Volume accommodation by distension of gastric fundus (rabbit) and gastric corpus (cat)

In attempts to identify the structures of the proximal stomach responsible for volume accommodation, the dimensions of a herbivore (rabbit) were compared to those of a carnivore (cat) stomach at various degrees of filling. The total gastric surface area was similar in both species, but the proximal stomach of cats consisted primarily of the segment between the incisura angularis and the cardia (gastric corpus), while the proximal stomach of the rabbit was represented largely by the true fundus (segment orad to cardia). In both species, the muscle coat of the proximal stomach was thinner than that of the distal stomach, but this difference was more prominent in rabbits than in cats. In both species, the length and the angulation of the lesser curvature were little affected by filling of the stomach. Most length increases of the greater curvature occurred proximal to the cardia in the rabbit and proximal to the incisura angularis in the cat. Filling the stomach increased the length of the gastric circumference more steeply in the cat than in the rabbit. In both species, the stomachs shortened in their longitudinal axis in response to a drug that excites gastric smooth muscle (carbachol). A drug that inhibits gastric smooth muscle (isoproterenol) gave the stomach a more elongated shape. Cat stomachs ruptured at higher volumes and intragastric pressures than rabbit stomachs. In the cat, volume accommodation takes place in the transverse axis of the stomach, and parallel to the circular muscle fibers of the gastric corpus. In the rabbit, volume unfolds the gastric fundus in the longitudinal and transverse axes in parallel to the radiating course of the oblique muscle fibers.     

Diminished posttetanic potentiation in failing human myocardium

In heart failure a decreased function of SERCA2 has been demonstrated. The present study aimed at investigating the relation between sarcoplasmic reticulum-Ca²⁺-load (SR-Ca²⁺-load) and the activity of the SERCA2. SR-Ca²⁺ load was evaluated by measuring posttetanic potentiation (PTP) in human nonfailing (NF, n=10) and endstage failing myocardium (DCM, n=11). In addition, the effect of cyclopiazonic acid (CPA), a specific inhibitor of SERCA2, on PTP was studied in both NF and DCM. In crude membrane preparations from the same hearts the maximal SERCA2 activity was determined and correlated with the PTP. In failing myocardium the PTP was significantly reduced compared to nonfailing myocardium (13.7±0.75 mN/mm² vs. 17.1±1.55 mN/mm², p<0.05, ±SEM). When PTP was studied in the presence of increased extracellular Ca²⁺-concentrations, the difference between NF and DCM was further pronounced. CPA decreased PTP in both nonfailing and failing human tissue. The maximal SERCA2 activity was significantly reduced in failing myocardium (NF 267±18.5 nmol ATP/mg protein · min⁻¹ vs. DCM 191±13.4 nmol ATP/mg protein · min⁻¹, p<0.05, ± SEM). Correlation of the PTP and maximal SERCA2 activity revealed a close correlation between both parameters in NF and DCM. In summary, the presented results suggest that reduced SERCA2 activity in DCM influences posttetanic force potentiation probably through a reduced SR-Ca²⁺-load. Received: 30 July 1999 Returned for 1. revision: 9 September 1999 1. Revision received: 24 November 1999 Returned for 2. revision: 26 January 2000 2. Revision received: 26 April 2000 Accepted: 9 May 2000     

Monitoring carbon dioxide tension and arterial oxygen saturation by a single earlobe sensor in patients with critical illness or sleep apnea

OBJECTIVES: The purpose of the study was to evaluate a novel, combined sensor for transcutaneous monitoring of arterial oxygen saturation and carbon dioxide tension. DESIGN: The new monitoring technique was compared to established reference methods. SETTING: ICU and sleep laboratory of a university hospital. PATIENTS: Eighteen critically ill adult patients with acute respiratory failure or heart failure, and 12 patients with sleep apnea (mean [+/- SD] apnea/hypopnea index, 43 +/- 24 events per hour). MEASUREMENTS: Continuous measurements were performed over several hours by the novel heated (temperature, 42 degrees C) earlobe sensor (TOSCA; Linde Medical Sensors; Basel, Switzerland), incorporating electrochemical and optical elements for carbon dioxide measurement (PtcCO2) and pulse oximetry (SpO2), respectively. The data were compared to the results of repeated arterial blood gas analyses in critically ill patients and to simultaneous nocturnal pulse oximetry performed with different devices with earlobe or finger sensors in sleep apnea patients. RESULTS: In critically ill patients, the mean difference and limits of agreement (bias +/- 2 SDs) of transcutaneous PtcCO2 vs arterial PaCO2 were 3 +/- 7 mm Hg; the corresponding values for changes in PtcCO2 vs PaCO2 were 1 +/- 6 mm Hg. The bias +/- 2 SDs for pulse oximetric SpO2 vs arterial oxygen saturation (SaO2) were 1 +/- 4%. In sleep apnea patients, the combined earlobe sensor identified more transient oxygen desaturations, and the rate of change in oxygen saturation during events was greater compared to those with other tested pulse oximeters, indicating a faster response. CONCLUSIONS: Due to its ability to accurately assess both ventilation and oxygenation by a single transcutaneous sensor, the described noninvasive monitoring technique is a valuable tool for respiratory monitoring with potential applications in critical care and sleep medicine.     

Health and functional outcomes and health care utilization of persons with dementia in residential care and assisted living facilities: comparison with nursing homes

PURPOSE: This study compares health and functional outcomes and health care utilization of persons with dementia residing in residential care/assisted living (RC/AL) facilities and nursing homes. DESIGN AND METHODS: The study uses data from a longitudinal cohort study of 1,252 residents with dementia in 106 RC/AL facilities and 40 nursing homes in four states. RESULTS: Rates of mortality; new or worsening morbidity; and change in activities of daily living, cognition, behavioral problems, depressive symptoms, social function, and withdrawal did not differ between the two settings. However, because of death or transfer, only about one half of the persons with mild dementia and one third of those with moderate to severe dementia remained in RC/AL facilities 1 year after enrollment. In addition, hospitalization rates were greater among individuals with mild dementia in RC/AL facilities, largely because of a medically unstable subgroup with high nursing-home-transfer rates. IMPLICATIONS: Many persons with dementia can be served equally well in either setting; however, those with major medical care needs may benefit from nursing home residence.     

Über den Glykogengehalt in Mundhöhlencarcinomen

Zusammenfassung Im Rahmen einer größeren Untersuchung über die Möglichkeiten einer Früherkennung bösartiger Tumoren in der Mundhöhle werden 22 verschiedene Mundhöhlencarcinome auf ihren Gehalt an Glykogen untersucht. Dabei ergibt sich gegenüber den Carcinomen der Portio uteri einrelativ hoher Prozentsatz glykogenhaltiger Carcinome. Vergleichsweise werden daneben die Glykogenverhältnisse der normalen menschlichen Mundschleimhaut an 432 Mundschleimhautexcisionen lebender Patienten histochemisch untersucht und ein unterschiedlicher Glykogengehalt in den einzelnen Mundhöhlenregionen aufgedeckt. Innerhallb der Epithelschichten bleibt das Stratum germinativum stets glykogenfrei. Vergleichende Untersuchungen an der glykogenfreien Mundschleimhaut von Ratten und Kaninchen konnten nachweisen, daß Teilungszellen zur Glykogensynthese nicht in der Lage sind. Zur Klärung der Frage, ob der Glykogengehalt innerhalb der Mundschleimhaut dem Insulin-Adrenalin-Regulator unterliegt, wurden darüber hinaus die Mundschleimhautverhältnisse mittels der Schillerschen Jodlösung an 1661 Diabetikern geprüft und die Mundschleimhautexcisionen von 32 Diabetikern histochemisch ausgewertet und zum jeweiligen Blutzuckerspiegel in Relation gesetzt. Die Ergebnisse sprechen dafür, daß der Glykogengehalt der Mundschleimhaut nicht vom Insulinspiegel abhängt. Da sich für Phosphorylierungsvorgänge Anhaltspunkte nicht ergaben, wird das Glykogen der Mundschleimhaut und der Mundhöhlencarcinome als Stapelungsglykogen angesprochen.     

Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response

Gliomas attract brain‐resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro‐invasive cells. M‐CSF (macrophage colony‐stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM‐CSF (granulocyte–macrophage colony‐stimulating factor encoded by the CSF2 gene) but not M‐CSF when compared to normal astrocytes. Knockdown of GM‐CSF in GL261 glioma cells strongly reduced microglia‐dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1⁺ cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM‐CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro‐invasive activation in GM‐CSF‐depleted gliomas. Deficiency of M‐CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1⁺ cells, but impaired accumulation of Iba1⁺ cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and in response to injury. The expression of CSF2 (but not CSF1) was highly up‐regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM‐CSF triggers and drives the alternative activation of tumour‐infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The role of NF-κB and Smac/DIABLO proteins in the treatment response and survival of acute myeloid leukemia patients

IntroductionThe misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).Material and methodsThe aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.ResultsExpression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS.ConclusionsLower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.     

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10⁻⁴. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.