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Sepsis is a systemic inflammatory response to infection and a major cause of death worldwide. Because specific therapies to treat sepsis are limited, and underlying pathogenesis is unclear, current medical care remains purely supportive. Therefore targeted therapies to treat sepsis need to be developed. Although an important mediator of sepsis is thought to be mitochondrial dysfunction, the underlying molecular mechanism is unclear. Modulation of mitochondrial processes may be an effective therapeutic strategy in sepsis. Here, we investigated the role of the kinase MKK3 in regulation of mitochondrial function in sepsis. Using clinically relevant animal models, we examined mitochondrial function in primary mouse lung endothelial cells exposed to LPS. MKK3 deficiency reduces lethality of sepsis in mice and by lowering levels of lung and mitochondrial injury as well as reactive oxygen species. Furthermore, MKK3 deficiency appeared to simultaneously increase mitochondrial biogenesis and mitophagy through the actions of Sirt1, Pink1, and Parkin. This led to a more robust mitochondrial network, which we propose provides protection against sepsis. We also detected higher MKK3 activation in isolated peripheral blood mononuclear cells from septic patients compared with nonseptic controls. Our findings demonstrate a critical role for mitochondria in the pathogenesis of sepsis that involves a previously unrecognized function of MKK3 in mitochondrial quality control. This mitochondrial pathway may help reveal new diagnostic markers and therapeutic targets against sepsis.

In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI).Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations.Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells.In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate ( 30 %) treated significantly more patients with very low lying carcinomas ( 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.

The OCUM trial (NCT01325649) aims to clarify whether low rates of local recurrence are also achieved when the indications for neoadjuvant radiochemotherapy are not based on the clinical TNM staging but on preoperative magnetic resonance imaging with measurement of the tumor distance to the circumferential resection margin. In this interim analysis the lymph node status in OCUM patients was investigated as a surrogate parameter for quality of surgery and histopathological work-up.Until now a total of 560 patients have been included in this study. Total mesorectal excision (TME) without pretreatment was undertaken in 338 patients (60.4 %) and neoadjuvant radiochemotherapy was administered in 222 (39.6 %) patients. The histological work-up was performed according to the guidelines of the German Association of Pathologists. Data are given as median values and ranges in brackets.The lymph node yield was 24 (7-79) in 338 patients undergoing primary TME surgery without pretreatment, while 20 (3-56) lymph nodes were identified in patients after neoadjuvant radiochemotherapy (p = 0.001). A minimum of 12 lymph nodes were analyzed in 335 out of 338 patients (99.1 %) and in 209 out of 222 patients (94.1 %) following neoadjuvant radiochemotherapy (p = 0.001). Lymph node metastasis was identified (p = 0.362) in 116 out of 338 patients without pretreatment (34.3 %) and in 71 out of 222 patients after neoadjuvant radiochemotherapy (32.0 %). Patient age did not influence the number of identified lymph nodes or rate of lymph node metastasis.In this trial the number of identified lymph nodes suggests that the quality of surgery and histopathological work-up were adequate compared to the standards defined by national guidelines. Neoadjuvant radiochemotherapy led to a reduced lymph node yield compared to surgery without pretreatment; however, this did not influence the rate of lymph node metastasis.

Selective dorsal rhizotomy (SDR) is associated with moderale to severe postoperative pain. Although the efficacy of epidural analgesia in this population has been demonstrated, it has not been compared with conventional intravenous (i.v.) analgesia. This prospective study compared the effects of epidural and i.v. morphine regarding postoperative analgesia, side effects, and outcomes in children following SDR.Twenty-seven children were randomized to receive either epidural or i.v. analgesia. Children in the epidural group had a catheter placed by the neurosurgeon and received preservative-free morphine (Duramorph) 30 microg/kg, followed by an infusion of 3 microg/kg/h for 3 days. Children in the i.v. group received morphine 0.05-0.1 mg/kg intraoperatively, followed by 0.02 mg/kg doses postoperatively administered by nurses via a patient-controlled analgesia device.The epidural group experienced lower pain scores (P = .04) and fewer muscle spasms (Por = .04), and tolerated activity better (Por = .02) during the early postoperative period than the i.v. group. Side effects were similar between groups, with no respiratory depression in either group. Parents of children in both groups perceived an adequate level of comfort and were very satisfied with the analgesic technique. Additionally, parents believed that their child's postoperative pain was less than anticipated (Por = .01).Both techniques provided effective postoperative analgesia with a similar incidence of side effects; however, our findings suggest that continuous infusions of epidural morphine improved overall comfort with lower pain scores, fewer muscle spasms, and improved tolerance of activity during the initial postoperative period.

Concerning younger patients with colorectal carcinoma (CRC) controversies still exist regarding outcome. The aim of this study was to evaluate possible differences between patients suffering from CRC at a younger age ( 40 years) and at an age over 40 years.Data of 51 younger patients ( 40 years) and 2122 older patients (≥ 40 years) were prospectively collected and retrospectively evaluated according to clinical parameters, treatment and prognosis. Patients with a CRC arising from familial adenomatous polyposis, ulcerative colitis or Crohn's disease have been excluded.The younger patients presented significantly more often with mucinous adenocarcinomas (p = 0.033). There were no differences between the groups concerning gender, localisation, elective and emergency surgery, UICC (Union internationale contre le cancer) stages and residual tumour classification. Postoperative therapy - in adjuvant, therapeutic or palliative intent - was applied significantly more often in younger patients, especially in those with colon carcinoma (p = 0.001). After curative resection of colon carcinoma a significantly better observed (5 year rate 94 vs. 76 %; p = 0.024) and disease-free (88 vs. 69 %; p = 0.013) survival were found. This trend was similar in patients with rectal carcinoma (84 vs. 75 % and 72 vs. 65 %) without reaching the level of significance (p = 0.155 and 0.269). Taking into account differences in life expectancy, just minor differences were detected in relative survival (colon carcinoma, 5 year rate 94 vs. 89 %; rectal carcinoma, 84 % both).The general assumption of a poorer prognosis in younger patients with CRC could not be confirmed. Younger patients have a poorer histological subtype of carcinoma. But this is compensated by the better overall condition, less comorbidities, faster postoperative recovery and an optimally organised post-operative (adjuvant, therapeutic or palliative) therapy. In summary, younger patients have a better observed survival but - considering differences in life expectancy - a similar relative survival.

Despite its dwindling occurrence, gastric cancer remains a leading cause of cancer related mortality worldwide. Molecular determinants of prognosis that impact survival are being sought out as a means to facilitate rational clinical decision-making and enhance patient management. In this study, we evaluated three molecules implicated in gastric carcinogenesis and demonstrated that the differential expression of cyclooxygenase-2 (COX-2) and the viral oncogene homolog Src proteins could explain the differences in survival observed in patients older and younger than 50 years of age.We evaluated 5-year survival in a cohort of 423 gastric cancer patients using chronological age as a variable. Additionally, we assessed the protein expression of three molecules (COX-2, TFF1, Src) implicated in the pathogenesis of gastric cancer using immunohistochemistry.We found that patients younger than 50 years of age had a better 5-year survival rate in all tumor stages. We found that the expression of COX-2 and Src correlated significantly with survival in this group without any significant impact attributable to TFF1.Our study demonstrates that young gastric cancer patients have a better prognostic outlook that could in part be explained by the differential expression of COX-2 and Src.

OBJECTIVE: To identify dietary, psychological, and physiological characteristics of older individuals with chronic constipation, compared with a control group of individuals without constipation, and identify correlates of colonic transit time. DESIGN: Cohort study. SETTING: University hospital and affiliated clinics. PARTICIPANTS: Eighteen constipated and 18 control subjects who were nondemented, ambulatory, community-dwelling outpatients over the age of 60 years. MEASURES: Measures included a 1-week food diary, diet questionnaire, bowel diary, the Hopkins Symptom Checklist (SCL-90R), colonic transit study, and medical history, including queries about activity, medications, medical illnesses, and bowel symptoms. MAIN RESULTS: Constipated subjects reported consuming fewer meals per day compared with control subjects (P < 0.01) and a tendency to consume fewer calories (P = 0.07). There were no differences between groups on fiber or fluid intake or any of the other dietary parameters. However, slow colonic transit was significantly related to low caloric intake (P < 0.0001), higher percent of protein in the diet (P < 0.05), low fluid intake (P < 0.05), and to psychological symptoms of somatization, obsessive-compulsiveness, depression, anxiety, and the global severity index (P < 0.05). Transit times were unrelated to crude or dietary fiber intake, activity level, or age. CONCLUSIONS: The data suggest that constipation in this older population is related to caloric intake rather than fiber consumption or other dietary qualities. Psychological distress is associated with slowed colonic transit and should be investigated further as a possible etiologic factor in constipation.

About 10% of all operations in colon carcinoma are performed in emergency situations because of severe preoperative complications.The prospectively collected data of 1496 patients with colon carcinoma treated from 1987 to 2002 at the Department of Surgery of the University of Erlangen were analysed with special interest on postoperative morbidity and long-term prognosis after elective and urgent surgery.The rate of urgent surgery was 11%. The most frequent complication was bowel obstruction (73%) followed by perforation (20%). Emergency patients were significantly older (p0.001) and in worse general condition (p0.001). The rates of surgical and nonsurgical postoperative complications were higher in urgent surgery than in elective surgery (28.8% vs. 19.8%, p=0.015) and also postoperative mortality was significantly higher (10.1% vs. 4.0%, p0.001). The rates of locoregioanal recurrences and distant metastases were significantly higher. Urgent surgery was found to be an independent prognostic factor for distant metastasis (relative risk 1.8) and cancer-related survival (relative risk 1.6).Urgent surgery in colon carcinoma is usually performed in advanced tumours of elderly patients. This operation can be a challenge for the treating surgeon. Adequate medical emergency supply needs to provide an experienced surgeon for those interventions.

Surgery of diseases of the pelvis minor and retroperitoneum such as inflammatory disease, malignant tumours, or trauma of pelvic organs need the close interdisciplinary collaboration of visceral surgeons, gynaecologists, and urologists. This collaboration begins in planning diagnostic and therapeutic procedures. It has to be clear who performs which operative step and when. Excellent long-term results in malignant disease show that the greater effort is worthwhile. The rate of postoperative morbidity after these multivisceral resections is high also in specialised centers, but mortality is below 5%. Because of the growing number of long-term survivors, preservation of quality of life becomes more and more important.

In the therapeutic algorithm for treatment of rectal cancer, primarily in the lower two-thirds of the rectum, local excision currently plays a limited role, but clearly adheres to diagnostic, oncologic, and technical principles. This should be considered particularly against the background that aspects of maintaining function and the associated positive effects on quality of life, based on expanding knowledge of the complications of radical interventions and their ramifications, have gained in importance. The following addresses the oncologic-histologic, clinical-diagnostic, and technical principles of local excision as well as the results for patients treated according to the devised diagnostic/therapeutic algorithm and included in the Erlanger Register of Colorectal Cancer (ERCRC).

In an analysis over 22 years it was investigated which parameters have changed in the operative treatment of thoracic esophageal carcinoma over time and in how far they have influenced complication rate.Between 1978 and 1999 386 patients (350 men, 36 women) underwent resection for thoracic esophageal carcinoma (squamous cell carcinoma n=300, adenocarcinoma n=86). Cervical tumors were excluded from analysis. The time periods from 1978 to 1988 (n=242) and from 1989 to 1999 (n=144) were separately analyzed and compared with respect to age, sex, histological type, main tumor location, neoadjuvant therapy, method of operation, esophageal substitute and positioning of the substitute, R-status, pT/pN classification, UICC stage, number of dissected lymph nodes, complication rate, postoperative mortality and survival.Comparison of the two time periods showed a significant increase in adenocarcinomas and main tumor location in the lower thoracic third of the esophagus. Furthermore, significant changes concerning the indication of neoadjuvant chemoradiation, operative approach, esophageal substitute, R-status and number of dissected lymph nodes were observed. Tumor stage (pT/pN classification and UICC stage) significantly shifted towards earlier stages. Total complication rate dropped tendentially form 68.5 % to 59.0 % (p=0.061). Hospital mortality was significantly reduced from 24 % to 12.5 %, whereas anastomotic leakages and multiorgan failure remained on a constant level. Median survival of R0 resected patients was significantly prolonged from 19 months to 34 months.The increase of esophageal adenocarcinoma, a more strict patient selection (staging, functional status), standardization of operative technique as well as an optimized intensive care management are among the important changes in the operative management of thoracic esophageal carcinoma that have resulted in an improvement of prognosis of curatively resected patients. In spite of a more aggressive operative approach, i. e. lymph node dissection, operative mortality could be reduced by nearly 50 % in the face of a tendentially declining total complication rate.

In western countries, the benefit of the Japanese extended D3 lymph node dissection in gastric cancer patients who have been operated on in curative intent has not been proven and higher rates of side effects are expected. The present matched-pair study retrospectively compared the new D3 method (1995-1999) with the historic D2 dissection (1982-1995).Two 1:1 matched-pair populations were created: (1) regarding intra- and postoperative course, morbidity and mortality, 2 x 67 patients stratified to "age", "gender", "surgical procedure", "splenectomy" and "extended resections"; and (2) regarding early oncologic outcome, 2 x 32 patients additionally stratified to "UICC-stage" and "Laurén-classification". The D3 dissection was performed according to the Japanese method without routine pancreaticosplenectomy.D3 dissection harvested significantly (P = 0.004) more lymph nodes per patient: 56.4 vs. 46.8. Postoperative mortality was 3% (n = 2) in both groups, the overall complication rate of 30% (D3) vs. 25% (D2) was equivalent (P = 0.678) and the rate of surgical complications was identical (21%). Non-surgical complications of 21% after D3 dissection were not significantly elevated (vs. 10%; P = 0.143). Operative time [289 min (D3) vs. 218 min (D2); P = 0.0001] and postoperative stay [17.4 days (D3) vs. 14.5 days (D2); P = 0.003] were significantly longer after the extended procedure. The were no statistically significant differences between 2-year overall survival, locoregional-, distant- and overall recurrence-free survival.Compared to the D2 method, D3 dissection is feasible without disadvantages in the patients. However, D3 dissection cannot routinely be recommended because--possibly due to the short follow-up period and the small number of patients so far observed--an oncologic benefit could not be shown.

Dysfunction of the parathyroid glands is a typical complication following thyroid surgery. Risk factors for the development of postoperative symptomatic hypocalcemia were retrospectively analyzed.308 consecutive thyroid resections (women n = 236, men n = 72, mean age 53 years) performed in 1996 and 1997 were evaluated. Main diagnosis was non-toxic nodular goiter (n = 234, 76 %), 28 patients (9 %) had thyroid carcinoma. The most common operation performed was bilateral functional thyroid resection (n = 116, 38 %), the proportion of thyroidectomies was 14 % (n = 44). The patients with postoperative symptomatic hypocalcemia were followed for a median of 32 months.Clinical symptoms of hypocalcemia were observed in 18 patients (6 %) postoperatively. Three patients developed transient (n = 1) or permanent hypothyroidism (n = 2). In univariate analysis, the underlying thyroid disease, the method of operative therapy, removal, identification and autotransplantation of parathyroid glands, in multivariate analysis, thyroidectomy (relative risk 6.9) and removal of parathyroid glands (relative risk 23.9) were proved to be significant risk factors for the development of postoperative symptomatic hypocalcemia (p0.05).Patients with thyroidectomy, operation for thyroid carcinoma and intraoperative removal of parathyroid glands should be closely followed for postoperative hypocalcemia. Exact surgical technique provided, permanent hypoparathyroidism is rare, particularly if several parathyroid glands were identified intraoperatively and autotransplanted, if necessary.

Besides quality, costs play an increasingly important role. For rectal carcinoma, the cost of the surgical treatment of the disease (including after-care) was analysed under variable clinical conditions.Eleven patients (eight men, three women, median age 57 years) with curative resection of rectal carcinoma between 1991 and 1995 were selected: Five patients with an uneventful course remaining recurrence-free, three patients who developed an anastomotic leakage and three patients with locoregional recurrence during their further course. In three patients, adjuvant radiochemotherapy was performed after resection of the primary tumor. For each patient, costs from the first postoperative day until the end of an assumed after-care of 5 years' duration were analysed.Costs for the postoperative period of the primary treatment ranged between 3.162 DM and 149.988 DM, in case of development of an anastomotic leakage between 14.699 DM and 149.988 DM. Adjuvant radiochemotherapy increased costs by 12.265 DM up to 23.259 DM, locoregional recurrence caused additional costs between 9.461 DM and 27.301 DM. Cost group analysis showed the costs for nursing care to be the highest (30% of total costs), followed by the expense for drugs and medication. Total costs of treatment ranged from 7.361 DM to 160.833 DM.Costs as well as the patient's prognosis depend to a great extent on the quality of the procedure and consequently on the individual operating surgeon. A complicated course is associated with a considerable increase in costs. A complete cost analysis of rectal carcinoma has to include the cost of a potential locoregional recurrence which would lead to the additional prolonged after-care for these patients.

The prognosis of patients with Stage III colorectal carcinoma seems to be inhomogeneous. Therefore a subdivision of Stage III was performed.Data from 850 patients of the Erlangen Registry of Colo-Rectal Carcinomas and 603 patients of the Study Group Colo-Rectal Carcinoma (SGCRC) with Stage III colorectal carcinoma were analyzed. Three different subdivisions of Stage III were performed according to pT, pN, and pTpN. Observed 5-year survival rates for all possible substages were calculated according to Kaplan-Meier. To compare the predictive value of several possible substages, Brier-Score and receiver operator charcteristics (ROC) analysis were applied.The subdivision according to pT (pT1,2pN1,2 versus pT3 pN1,2 versus pT4 pN1,2) as well as the subdivision according to pN (any pT pN1 vs. any pT pN2) resulted in significant differences of observed 5-year survival rates. However, subdivision according to pT and pN (pT1,2 pN1 vs. pT3,4pN1 and pT1,2pN2 vs. pT3,4 pN2) was found to be superior. The three substages, IIIA, IIIB, and IIIC, identified 10%, 50%, and 40% of the patients with observed 5-year survival rates of 80%, 60%, and 30%, respectively. Using Brier-Score and ROC analysis an increase in predictive power was found, especially for the patients of the Erlangen Registry, but less clearly for SGCRC patients.Subdivision of Stage III colorectal carcinoma into three substages according to the pT and pN categories resulted in subgroups which differed significantly in prognosis. This may be important for comparing treatment results, especially in adjuvant treatment and patient care evaluation studies.

Epidemiologic data suggest that an underlying genetic disposition can be detected in up to 10% of all colorectal cancer patients and autosomal dominantly inherited hereditary non-polyposis colorectal cancer (HNPCC) is the entity most frequently identified. It was described first by A. Warthin in 1895 in "Family G" and is characterized by a predisposition to an early onset of colorectal cancer and other intestinal or genitourinary tumors. We report the case of a 61-year-old woman with five different cancers. Although the strict Amsterdam Criteria were not fulfilled, molecular analysis revealed HNPCC; further genetic testing in the family confirmed that the 36-year-old and so far healthy son had inherited the germline mutation of his affected mother. Genetic testing in clinically suspected HNPCC cases is recommended for patients with colorectal cancer meeting the Amsterdam Criteria. In patients meeting one of Bethesda Criteria 2-7 without meeting the Amsterdam Criteria, germline mutation analysis is recommended only in MSI-positive tumors.

To characterize colorectal physiologic parameters and psychological profiles in subjectsor = 60 yr with chronic constipation who have not sought medical advice.Colorectal physiologic studies and psychologic profiles were obtained in 18 self-identified constipated subjects and 17 nonconstipated control subjects. Constipation was defined as two or fewer bowel movements/week and/or defecatory difficulty for at least 6 months. All subjects underwent colonic transit with radiopaque markers, anorectal manometry and completed a self rated inventory assessing psychological distress (SCL-90-R).Slow colonic transit occurred in five constipated subjects. Pelvic floor dyssynergia and/or increased rectal compliance were found in nine subjects versus only two controls. One-third of constipated subjects scored in the top 10th percentile for global psychologic distress with higher scores for somatization, depression, and anxiety than control subjects. Neither physiologic nor psychologic abnormalities were predictable on the basis of patterns of bowel complaints.Colorectal physiologic and psychologic dysfunctions are common in elderly constipated subjects who do not seek medical attention for bowel dysfunction.

Patients with advanced liver disease are at increased risk for the development of hepatic osteodystrophy in the form of either osteomalacia or osteoporosis. The pathogenesis of these two bone diseases is multifactorial and includes, among other factors, alterations in vitamin D metabolism, malnutrition and hypogonadism. Little is known regarding vitamin D metabolism and the osteoblastic activity in liver transplant recipients. In order to clarify these issues, vitamin D metabolites and osteocalcin levels were measured prior to and 30 days following liver transplantation in 30 cirrhotic patients of various etiologies. While the mean plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D of the entire group of 30 patients were significantly greater prior to orthotopic liver transplantation (OLTx) as compared to those after OLTx (11.5 +/- 8.6 vs. 7.4 +/- 5.8 ng/ml, p = 0.0066 and 41.0 +/- 34.6 vs. 20.4 +/- 11.0 pg/ml, p = 0.0003, respectively), no significant changes in osteocalcin concentrations pre- or post-transplantation could be demonstrated (5.2 +/- 3.0 vs. 6.4 +/- 4.1 ng/ml, p = 0.51). Furthermore, no correlation between the plasma concentration of osteocalcin and either vitamin D metabolite, the prothrombin time or cyclosporine levels was found. The reasons for the normal levels of osteocalcin prior to OLTx can be explained by the fact that in vitamin-K-deficient states osteocalcin is predominantly decarboxylated and, therefore, a smaller proportion is bound to bone and/or the synthesis of osteocalcin is partially modulated by 1,25-dihydroxyvitamin D, the level of which has been found to be normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumocystis carinii infection of the liver is being reported with increasing frequency in patients with acquired immune deficiency syndrome (AIDS). The clinical picture typically resembles hepatitis. We report such an occurrence in a patient with persistent elevation of alkaline phosphatase and gamma-glutamyl transpeptidase with relatively normal transaminases who was found to have P. carinii on antemortem liver biopsy. The differential diagnosis of abnormal alkaline phosphatase and gamma-glutamyl transpeptidase in patients with AIDS should include P. carinii.

Since 1980 an increase of the frequency of osteomyelitis after BCG vaccination has been described by some european countries. In the GDR osseous impairments as BCG complication are rarely. The authors report on an 18 months old boy with lesions of the distal tibia and the ankle-joint. He was vaccinated with BCG in the neonatal period. In contrast to the local findings general symptoms were unimportant. The surgical treatment was completed by antituberculotic chemotherapy. This treatment was successful.

In 3,296 school-leavers (girls and boys aged 16 years with preceding BCG-vaccination as newborns and without boosting by tuberculin-testing or revaccination during the meantime) simultaneously with compulsory BCG-revaccination tuberculin testing with 2 TU PPD Dessau + Tween 80 was performed in 3 regions of the GDR (Cottbus, Erfurt, Neubrandenburg) in the 2nd half of 1985 and in the 1st quarter of 1986. Sensitivity to tuberculin was found in 7.3% considering reactions with greater than or equal to 6 mm induration as positive, and in 2.9% considering reactions with greater than or equal to 10 mm only. Positive reactions greater than or equal to 6 mm include remaining allergy caused by BCG and non-specific tuberculin sensitivity while a reaction limit greater than or equal to 10 mm is suitable to define tuberculosis infection prevalence. In contrast to studies performed 1973 and 1979 in the same territories a significant decrease in tuberculin sensitivity was evident (43.8% positive reactions (greater than or equal to 6 mm) in 1973 and 11.7% in 1979). The acceptability of "direct" BCG-revaccination has been estimated by evaluation of local reactions 4 weeks after vaccination in 2,123 school-leavers. The ulceration rate in tuberculin positive adolescents was significantly higher than in tuberculin negative. It showed highly significant decrease in comparison with 1979.

144 patients with bacteriologically positive results were analysed out of 258 relapses of pulmonary tuberculosis within one year (1979/80) to find the causes which are favouring relapses. It has been found that in 28% an inadequate chemotherapy, in 16% uncontrolled use of drugs, and in 13% of cases uncooperative attitude of patients were supposed causes of relapse. Causes of relapse could not be established in 23% of patients. Silicosis and chronic alcoholism were observed in 22% of patients with relapse.