[V. A. C. INSTILL® therapy - new option in septic thoracic surgery]. / V. A. C.-INSTILL®-Therapie - neue Wege in der septischen Thoraxchirurgie.

BACKGROUND: The V. A. C. INSTILL® therapy is an innovative process for treating chronic wounds that are not optimally accessible to a systemic antibiotic therapy or infected with multi-resistant pathogens. We report on our first experience and applications of V. A. C. INSTILL® therapy in the field of septic thoracic surgery. MATERIALS AND METHODS: V. A. C. INSTILL therapy was used in 11 cases between 11/2009 and 01/2012. Three patients had sternum osteomyelitis (2 MRSA, 1 Finegoldia magna). In 3 patients chronic pleural empyema after lobectomy (1 Streptococcus viridans, 1 mixed infection with MRSA among others) and after pneumectomy (1 MRSA) were detected. In 2 cases there was an acute pleural empyema with extensive phlegmona in the region of the thoracic soft tissues (2 streptococci). In 1 patient a chronic pleural empyema with MRSA infection was treated. Septic arthritis of the sternoclavicular joint with joint destruction and extensive phlegmona in the region of the cervical soft tissues (1 Streptococcus pneumoniae, 1 Staphylococcus aureus) was treated in 2 patients. In all cases instillation of the wound was performed with Lavasept 0.2 %. Swabs of the wound were taken before starting and after ending V. A. C. INSTILL® therapy as well as before wound closure. RESULTS: Mean patient age was 48.8 ± 18.9 years. V. A. C. INSTILL® therapy was performed for 6.5 ± 1.7 days. Instillation time amounted to 21.7 ± 5.7 s. The duration of action was standardised at 18 min in all cases. In 2 cases (1 MESA, 1 finegoldia) the V. A. C. INSTILL® therapy was repeated. In 10 patients a sterile wound status was achieved before secondary wound closure. All wounds underwent secondary closure without recurrence. CONCLUSIONS: Chronic osteomyelitis with MRSA infections as well as chronically infected residual cavities after empyema surgery and extensive phlegmona are possible indications for V. A. C. INSTILL® therapy in order to help eradicating the infection as quickly and as completely as possible.

[Consultation or liaison psychotherapy service--what difference does it make for an outpatient pain clinic?]. / Psychosomatischer Konsil-oder Liaisondienst in einer Schmerzambulanz Was verändert sich?

OBJECTIVES: Even if the effectiveness of psychotherapy emphasising a cognitive behavioral approach is clearly shown by randomised controlled trials, it is difficult to motivate chronic pain patients to use this type of treatment. We compared the effectiveness of consultation and liaison models of co-operation between an outpatient pain clinic and a psychosomatic department in creating motivation to psychotherapy. METHODS: In a retrospective design we collected data of all patients seen in the pain clinic during two periods of 6 months before ( N=165) and after ( N=277) changing from a consultation to a liaison model. Clinical data were documented by the MASK system (Hildebrandt u. Pfingsten 1993). Depression was screened using a depression scale (vgl. Zerssen 1973), somatic complaints by listing of complaints (vgl. Zerssen u. Koeller 1976) and two short screening questionnaires. RESULTS: In the liaison model diagnostic sessions with the consulting psychotherapist were significantly more often recommended by physicians from anaesthesia departments (25.6% vs 13.9%; p<0.01) and accepted by patients (63.3 vs 30.4%; p<0.01). In both systems 80% of the patients accepted the suggested psychotherapy. After changing to the liaison type of co-operation, there was a significant decrease in the prescription of opioid and benzodiazepine drugs. CONCLUSIONS: The liaison model of co-operation was significantly more effective to enhance physician's and patient's motivation for a psychosomatic approach to pain treatment. Psychotherapy is better accepted by patients suffering from chronic pain if it is offered in a multidisciplinary context and in the familiar surroundings of the pain clinic.

The matrix metalloproteinase inhibitor batimastat inhibits the lung colonisation of orthotopically implanted malignant pancreatic tumor cells in SCID mice.

AIM OF STUDY: In this study, we investigated the effect of the matrix metalloproteinase inhibitor batimastat on the lung colonisation of orthotopically implanted malignant pancreatic tumor cells in SCID mice. MATERIAL AND METHODS: Following intraperitoneal anaesthesia, 10(6) Panc-TU-1 cells were orthotopically implanted in the head of the pancreas in 20 SCID mice. Seven days later, treatment of 10 of these mice with an intraperitoneal injection of batimastat (30 mg/kg body weight) was begun and continued for 14 days. Of the mice in the untreated control group, 3 were sacrificed and examined after 7 days, a further 3 after 14 days and the remainder together with the group that had been treated after 21 days. RESULTS: Tumor growth was clearly visible between the 14th. and the 21st. postoperative day. The orthotopically implanted tumor cells metastasized between the 2nd. and 3rd. postoperative week in the lung. In the control group, a diffuse metastasis of the lung was observed, but in the group of treated mice no lung metastases were found. CONCLUSION: In this mouse model, a clear reduction and inhibition of lung metastases from orthotopically implanted pancreatic tumor cells was achieved by treatment with the matrix metalloproteinase inhibitor batimastat.

Bronchopleural fistula in the surgery of non-small cell lung cancer: incidence, risk factors, and management.

BACKGROUND: The incidence of a bronchopleural fistula (BPF) as a major complication after non-small cell lung carcinoma (NSCLC) surgery has decreased in recent years, due to new surgical refinements and a better understanding of the bronchial healing process. We reviewed our most recent experience with BPFs and tried to determine methods which may effectively reduce its occurrence. METHODS: Data on 490 patients with lung resections for NSCLC over a period from 1990 to 1999 were retrospectively reviewed. Details regarding surgery and the subsequent treatment were carefully reviewed. Particular attention was paid to factors possibly affecting the occurrence of BPFs: the technique of the initial bronchial closure, previous radiation and/or chemotherapy, need for postoperative ventilation and presence of residual carcinomatous tissue at the bronchial suture line. Information about age, sex, clinical diagnosis, associated conditions, TNM stage, period between primary operation and rethoracotomy and postoperative outcome was also recorded. RESULTS: The overall BPF incidence was 4.4% (22/490). There were 21 (95.5%) males and 1 (4.5%) female, mean age was 57.8 years. BPFs occurred after pneumonectomy in 12 (54.6%), after lobectomy in 9 (40.9%) patients and after sleeve resections in 1 (4.5%) patient. Mortality rate was 27.2% (6/22). Right-sided pneumonectomy and postoperative mechanical ventilation were identified as risk factors for BPFs (p<0.05). Initial chest re-exploration was performed in 20 (90.9%) patients. After debridement, the bronchial stump was reclosed by hand suture in 10 (45.4%) patients. All 10 (45.4%) patients with a post-lobectomy- and sleeve resection BPF necessitated completion surgery. The BPF was additionally covered with a vascularized flap in 20 (90.9%) patients. In 2 (9%) patients with small BPFs and poor overall condition the initial treatment was endoscopic. In both the fistula persisted and the stump had to be surgically resutured. CONCLUSIONS: A BPF remains a major complication in the surgery of NSCLC because of its high mortality and morbidity rate. A BPF is more common after right-sided pneumonectomy and is frequently associated with postoperative mechanical ventilation. The management varies according to the initial type of surgery, the size of the BPF, the overall patient condition and that of the remaining lung. Endoscopic treatment is reserved only for small fistulas associated with poor general condition.

Hirsutism-skeletal dysplasia-mental retardation syndrome with abnormal face and a uric acid metabolism disorder.

We report on a German boy, born to nonconsanguineous parents, with an apparently new combination of multiple congenital anomalies including extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pedes excavati with claw-toes, an abnormal face, and mental retardation. Additionally the boy manifests a disorder of uric acid metabolism. This sporadic case may represent a new syndrome due to a fresh autosomal or X-linked mutation, or chance-isolated case due to segregation of an autosomal recessive gene.

Element concentrations (selenium, copper, zinc, iron, magnesium, potassium, phosphorous) in heart tissue of patients with coronary heart disease correlated with physiological parameters of the heart.

The element concentrations (Cu, Zn, Se, Fe, K, Mg, P) of heart tissue taken from patients with coronary heart disease during bypass surgery were measured and related to physiological parameters of the heart. There was no relationship between the element concentrations and the number of vessels stenosed, the occurrence of myocardial infarction or classification according to the NYHA. When the element concentrations of the heart were related with parameters characterizing cardiac output, such as ejection fraction and cardiac index, positive statistically significant correlations were found for selenium, iron, copper, zinc and phosphorus.

Trace element concentrations (Cu, Zn, Fe) in sera from patients with dilated cardiomyopathy.

The trace element concentrations (Cu, Zn, Fe) in sera from patients with dilated cardiomyopathy are reported. Patients with dilated cardiomyopathy have high copper and low zinc concentrations in serum compared to healthy controls. The trace element concentration profile is different from that of other heart diseases like myocardial infarction and coronary heart disease. The copper concentration in serum shows a highly significant inverse relationship with the ejection fraction and the cardiac index. Pathophysiological processes which raise the copper concentration in serum may influence the ejection fraction and the cardiac index.

Increase in proto-oncogene raf expression precedes differentiation induction in different clonal rhabdomyosarcoma subpopulations.

Three clonal rat rhabdomyosarcoma subpopulations (A, B, C) with a block of differentiation at different levels of rhabdomyogenesis were exposed to the differentiation inducers retinoic acid (RA), N-methylformamide (NMF) and sodium butyrate (NaBut). Since an increased expression of c-raf and c-fos had recently been demonstrated for subpopulation C after exposure to RA and NMF (1), the mRNA expression of c-raf, c-fos and retinoic acid receptor (RAR) alpha, beta and gamma was compared in all three subpopulations. After exposure to RA, NMF or NaBut, subpopulation C exhibited a significant (p = 0.0001) increase in creatine kinase (CK) activity and in morphological differentiation. In subpopulation B, the response was confined to a significant (p = 0.0001) increase in creatine kinase activity, whereas subpopulation A proved to be differentiation-refractory. On the molecular level, a uniform increase in c-raf expression became evident in all three subpopulations after 6 to 12 hours, persisting at an elevated level throughout the observation period of 120 hours. In contrast, the pattern of c-fos expression observed after exposure to RA, NMF or NaBut was heterogeneous. Expression of RAR alpha and gamma was detected in all subpopulations, whereas RAR beta mRNA was not expressed. Summarizing our results, the uniform pattern of c-raf expression might suggest a participation of c-raf in differentiation signal transduction. Since the three subpopulations differ markedly in their degree of differentiation, the block of differentiation characteristic for each subpopulation supposedly becomes effective only after the action of the c-raf gene product.

Enhanced expression of the proto-oncogenes fos and raf in the rhabdomyosarcoma cell line BA-HAN-1C after differentiation induction with retinoic acid and N-methylformamide.

BA-HAN-IC is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated post-mitotic myotubes. Exposure of BA-HAN-IC cells to retinoic acid (RA) or N-methylformamide (NMF) resulted in a significant inhibition of proliferation (p less than 0.001) and in cellular differentiation, as evidenced by a significant increase in the creatine kinase (CK) activity (p less than 0.05) and the number of terminally differentiated post-mitotic myotubes (p less than 0.001). Furthermore, between 5% (NMF) and 30% (RA) of the mononuclear tumor cells exhibited ultrastructural features of rhabdomyogenic differentiation, not observed in their mononuclear counterparts under standard growth conditions. Although BA-HAN-IC cells responded to both inducers of differentiation, differences in time course and magnitude of both increase of differentiation and growth inhibition were observed. These effects of RA and NMF were preceded by a marked enhancement of c-raf expression which became evident 6 and 12 hr after exposure to RA and NMF, respectively, and which persisted throughout the observation period of 5 days. Furthermore, a transient expression of c-fos could be observed 15 and 30 min after exposure to RA. Our results suggest that c-raf expression might be implicated in the differentiation process of BA-HAN-IC tumor cells.

The renal excretion of selenium.

The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7 +/- 4.2 micrograms Se/d and men 19.0 +/- 9.0 micrograms Se/d. The daily selenium excretion per gram creatinine is 13.5 +/- 3.8 micrograms Se/g crea for women and 9.8 +/- 3.3 micrograms Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24 h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24 h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24 h selenium excretion is further influenced by the 24 h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.

Selenium and cardiovascular disease.

For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipid peroxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.

Uniform response of c-raf expression to differentiation induction and inhibition of proliferation in a rat rhabdomyosarcoma cell line.

The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. Both the induction of differentiation by retinoic acid (RA) and by sodium butyrate (NaBut), as well as the inhibition of proliferation by fetal calf serum (FCS)-depleted medium uniformly resulted in the same effects. There was a significant (p less than 0.001) inhibition of proliferation and induction of cellular differentiation, as evidenced by a significant (p less than 0.05) increase in creatine kinase activity. Furthermore, after exposure to RA-supplemented or FCS-depleted medium, a significant (p less than 0.001) increase in the number of myotube-like giant cells was observed. These effects were preceded by a uniform enhancement of c-raf mRNA expression, which became evident 6 h after exposure to RA, NaBut and FCS-depleted media. C-raf mRNA expression persisted at an elevated level throughout the observation period of 5 days after exposure to RA or NaBut, whereas the increased expression of c-raf mRNA observed after FCS-depletion declined near to the basal level after only 24 h. Furthermore, a transient c-fos mRNA expression was observed 15 and 30 min after exposure to RA-supplemented and FCS-depleted medium but not after exposure to NaBut. The present results suggest a possible role of c-raf in the regulation of differentiation and proliferation of this cell line. Since all our experiments with RA, NaBut and FCS-depletion resulted in an early peak of c-raf mRNA expression, it is suggested that this early peak may be sufficient to trigger events crucial for differentiation and proliferation of BA-HAN-1C tumor cells.

Concentrations of some trace elements (Se, Zn, Cu, Fe, Mg, K) in blood and heart tissue of patients with coronary heart disease.

We measured Se, Zn, Fe, Cu, Mg, and K in blood and heart tissue of patients with coronary heart disease. Such patients have subnormal selenium concentrations in serum, whole blood, and (calculated per gram of hemoglobin) erythrocytes. Concentrations of zinc and copper in serum were also subnormal in these patients. Heart tissue collected from these patients during bypass surgery was analyzed for Se, Zn, Fe, Cu, Mg, and K; results are expressed in terms of wet weight and in relation to nitrogen and phosphorus content. Concentrations of these elements in blood are correlated with those in heart tissue. Selenium concentrations in serum correlated positively with those in tissue but not with those in erythrocytes. We found no association between concentrations of zinc, iron, copper, magnesium, and potassium in serum and the corresponding concentrations in heart tissue. There was a moderately positive correlation between the concentration of ferritin in serum and that of iron in tissue. We conclude that the turnover rate for selenium in tissue is similar to that in serum but greater than that for erythrocyte selenium. The concentrations of these six elements in heart tissue are partly correlated with the ejection fraction of the left ventricle.

Selenium metabolism and supplementation in patients with muscular dystrophy.

We studied selenium metabolism in patients with Duchenne muscular dystrophy and in contrast to previous reports found no significant abnormalities in these patients. Supplementation of muscular dystrophy patients and control subjects with sodium selenite (1 mg selenium/day) induced a variable rise in the activity of the selenium-dependent enzyme glutathione peroxidase in plasma and red cells, but no significant change in muscle glutathione peroxidase activities. There was no effect of selenium supplementation on disease activity in the patients with muscular dystrophy. Thiobarbituric acid-reacting substances (an index of free radical-mediated lipid peroxidation) were elevated in the muscle of patients with Duchenne muscular dystrophy in contrast to patients with other forms of muscular dystrophy and control subjects. This elevation was unaffected by selenium supplementation.

The daily dietary selenium intake of West German adults.

The selenium content of food consumed in the Federal Republic of Germany (FRG) was determined for the estimation of the dietary selenium intake of West German adults. The daily dietary selenium intake of men is 47 micrograms (micrograms) and that of women 38 micrograms, corresponding to 0.67 microgram/kg body weight per day for both men and women. Animal protein is the main source of dietary selenium, accounting for 65.5% of the total selenium intake. Pork contributes 25.1% to the total Se intake, reflecting the current consumption and the selenium supplementation of feedstock rather than the availability of selenium from natural dietary sources. The selenium intake of adults in West Germany is only slightly higher than in New Zealand, Finland, and Italy, nearly equal to that in Belgium and France, and distinctly lower than in Great Britain, the USA, Canada, and Japan.

The organ distribution of selenium in German adults.

The selenium concentrations were determined in liver, kidney, skeletal muscle, heart, brain, prostate, testis, bile, lung, and spleen of German traffic accident victims. In addition, the nitrogen and phosphorus contents were determined in the same organs and tissues. On a per-weight unit basis, the highest selenium concentration was found in kidney. However, this corresponds to only 4% of the total body selenium. Most of the whole body selenium (50%) is present in skeletal muscle, which thus appears to act as a selenium storage organ. However, there is also evidence that selenium is required for muscle function. In plasma and interstitial fluid, .450 mg of Se, or 7.5% of the total body selenium is present. A comparison of the organ Se concentrations of the German traffic accident victims with the selenium concentrations of the same human organs as reported in different countries indicates that the organ concentrations of West Germans are comparable to that of the population of New Zealand, a low-Se country, and significantly lower than that observed in the organs of American, Canadian, and especially Japanese subjects. The international comparison of the organ selenium concentrations also revealed that the selenium uptake of kidney is higher at low- and adequate dietary Se intakes and lower if the dietary Se supply is high, as is the case for Japanese subjects. Estimates of the daily excretion of selenium with the bile indicate that the amounts are three times higher than the daily urinary losses and in the same order of magnitude as the daily dietary selenium intakes. Enterohepatic reabsorption of selenium from the bile appears to be a significant mechanism of conserving dietary selenium and to maintain Se balance at comparatively low dietary Se intakes.

Correlations of blood selenium with hematological parameters in West German adults.

The serum selenium and the whole blood selenium of 72 healthy persons (47 women, 25 men) was determined. There exist sex specific differences of the whole blood selenium between men (98 +/- 19 micrograms Se/L) and women (89 +/- 17 micrograms Se/L). The serum selenium did not show sex specific differences, but sex specific differences are found if the total amount of extracellular selenium is calculated by correction of the serum selenium with the hematocrit. Women have more extra-cellular selenium/L whole blood (40 +/- 8 micrograms Se) than men (36 +/- 7 micrograms Se). Men have more intraerythrocyte selenium (cellular selenium = 67 +/- 14 micrograms Se) in one L whole blood than women (52 +/- 17 micrograms Se). There exist also sex specific differences if the cellular selenium is calculated/g hemoglobin (men .44 micrograms Se/g Hb, women .37 micrograms Se/Hb) or per erythrocyte (men 136.1 x 10(-19) g Se/Ery, women 113.9 x 10(-19) g Se/Ery). In the cellular compartment of one L whole blood on the average 1.56 times more selenium is present than in the extracellular compartment. Most of the intraerythrocyte selenium is hemoglobin bound (84%) and utmost 16% glutathione peroxidase associated. An erythrocyte contains about 3500 mol glutathione peroxidase, or, for every 80000 mol hemoglobin one mol glutathione peroxidase. A standard man needs about 2.5 micrograms selenium/d for the synthesis of the hemoglobin and the erythrocyte. The hematological parameters hemoglobin and the erythrocyte number are correlated with the cellular selenium and the ratio cellular selenium/extracellular selenium. Positive significant correlations are found that are best if a parabolic model is used to interpret the shape of the curves. From the shape of the best correlation lines it can be concluded that selenium may be beneficial for hemoglobin synthesis and erythropoesis. The extracellular selenium may have influence on the volume of the erythrocyte by protecting the outer erythrocyte membrane from lipid peroxidation. A method is reported based on the carbon furnace atomic absorption spectroscopy, which is able to determine without wet digestion selenium in whole blood.

Determination of apolipoprotein variants by isoelectric focusing in agarose.

Isoelectric focusing (IEF) of apolipoproteins is an important procedure for the isolation of apolipoprotein isoforms. In this paper we describe the use of agarose/urea as a focusing medium for IEF of apolipoproteins. This technique, which offers several advantages over the traditional polyacrylamide gel focusing, yields a further microheterogeneity of the known isoforms of apolipoproteins A-I and E. In addition, by subsequent immunoprecipitation, both specificity and sensitivity are enhanced. Using a monospecific antiserum against Apo A-I, a new minor isoform was detected at the basic end of the Apo A-I spectrum (pI 6.02) which has not yet been observed in normal plasma samples. Another advantage of this technique in combination with immunoprecipitation is the specific detection of Apo E phenotypes which is essential for the diagnosis of hyperlipoproteinemia type III.