Functional changes in neutrophils and psychoneuroendocrine responses during 105 days of confinement.

The innate immune system as one key element of immunity and a prerequisite for an adequate host defense is of emerging interest in space research to ensure crew health and thus mission success. In ground-based studies, spaceflight-associated specifics such as confinement caused altered immune functions paralleled by changes in stress hormone levels. In this study, six men were confined for 105 days to a space module of ~500 m(3) mimicking conditions of a long-term space mission. Psychic stress was surveyed by different questionnaires. Blood, saliva, and urine samples were taken before, during, and after confinement to determine quantitative and qualitative immune responses by analyzing enumerative assays and quantifying microbicide and phagocytic functions. Additionally, expression and shedding of L-selectin (CD62L) on granulocytes and different plasma cytokine levels were measured. Cortisol and catecholamine levels were analyzed in saliva and urine. Psychic stress or an activation of the psychoneuroendocrine system could not be testified. White blood cell counts were not significantly altered, but innate immune functions showed increased cytotoxic and reduced microbicide capabilities. Furthermore, a significantly enhanced shedding of CD62L might be a hint at increased migratory capabilities. However, this was observed in the absence of any acute inflammatory state, and no rise in plasma cytokine levels was detected. In summary, confinement for 105 days caused changes in innate immune functions. Whether these changes result from an alert immune state in preparation for further immune challenges or from a normal adaptive process during confinement remains to be clarified in future research.

520-d Isolation and confinement simulating a flight to Mars reveals heightened immune responses and alterations of leukocyte phenotype.

During interplanetary exploration, chronic stress caused by long term isolation and confinement in the spacecraft is one of the major concerns of physical and psychological health of space travelers. And for human on Earth, more and more people live in an isolated condition, which has become a common social problem in modern western society. Collective evidences have indicated prolonged chronic stress could bring big influence to human immune function, which may lead to a variety of health problems. However, to what extent long-term isolation can affect the immune system still remains largely unknow. A simulated 520-d Mars mission provided an extraordinary chance to study the effect of prolonged isolation. Six healthy males participated in this mission and their active neuroendocrine and immune conditions were studied with saliva and blood samples from all participants on chosen time points during the isolation period. As a typical neuroendocrine parameter, stress hormone cortisol was measured in the morning saliva samples. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. Using an ex vivo viral infection simulation assay we assessed the immune response changes characterized by the ability to produce representative endogenous pro-inflammatory cytokines. The results of this study revealed elevated cortisol levels, increased lymphocyte amount and heightened immune responses, suggesting that prolonged isolation acting as chronic stressors are able to trigger leukocyte phenotype changes and poorly controlled immune responses.

Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.

BACKGROUND: In end-stage renal disease patients, the incidence of both infections and malignancies is increased leading to a higher incidence of peripheral lymphadenopathy. In the present work we describe a rare but probably underdiagnosed cause for enlarged lymph nodes in uremic patients. PATIENT: A 43-year-old male patient was admitted to our hospital with inguinal lymphadenopathy and pruritus. He turned out to be uremic due to focal segmental glomerulosclerosis (creatinine 4.5 mg/dl, MDRD creatinine clearance 12 ml/min). FINDINGS: Sonography revealed enlarged lymph nodes (up to 4 cm) with intact corticohilar border differentiation. After extirpation of an inguinal lymph node, histological examination established the diagnosis of dermatopathic lymphadenopathy. T cell lymphoma was excluded by PCR for T cell receptor-gamma rearrangements and subsequent GeneScan analysis. Intravenous fluid supplementation with subsequent decline of creatinine, UVB treatment, clemastine, and topical use of emollients led to a relief of the uremic pruritus and the lymph nodes' size normalized within 8 weeks. CONCLUSION: Dermatopathic lymphadenopathy refers to the reactive condition seen in lymph nodes that drain areas with disruption of the skin integrity, e.g. due to scratch marks. The present case report describes dermatopathic lymphadenopathy as a harmless cause of enlarged lymph nodes in uremic pruritus for the first time. This entity should be considered in the differential diagnosis of peripheral lymphadenopathy of unknown origin in patients with renal failure.

Drug therapy for hypertension in hemodialysis patients.

Hypertension in chronic hemodialysis patients is very common, and associated with cardiovascular morbidity and mortality. On the other hand, normalization of blood pressure in this patient population results in improvement of survival in the long-term. Drug therapy for hypertension in hemodialysis patients includes mainly angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta-blockers and diuretics, but guidelines for the use of specific classes of antihypertensive medications do not exist for end-stage renal disease (ESRD) patients on maintenance hemodialysis treatment. In survival analyses, some studies are in favour for the ACE inhibitors, other studies report reduced risk of cardiovascular mortality by using calcium channel blockers. Beta blockers seem to be ideal antihypertensive agents, since sympathetic nerve activity is inappropriately increased in ESRD patients. Most studies indicate that hypertension control is still not adequate in the majority of chronic hemodialysis patients. Randomized, controlled clinical trials are needed to determine the most advantageous antihypertensive agent(s) to use in ESRD patients on chronic hemodialysis therapy.

Neutrophil activation in acute renal failure and sepsis.

Neutrophils are activated during sepsis. To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis. During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis. Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis. There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone. Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis. Cellulose-containing dialysis membranes introduce a further activation of neutrophils.

Animal model for chronic-abscess-forming peritonitis: histology and microbiology.

Clinical experience gives evidence of the increasing importance of chronic-abscess-forming peritonitis with a general physical impairment in spite of a well-controlled abdominal situation. The number of unsolved problems led us to develop a standardized and reproducible experimental animal model, using Wistar rats. We induced peritonitis by intraperitoneal injection of a mixture containing a capsulated strain of Bacteroides fragilis and DEV agar. The histologic changes in the parietal and visceral peritoneum, lymphnodes and liver were recorded in the course of the disease. The data largely correlate with those recorded in human peritonitis. Bacteriologic examinations gave evidence of bacteria passing through the intestinal wall into the abdomen. This is the first model for peritonitis which is defined by its histological and bacteriological course. It enables one to examine pathophysiological problems and the consequences of harm and stress for the course of the disease.

[Vascular spasms in microsurgery]. / Gefässspasmen in der Mikrochirurgie.

Human arteries and veins contract with hypoxia and deprivation of substrate provoked by increasing calcium inflow into the cell and reduced energy. Such spasm may be eliminated by phosphoenolpyruvate which loads up the cell's energy, blocking glycogen reduction at the same time. Reperfusion will then guarantee a sufficient energy stroke. Therapy should pursue the following steps: 1. Phosphoenolpyruvate infusion (1 X 10(-6) up to 1 X 10(-3) gm/ml in tyrodes solution pH 7.3) into the arterial branch, proximal and distal to the injury. 2. Subsequent treatment with vasodilating drugs and rheologically active substances. 3. Failed therapy after more than three hours warm ischemia could be due to autolytic processes and requires resection of the affected vessel. 4. The imbalance of the thrombolytic system with the so-called no reflow phenomenon could be due to a plasminogen activator's inhibitor released during hypoxia. Such cases may reasonably be treated by urokinase or by streptokinase plasminogen complex.

Intraarterial prostaglandine E1 in arterial occlusive disease (AOD) stages III and IV.

Our physical, chemical and clinical findings - especially lactate, night pain and peripheral blood flow - have shown that in most cases of AOD stages III and IV, intraarterial infusions with prostaglandine E1 largely improved the peripheral situation. PGE1 seems to meliorate the blood flow - causing better oxygen supply - and to inhibit thrombocyte aggregation. An improvement of the clinical situation will be the result. In most cases a differentiation between responders and non-responders is possible but, on the other hand, it is not possible, however, to give a safe forecast of the success of this treatment in the individual patient.

Carbohydrate metabolism of dog skeletal muscle during immobilization.

The effect of immobilization and the following mobilization on muscle carbohydrate metabolism was investigated in dogs. Total carbohydrate and glycogen content of skeletal muscle fell during immobilization. The glycogen-degrading enzyme phosphorylase was activated 1 week after immobilization (a/b ratio 40.6 +/- 7.6 vs. 27.1 +/- 6.5%). Thereafter, the enzyme activity decreased and remained significantly lowered even 2 weeks after the following mobilization. In contrast, muscle glucose and lactate concentration were unchanged. Our data indicates glycogen breakdown of dog skeletal muscle during immobilization. Even after 2 weeks of mobilization muscle glycogen content has not reached glycogen values of the untreated dogs.

Plasma proteinases, proteinase inhibitors and other selective plasma proteins following aortofemoral bypass operation.

Monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins was evaluated in patients undergoing Y-graft aortofemoral bypass operation. Fast-reacting acute-phase proteins (C-reactive protein, antichymotrypsin, alpha 1-acid glycoprotein) and slow-reacting proteins (haptoglobin, alpha 1-antitrypsin) increased significantly 48-120 h after operation. By contrast, no significant increase was found between plasma ceruloplasmin levels before clamping and after declamping. Activity and concentration of alpha 2-macroglobulin decreased postoperatively and remained significantly lowered throughout the observation period. Plasma levels of granulocyte elastase were elevated significantly 1 h after declamping, whereas trypsin-binding capacity decreased immediately after the release of the clamp. Aprotinin pretreatment caused higher trypsin-binding capacity of the plasma, significantly lower 'unspecific' proteolytic (azocasein-hydrolyzing) activity and significantly lower non-TCA precipitable low molecular weight plasma protein concentration. Our results confirm the data of several authors that monitoring of plasma proteinases, proteinase inhibitors and other selective plasma proteins may be helpful in evaluating surgical patients postoperatively.

Effect of tourniquet ischaemia on carbohydrate metabolism of dog skeletal muscle.

Metabolic changes in blood and skeletal muscle of dogs before, during and after tourniquet ischaemia were investigated to obtain further information on cellular metabolic abnormalities and restitution during and following long-lasting blood flow interruptions. Total carbohydrate and glycogen contents in the muscle tissue fell during ischaemia and remained significantly decreased even 1 h after recirculation due to inhibition of glycogen synthetase activity. Muscle glucose concentration remained stable during ischaemia and was significantly elevated 1 h after tourniquet release. In contrast, muscle lactate concentration was elevated during ischaemia and normal after recirculation. Blood lactate, pyruvate and serum inorganic phosphate concentrations increased markedly after tourniquet release and were still significantly elevated 1 h after recirculation, whereas ketone bodies and citric acid cycle intermediates remained unchanged. Tourniquet ischaemia had no effect on muscle phosphate concentration or on the activities of proteases, protease inhibitors or hydrolases in the blood. Nevertheless, our results clearly indicate metabolic abnormalities in the blood and skeletal muscle during 5 h of tourniquet ischaemia and even after 1 h of recirculation.

[Nonocclusive ischemic enteropathy--a rare cause of ileus]. / Die nichtocclusive ischämische Enteropathie--als seltene Ursache eines Ileuszustandes.

The cause for a nonocclusive ischemic enteropathy seems to be a low cardiac output syndrome. There are often signs of a paralytic intestinal obstruction. Parameters of the blood chemistry offer no conclusive data. The angiogram of the mesenteric vessels demonstrates extensive arterial vasoconstriction as well as an obstructed venous outflow. Experimental findings disclose that this venous obstruction may be a result of an ischemic contracture in the course of a low flow state. This rigor initiates finally a thrombosis of the venoles. The rigor can be effectually mastered by energy-rich compounds.