Systemic lupus erythematosus in the light of the regulatory effects of galectin-1 on T-cell function.

Galectin-1 is an endogenous immunoregulatory lectin-type protein. Its most important effects are the inhibition of the differentiation and cytokine production of Th1 and Th17 cells, and the induction of apoptosis of activated T-cells. Galectin-1 has been identified as a key molecule in antitumor immune surveillance, and data are accumulating about the pathogenic role of its deficiency, and the beneficial effects of its administration in various autoimmune disease models. Initial animal and human studies strongly suggest deficiencies in both galectin-1 production and responsiveness in systemic lupus erythematosus (SLE) T-cells. Since lupus features widespread abnormalities in T-cell activation, differentiation and viability, in this review the authors wished to highlight potential points in T-cell signalling processes that may be influenced by galectin-1. These points include GM-1 ganglioside-mediated lipid raft aggregation, early activation signalling steps involving p56Lck, the exchange of the CD3 ζ-ZAP-70 to the FcRγ-Syk pathway, defective mitogen-activated protein kinase pathway activation, impaired regulatory T-cell function, the failure to suppress the activity of interleukin 17 (IL-17) producing T-cells, and decreased suppression of the PI3K-mTOR pathway by phosphatase and tensin homolog (PTEN). These findings place galectin-1 into the group of potential pathogenic molecules in SLE.

[What Makes Happy Doctors? Job Satisfaction of General Practitioners in Mecklenburg-Western Pomerania - a Representative Cross-sectional Study]. / Was macht Ärzte glücklich? Berufszufriedenheit von Hausärzten in Mecklenburg-Vorpommern - eine repräsentative Querschnittsstudie.

AIM: Studies provide evidence for the importance of general practitioners (GPs) job satisfaction for a secure and high quality health care provision. This study focuses on job satisfaction of GPs in Mecklenburg-Western Pomerania (MV), a rural area threatened by a lack of GPs. We investigate how satisfied GPs are with their job and which factors influence their job satisfaction. METHODS: All 1 133 GPs working in MV in December 2011 were asked to complete a 57-item-questionnaire. The response rate reached 50.1%. RESULTS: The sample is representative for GPs in MV. Levels of job satisfaction are high and correlate with age and sex: females and GPs below 50 years of age are more satisfied. Factors contributing to high job satisfaction include a good doctor-patient relationship, fair pay, and the variety of reasons for doctor-patient consultations in primary care. Although all GPs were dissatisfied with bureaucracy, this factor has little impact on GPs' overall job satisfaction. CONCLUSION: In light of the imminent lack of GPs, in future it will be important to improve factors that have been demonstrated to increase job satisfaction.

Hepatic effects of an open lung strategy and cardiac output restoration in an experimental lung injury.

BACKGROUND: Ventilation with high positive end-expiratory pressure (PEEP) can lead to liver dysfunction. We hypothesized that an open lung concept (OLC) using high PEEP impairs liver function and integrity dependent on the stabilization of cardiac output. METHODS: Juvenile female Pietrain pigs instrumented with flow probes around the common hepatic artery and portal vein, pulmonary and hepatic vein catheters underwent a lavage-induced lung injury. Ventilation was continued with a conventional approach (CON) using pre-defined combinations of PEEP and inspiratory oxygen fraction or with an OLC using PEEP set above the lower inflection point of the lung. Volume replacement with colloids was guided to maintain cardiac output in the CON(V+) and OLC(V+) groups or acceptable blood pressure and heart rate in the OLC(V-) group. Indocyanine green plasma disappearance rate (ICG-PDR), blood gases, liver-specific serum enzymes, bilirubin, hyaluronic acid and lactate were tested. Finally, liver tissue was examined for neutrophil accumulation, TUNEL staining, caspase-3 activity and heat shock protein 70 mRNA expression. RESULTS: Hepatic venous oxygen saturation was reduced to 18 + or - 16% in the OLC(V-) group, while portal venous blood flow decreased by 45%. ICG-PDR was not reduced and serum enzymes, bilirubin and lactate were not elevated. Liver cell apoptosis was negligible. Liver sinusoids in the OLC(V+) and OLC(V-) groups showed about two- and fourfold more granulocytes than the CON(V+) group. Heat shock protein 70 tended to be higher in the OLC(V-) group. CONCLUSIONS: Open lung ventilation elicited neutrophil infiltration, but no liver dysfunction even without the stabilization of cardiac output.

[Twenty years of experience with bariatric surgery in a general hospital]. / Entwicklung der Adipositaschirurgie am Krankenhaus der Maximalversorgung: Uber 20 Jahre Behandlungserfahrung.

BACKGROUND: Bariatric surgery has been performed since 1983 at the Bad Cannstatt Hospital near Stuttgart, Germany. The aim of this study was to investigate the development of bariatric surgery during the past 25 years. METHODS: Data were collected retrospectively. The parameters were number of surgical procedures, hospital stay, and postoperative complications. RESULTS: In the 25-year period 1,041 primary bariatric operations were performed. Open horizontal bypass and open vertical banded gastroplasty were performed initially. Starting in 2003 there was a change to laparoscopic procedures (gastric banding and Roux-en-Y bypass). The mean hospital stays were 14.7+/-5.1 days for open procedures and 6.7+/-4.2 days for laparoscopic methods, with 30-day mortalities of 0.8% and 0.0% and short-term complications at 16.9% and 7.8%, respectively. CONCLUSIONS: Perioperative complications and hospital stay were reduced by performing laparoscopic bariatric surgery. Our study emphasizes the advantages of the laparoscopic procedures which are standard at our hospital and fit in with the remaining operations in a department of visceral surgery.

Eighty-four potential second-look operations based on sequential carcinoembryonic antigen determinations and clinical investigations in patients with recurrent gastrointestinal cancer.

In our study of patients with resected primary gastrointestinal cancer, slope analysis of the post-operatively increasing carcinoembryonic antigen time courses signaled relapse in about 80 percent of the patients up to 12 months before positive clinical diagnosis. In 29 patients, clinical confirmation of the relapse could be obtained only after second-look surgery. Slope analysis generally differentiated localized from metastatic disease and therefore also predicted the site of relapse. A first evaluation of 84 patients with potential cases of second-look operations provided evidence for a significant increase in survival. Recently, the evaluation of individual carcinoembryonic antigen doubling times was used to derive an individual prognosis since doubling times strongly correlated with the survival of untreated patients. On this basis, it was clearly possible to show the benefit of second-look operation, since patients with resectable recurrences exhibited longer survival times compared with patients with similar carcinoembryonic antigen doubling times without treatment. Moreover, the introduction of monoclonal antibodies with increased specificity for malignant states, has facilitated the selection of patients for second-look operation because unspecific carcinoembryonic antigen elevations are less frequent and recurrent disease can be predicted more reliably due to the higher carcinoembryonic antigen increments associated with malignant growth.

Intermediate pyrolysis of biomass energy pellets for producing sustainable liquid, gaseous and solid fuels.

This work describes the use of intermediate pyrolysis system to produce liquid, gaseous and solid fuels from pelletised wood and barley straw feedstock. Experiments were conducted in a pilot-scale system and all products were collected and analysed. The liquid products were separated into an aqueous phase and an organic phase (pyrolysis oil) under gravity. The oil yields were 34.1 wt.% and 12.0 wt.% for wood and barley straw, respectively. Analysis found that both oils were rich in heterocyclic and phenolic compounds and have heating values over 24 MJ/kg. The yields of char for both feedstocks were found to be about 30 wt.%, with heating values similar to that of typical sub-bituminous class coal. Gas yields were calculated to be approximately 20 wt.%. Studies showed that both gases had heating values similar to that of downdraft gasification producer gas. Analysis on product energy yields indicated the process efficiency was about 75%.

[Obesity surgery: the refusal rate of health care cost reimbursement despite expert opinion]. / Adipositaschirurgie: Ablehnung der Kostenübernahme trotz ärztlicher Gutachten.

BACKGROUND AND OBJECTIVE: Surgery is an effective method to treat patients with morbid obesity. However health insurance companies frequently refuse to cover the costs for the procedure despite an existing DRG-code for this operation. Individual medical expertise are necessary to receive reimbursement. In the present study the acceptance of medical expertise to receive cost coverage was analysed in our patients of the years 2000-2003 eligible for obesity surgery. PATIENTS AND METHODS: 617 medical expertise of patients eligible for obesity surgery in our hospital were reviewed and the acceptance rate was evaluated. Parameters such as body mass index, personal medical history, diets, comorbidity and prognosis were included. Expertise were submitted to the health care insurance companies and in case of acceptance the operation was performed. RESULTS: The average age of our patients was 39.1 +/- 11.2 years, 72.1% were female, 27.9% male. The average BMI was 47.5 +/- 7.4 kg/m2. There was a high incidence of comorbidity in these patients (58.7% arterial hypertension, 38.6% diabetes mellitus, 95.8% dyspnoea, 96.1% arthropathy, 89.0% psychosocial disorders). The difference between accepted and non-accepted regarding these secondary complications was not significant. 209 patients (33.8%) were operated. 14 patients of these paid the costs themselves. Only in 195 cases (31.6%) the health care insurance company covered the costs for the operation. CONCLUSION: The high number of refusals of medical expertise is not justified in view of the strict criteria for indication, the high frequency of comorbidity and the good results after the operation.

Prognostic value of preoperative serum CEA level compared to clinical staging: II. Stomach cancer.

In a clinical investigation of postoperative survival after primary surgery for stomach cancer, 390 patients were registered since 1974. The potential prognostic parameters examined within the first days of hospitalization for primary resection included age of the patients, operability, tumour extension (TNM classification) and tumour stages I-IV (UICC). Statistical treatment of the data revealed that each of the clinical parameters covers critical ranges associated with highly significant differences in patient survival. The preoperative serum CEA concentration exhibited prognostic significance in addition to the criteria of operability and tumour extension. In selected subgroups of patients with distinct resectability and tumour extension, ranges of preoperative CEA concentration could be specified which were associated with statistically significant differences in the patient survival. The results indicate that the preoperative serum CEA level can be an independent prognostic parameter in stomach cancer.

Doubling time of circulating cea and its relation to survival of patients with recurrent colorectal cancer.

In a retrospective study the postoperative time courses of CEA in colorectal cancer patients with recurrent disease were analysed. In 87/114 cases with increasing concentrations of circulating CEA under close follow-up a linear relationship between log CEA and time could be established during disease recurrence. The individual doubling times of the serum CEA concentration in the log CEA period were calculated and found to cover distinct ranges dependent on the diagnosis of disease recurrence. The CEA doubling times concomitant with local recurrence or second primary carcinomas ranged from 142 to 868 days, visceral metastasis other than liver metastasis from 47 to 231 days and liver metastasis from 10 to 102 days. Patients with bone metastases exhibited CEA doubling times of 54-60 days and a patient with brain metastasis had a CEA doubling time of 598 days. The CEA doubling times of patients with liver metastasis and no further treatment, correlated well with the time of survival after the initial CEA increase of the log CEA phase (r = 0.870, n = 33). The mean survival expressed in multiples of the individual CEA doubling times was 7.0 +/- 1.8. Patients with liver metastasis who underwent various treatments of recurrent disease had a distinctly longer mean survival of 17.4 +/- 9.4 CEA doubling times (P less than 0.001). CEA doubling times can be used as a potential method to assess the efficacy of various treatments.

The clinical validity of circulating tumor-associated antigens CEA and CA 19-9 in primary diagnosis and follow-up of patients with gastrointestinal malignancies.

The clinical validity of monitoring the tumor markers carcinoembryonic antigen (CEA) and CA 19-9 were investigated in 602 patients with colorectal, gastric, and pancreatic carcinomas. Sensitivity and specificity of the tests were evaluated preoperatively as well as in the postoperative follow-up for early detection of disease progression and recurrence. At a 95% level of specificity as calculated from a group of 150 patients with benign diseases, the CEA test with monoclonal antibody had a preoperative sensitivity of 39% in colorectal cancer and 21% in gastric cancer. On the other hand, CA 19-9 had a sensitivity of 19% in colorectal cancer, 21% in gastric cancer, and 89% in pancreatic cancer. In the postoperative follow-up it was found that a combination of both tumor marker tests was most profitable in gastric carcinomas, yielding an increase of sensitivity from 59%-94%, showing a high degree of complementarity. The gain in sensitivity provided by the CA 19-9 test over the CEA-test in colorectal cancer was very low. The gain in sensitivity, however, provided by the CEA test over the CA 19-9 test in pancreatic carcinoma was also very low. On the basis of these results it has to be recommended that cases with pancreatic carcinoma are to be monitored most efficiently with the CA 19-9 test, whereas in cases with colorectal cancer the CEA test should be used primarily. However, in gastric cancer the combined use of CEA and CA 19-9 represents a highly valuable basis for monitoring the course of disease.

[Carcinoembryonic antigen: diagnosis and tumor progression in gastrointestinal tumors]. / Carcinoembryonales Antigen: Diagnose der Tumorprogression bei gastrointestinalen Tumoren.

Tumour progression in 340 patients with resected gastrointestinal primary tumours was monitored using the gradual increase in carcinoembryonic antigen (CEA) in serum. The commencement of the rise in CEA generally preceded clinical detection of the cancer by several months. The degree to which the rise in CEA correlated with the recurrence of cancer was investigated. There was a marked difference in the distribution of the rises in CEA between local tumour growth and distant metastases. CEA increases of more than 1 microgram CEA/l serum in 10 days occurred exclusively in patients with distant metastases. There was a further marked difference in the distribution of the CEA increase between the group with liver metastases and the groups with peritoneal carcinomatosis or other metastases. The site of the primary tumour had no influence on the CEA increase during formation of metastases.

Prognostic value of preoperative serum CEA level compared to clinical staging: III. An approach to scoring of prognostic factors in colorectal cancer.

In a clinical study of observed postoperative survival of colorectal cancer patients, we investigated the application of a risk score based on tumor-related prognostic parameters. Six hundred seventy-four patients have been registered for primary surgery of colorectal cancer since 1974 who did not receive further postoperative treatments. The prognostic parameters included operability, tumor extension, and preoperative serum carcinoembryonic antigen (CEA) level. The scoring system was based on the average death-rate ratios of subgroups of patients and their age and sex-matched reference groups derived from the general life table of the population of the Federal Republic of Germany. The individual score sums of the patients exhibited score sum ranges which characterized groups of patients with entirely different observed survival. The prediction of individual survival after primary operation was only partly possible. In the plot of individual survivals vs individual score sums, a marginal risk zone was obtained which evidently represents the zone of maximum expected survival of patients who do not receive further postoperative treatment.

[Clinical significance of the circulating tumor-associated antigen CA 19-9 in cancers of the digestive tract]. / Klinische Bedeutung des zirkulierenden tumorassoziierten Antigens CA 19-9 bei Karzinomen des Verdauungstraktes.

The relevance of the tumour associated antigen CA 19-9, defined by a monoclonal antibody, was investigated in 471 patients with carcinomas of the gastrointestinal tract and in 100 patients with benign diseases of the abdomen. In the early stages of gastric and colorectal carcinomas the sensitivity of the CA 19-9 test was between 10 and 25% and increased to about 50% in tumour stage IV. Detection rate in pancreatic carcinoma was 88% and thus markedly higher. The specificity of the test, as against the group of benign abdominal diseases, was 95%. Postoperative CA 19-9 follow-up showed unaltered individual baseline values in 192 out of 196 cases without clinical evidence of tumour progression. However, in 40 out of 61 cases (66%) with recurrencies or metastases continuous increases of CA 19-9 were observed which preceded the clinical relapse by up to 16 months (median 2 months). Concomitant determination of CEA increased sensitivity to 90% due to partial complementary information. This was particularly pronounced in gastric carcinomas in whom continuous increases of CEA involved only 58% of all patients with tumour progression. By simultaneous determination of both tumour markers this ratio rose by increases of both or one antigen to 83%.

[The doubling time of circulating CEA as an individual prognostic criterion of recurrence in patients with gastrointestinal cancers]. / Die Dopplungszeit des zirkulierenden CEA als individuelles prognostisches Kriterium bei Rezidivierung in Patienten mit gastrointestinalen Karzinomen.

In a prospective study of 928 patients with gastrointestinal cancer registered for primary resection, the postoperative carcinoembryonic antigen (CEA) time courses were analysed in connection with disease recurrence. Only patients with established diagnosis of disease recurrence and complete follow-up to death entered the evaluation of prognostic criteria of the CEA time course. In this group the CEA time courses of 103/201 patients with recurrent disease exhibited an exponential increase of the serum CEA concentration, i.e. a linear relationship of log CEA and time, which allowed the calculation of the CEA doubling time. All 103 patients developed metastatic spread and generally exhibited CEA doubling times ranging between 10 and 158 days, in patients developing peritoneal carcinosis up to 343 days. The individual CEA doubling times of patients with recurrent disease who received no treatment (n = 71) correlated well with the times of individual survival after the initial CEA increase of the log CEA phase (rs = 0.812; P less than 0.001) thus confirming the results of a previous retrospective study. When the survival time is expressed in multiples of the individual CEA doubling time (IDT), no patient survived longer than 10.8 IDT. The median value of survival was 5.4 IDT. Patients with metastatic spread who underwent various treatments of recurrent disease (n = 32) survived distinctly longer showing survival times up to 32.6 IDT. This could be confirmed by comparing the observed survival after the initial CEA increase of treated and untreated patients (life table method) exhibiting highly significant differences (P less than 0.001).

Isoflurane improves the tolerance to pacing-induced myocardial ischemia.

Fourteen patients with normal, global, left ventricular function scheduled for elective myocardial revascularization were studied at rest and during atrial pacing before and during isoflurane anesthesia (0.5% end-tidal) plus 50% nitrous oxide. Rapid atrial pacing was performed in a stepwise fashion until the onset of angina pectoris in the awake patients. The same step increase in pacing rate was applied in the anesthetized patients. Compared with prepacing baseline values, isoflurane significantly decreased systemic blood pressure, coronary perfusion pressure, the rate-pressure product, and cardiac index. No patient had ST-segment depression while awake or during isoflurane anesthesia before pacing was started. Prepacing left and right ventricular filling pressures and wave forms were normal, both while awake and during isoflurane anesthesia. The mean pacing rate at which first signs of myocardial ischemia appeared (V5 ST-segment depression greater than or equal to 0.1 mV, increase in pulmonary capillary wedge pressure (PCWP) to greater than or equal to 15 mmHg, and prominent PCWP v-waves greater than or equal to 20 mmHg) was significantly higher during isoflurane anesthesia than in the awake patients (128 +/- 4 vs. 115 +/- 5 beats/min). With the exception of one patient, the individual pacing rates inducing first signs of ischemia in the awake patients were below the anginal threshold. None of the patients had a reduced ischemic threshold during anesthesia. Eleven anesthetized patients tolerated a higher pacing rate until initial signs of ischemia appeared. In four of these patients, the pacing rate required to induce first signs of ischemia was above the heart rate at which chest pain had been induced while they were awake. At a peak atrial pacing rate of 129 +/- 5 beats/min, which had induced angina pectoris in the awake patients, the increase in PCWP was significantly smaller during pacing with isoflurane than during control pacing. Prominent PCWP v-waves (greater than or equal to 20 mmHg) appeared in 12 of the 14 patients during initial pacing to angina and in eight patients paced during isoflurane anesthesia. In six of these eight patients, the abnormal v-waves were less prominent than those observed during control pacing. Ischemic ST-segment changes developed in 13 of 14 patients during initial pacing and in nine patients during pacing with isoflurane. Mean V5 ST-segment depression during the two pacing periods was significantly different, averaging 0.19 and 0.11 mV, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Differentiation of disease recurrence in various primary malignancies using CEA slope analysis.

CEA slope analysis was performed for patients with various primary malignancies who developed recurrent disease. In 340 cases CEA slopes could be calculated, and in 289 cases correlated with distinct diagnosis of recurrent disease. Local recurrence showed a slope range of 0.02-15.2 micrograms CEA increase/l serum/10 days (median = 0.28) and metastatic spread a slope range of 0.03-456 micrograms CEA increase/l serum/10 days (median = 0.98). Subgroups of patients with metastatic spread to the liver, bone, peritoneum and other sites had distinct CEA slope distributions independent of the primary tumors. Comparable slope ranges were found with two different commercially available kits, one a radioimmunoassay (antiserum) and the other enzyme-immunoassay (monoclonal antibody).

Comparison of a CEA-EIA assay based on monoclonal antibody with a CEA-RIA assay with polyclonal antiserum.

A monoclonal CEA-EIA assay is evaluated with respect to clinically pertinent data. Comparison is done with the conventional CEA-RIA assay (Roche). Good interlaboratory reproducibility was found, and the stability was very good over the one year evaluation period. The EIA assay could be performed in samples of serum and plasma with compatible results. The correlation between the EIA and RIA values was different in different diagnostic groups, with high correlation in colo-rectal cancer, and low in non-malignant diseases, in which the EIA assay had a lower frequency of CEA positive values. In colo-rectal cancer the RIA assay shows a 20% specificity improvement compared with the EIA assay. This was also reflected in better predictability for true positive and true negative cancer diagnosis in this group of patients as well as increased ability to discriminate between malignant and non-malignant diseases. In other groups of patients, like lung cancer and uterine cervical cancer, such improvement was not seen. The discrimination between malignant and non-malignant diseases was comparable to that of the RIA assay. In follow-up series the EIA and RIA assays detected recurrences and responses to treatment in a quite similar way. In most cases of recurrences from colo-rectal cancer, however, the EIA values increased faster and were a better indicator for recurrent disease than the RIA values.

[Circulatory effects of vecuronium as well as pancuronium under different conditions of anesthesia]. / Untersuchungen der Kreislaufwirkungen von Vecuronium sowie von Pancuronium unter verschiedenen Anästhesie-Bedingungen.

The cardiovascular effects of equipotent doses (1,25 X ED95) of vecuronium (70 micrograms/kg iv) and pancuronium (80 micrograms/kg iv) were studied in 16 patients scheduled for elective coronary artery bypass surgery during steady-state conditions of isoflurane (0,4-0,5 vol% end-tidal)-nitrous oxide anaesthesia. All patients were chronically treated with oral beta receptor-blocking agents. Vecuronium did not cause any significant cardiovascular changes whereas pancuronium produced increases in heart rate (13%), cardiac index (15%) and mean arterial pressure (4%) while systemic vascular resistance decreased (8%). In a second part of this study we analysed whether the magnitude of the vagolytic effects of pancuronium is influenced by the anaesthetic procedure and/or by preoperative beta-blocker therapy. A group of 8 patients who were pretreated with beta-receptor blockers and received fentanyl (7 micrograms/kg) during the anaesthetic procedure showed low control values of heart rate (HR), cardiac index (CI), mean arterial pressure (MAP) and the rate-pressure product (RPP) which were due to both, the antisympathetic effects of beta-blocker therapy and the central vagomimetic properties of fentanyl. The administration of pancuronium (80 micrograms/kg) caused the greatest percentage increases in HR (20%), CI (22%), MAP (8%) and RPP (31%) in this group of patients. In contrast, patients (n = 8) anaesthetized with isoflurane-nitrous oxide who were not on preoperative beta-receptor blocker medication, demonstrated higher haemodynamic control values and less increases in HR (10%), CI (10%) and RPP (15%), MAP did not change. The clinical significance of these findings is discussed.

Combined effects of halothane anesthesia and verapamil on systemic hemodynamics and left ventricular myocardial contractility in patients with ischemic heart disease.

The interaction of halothane anesthesia and intravenous verapamil (0.15 mg/kg over 10 min) was investigated in eight patients scheduled for coronary artery bypass surgery. All patients had a normal left ventricular (LV) function at rest and were on chronic beta-blocker therapy. Halothane produced a marked reduction in mean arterial pressure (MAP), cardiac index, and in LV contractility as documented by a decrease in LV peak positive dP/dt. Verapamil caused an additional depression (16%) of LV peak positive dP/dt accompanied by a small increase (3 mm Hg) in LV end-diastolic pressure. The combined negative inotropic propensities of halothane and verapamil did not produce any overt untoward effects even in the presence of chronic low dose beta-blocker therapy. The predominant hemodynamic effect of verapamil was a systemic vasodilation resulting in a further reduction in MAP (12%) while heart rate remained unaffected. Despite reducing myocardial oxygen demand, caution must be exercised in dose selection in each drug to avoid regional myocardial ischemia due to the combined hypotensive effects of halothane and verapamil.