (5 µmol/L).We conclude that nitric oxide deficit produces a significant increase in the contribution of Cav3.1 and Cav3.2 T-type calcium channels to vascular tone, by regulating the bioavailability of reactive oxygen species produced by NADPH oxidase. Our data provide evidence for a novel causal link between nitric oxide deficit, oxidative stress, and T-type calcium channel function.
Plasma Brain Natriuretic Peptide as a Prognostic Indicator in Patients With Primary Pulmonary Hypertension
Authors: Noritoshi Nagaya, Toshio Nishikimi, Masaaki Uematsu, Toru Satoh, Shingo Kyotani, Fumio Sakamaki, Mikio Kakishita, Kengo Fukushima, Yoshiaki Okano, Norifumi Nakanishi, Kunio Miyatake, Kenji Kangawa
Journal: Circulation (2000)

Background —Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension (PPH). Methods and Results —Plasma BNP was measured in 60 patients with PPH at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (≥150 pg/mL) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves ( P &lt;0.05). Plasma BNP in survivors decreased significantly during the follow-up (217±38 to 149±30 pg/mL, P &lt;0.05), whereas that in nonsurvivors increased (365±77 to 544±68 pg/mL, P &lt;0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (≥180 pg/mL) than for those with an inframedian value ( P &lt;0.0001). Conclusions —A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality rates in patients with PPH.
A Phase I Dose Escalation and Expansion Study of the Anticancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors
Authors: David C. Smith, Peter D. Eisenberg, Georgy Manikhas, Rashmi Chugh, Matthew A. Gubens, Robert J. Stagg, Ann M. Kapoun, Lu Xu, Jakob Dupont, Branimir Sikic
Journal: Clinical Cancer Research (2014)

Abstract Purpose: This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies. Experimental Design: Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5, or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days. Results: Fifty-five patients received demcizumab (15 weekly, 18 every other week, 21 expansion cohort, 1 loading dose). No more than one DLT was seen at any dose level. The MTD was not reached for either schedule. Treatment-related adverse events occurring in &amp;gt;10% of patients were hypertension or blood pressure increased (47%), fatigue (31%), anemia (22%), headache (20%), nausea (13%), hypoalbuminemia (11%), dizziness (11%), and dyspnea (11%). One patient dosed at 2.5 mg/kg developed reversible right-sided heart failure after 63 days on treatment and 4 dosed at 10 mg/kg developed congestive heart failure after ≥98 days on treatment. Five patients were hospitalized with bleeding episodes (2 episodes of tumor-associated bleeding). Sixteen of 25 (64%) evaluable patients at 10 mg/kg had evidence of stabilization of disease or response. Conclusion: Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure. Clin Cancer Res; 20(24); 6295–303. ©2014 AACR.