[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome]. / Eine deutsche Fassung der Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities : Ein Diagnoseverfahren zur Erfassung von Demenz bei Menschen mit einem Down-Syndrom.

BACKGROUND: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language. OBJECTIVE: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview. METHODS: The translation and adaptation of the CAMDEX-DS were achieved through a multistep translation process, whereby two independent forward and back translations were provided by professional translators and a consensus version was finalized and tested. The final version of the caregiver interview was applied to 11 subjects and the CAMCOG-DS was conducted with 28 patients. RESULTS: The German version of the CAMDEX-DS proved to be easily administered. The CAMCOG-DS could be fully administered to 21 out of 28 patients (75%). The CAMCOG-DS values were much lower for older patients aged ≥45 years than for younger patients (46/109 vs. 73.5/109; p = 0.033). DISCUSSION: The German version of the CAMDEX-DS provides an internationally recognized tool for the diagnostics and monitoring of cognitive decline in Down's syndrome. Furthermore, the German version can standardize medical care of these patients. In particular it provides a means of participation in international research trials for this at risk population.

Negligible risk of prenatal ductus arteriosus closure or fetal renal impairment after third-trimester paracetamol use: evaluation of the German Embryotox cohort.

OBJECTIVE: Risk of fetotoxicity after paracetamol exposure in the third trimester. DESIGN: Observational cohort study and retrospective case assessment. SETTING: Germany, 2008-2017. POPULATION: Pregnant women exposed to paracetamol. METHODS: Prospectively enrolled third-trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox 'adverse drug reaction in pregnancy' database was screened for cases of fetotoxicity. MAIN OUTCOME MEASURES: The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function. RESULTS: In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co-exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity. CONCLUSIONS: Fetal cardiovascular or renal toxicity of maternal third-trimester paracetamol use appears to be negligible. TWEETABLE ABSTRACT: Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.

[Psychotherapy of depressive disorders: Evidence in chronic depression and comorbidities]. / Psychotherapie depressiver Störungen: Evidenz bei chronischer Depression und bei Komorbidität.

BACKGROUND: Psychotherapy has been shown to be an effective treatment option for depressive disorders; however, its effectiveness varies depending on patient and therapist characteristics and the individual form of the depressive disorder. OBJECTIVES: The aim of this article is to present the current evidence for psychotherapeutic antidepressive treatments for patients with chronic and treatment-resistant depression as well as for patients with mental and somatic comorbidities. MATERIAL AND METHODS: During the revision of the currently valid German S3- and National Disease Management Guideline (NDMG) on unipolar depression published in 2015, a comprehensive and systematic evidence search including psychotherapy for specific patient groups was conducted. The results of this search along with a systematic update are summarized. RESULTS: Psychotherapy has been shown to be effective in reducing depressive symptoms in patients suffering from chronic and treatment-resistant depression and in patients with mental and somatic comorbidities. The evidence is insufficient particularly for patients with mental comorbidities. CONCLUSION: Based on the current evidence and clinical expertise the NDMG recommends psychotherapy alone or in combination with pharmacotherapy to treat most of these depressive patient groups. Evidence gaps were identified, which highlight the need for further research.

[Psychotherapy of depressive disorders : Procedures, evidence and perspectives]. / Psychotherapie depressiver Störungen : Verfahren, Evidenz und Perspektiven.

BACKGROUND: Depressive disorders are associated with a high burden of suffering and significantly reduce the well-being and the self-esteem of affected patients. Psychotherapy is one of the main treatment options for depressive disorders. OBJECTIVE: The aim of this article is to present the current evidence for antidepressive psychotherapeutic treatments. MATERIAL AND METHODS: During the revision of the German S3- and National Disease Management Guideline (NDMG) on unipolar depression in 2015, a comprehensive and systematic evidence search was conducted. The results of this search along with a systematic update are summarized. RESULTS: The most intensively investigated psychotherapeutic method is cognitive behavioral therapy (CBT), which proved to be effective in many trials. Evidence also exists for psychodynamic psychotherapy and interpersonal therapy (IPT), followed by systemic therapy and client-centered psychotherapy; however, the evidence is less robust. CONCLUSION: Psychotherapy alone or in combination with pharmacotherapy was shown to be an effective treatment option. Psychotherapy represents a key element in the treatment of depressive disorders.

Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions.

Oral compared to parenteral estrogen administration is characterized by reduced systemic but prominent hepatic estrogenic effects on lipids, hemostatic factors, GH-/IGF I axis, angiotensinogen. In order to avoid such adverse metabolic effects of oral treatment, estradiol (E2) prodrugs (EP) were designed which bypass the liver tissue as inactive molecules. Carbone17-OH sulfonamide [-O2-NH2] substituted esters of E2 (EC508, others) were synthesized and tested for carbonic anhydrase II (CA-II) binding. CA II in erythrocytes is thought to oppose extraction of EP from portal vein blood during liver passage. Ovariectomized (OVX, day minus 14) rats were orally treated once daily from day 1-3. Sacrifice day 4. Uteri were dissected and weighed. Cholesterol fractions and angiotensinogen were determined in plasma. Oral E2 and ethinyl estradiol (EE) generated dose related uterine growth and important hepatic estrogenic effects. EP induced uterine growth at about hundred-fold lower doses. This was possible with almost absent effects on plasma cholesterol or angiotensinogen. Preliminary pharmacokinetic studies with EC508 used intravenous and oral administration in male rats. Resulting blood levels revealed complete oral bioavailability. Further high blood- but low plasma concentrations indicated erythrocyte binding of EC508 in vivo as potential mechanism of low extraction at liver passage. Very high systemic estrogenicity combined with markedly lower or absent adverse hepatic estrogenic effects is evidence for a systemic release of E2 from sulfonamide EP. In conclusion, tested oral EP bypass the liver in erythrocytes furnishing systemic estradiol at hydrolysis. This mechanism avoids the hepatic estrogenic impact of conventional oral estrogen therapy.

Follow-up Reality for Breast Cancer Patients - Standardised Survey of Patients and Physicians and Analysis of Treatment Data.

Introduction: Currently, about 360 000 breast cancer patients who could, after completion of their primary therapy, take advantage of follow-up options are living in Germany. Up to now very little is known about the extent to which the available options are used and as to how the follow-up reality is experienced and evaluated. Thus, an explorative examination among the patients and their physicians was undertaken. Patients and Methods: All patients who underwent surgery in a certified breast centre between 2007 and 2013 received a standardised questionnaire; at the same time the physicians responsible for the follow-up were invited to answer a standardised questionnaire. Results: 920 patients (response rate: 61 %) with a median age of 65 years (32-95) could be analysed. 99 % of the participants stated that they regularly attended follow-ups. The personal contact with the physician (mean value: 4.4) and the reassurance that the cancer disease had not recurred (mean value: 4.5) were described on a scale of 0 to 5 to be two of the most important factors of the follow-up. Deficits were expressed with regard to psychosocial care (70 %) and the perception and treatment of physical complaints (55 %). In addition, 105 physicians returned completed questionnaires (response rate: 12 %). For asymptomatic patients the physicians performed the following examinations most frequently: anamnesis (92 %), physical examination (87 %) as well as laboratory tests (63 %) and tumour marker determinations (40 %). Conclusion: On the whole it became clear that the vast majority of the patients took advantage of the follow-up options. From the patient's perspective the importance of the follow-up lies in contact to the physician and the comforting assurance that the breast cancer has not relapsed. Deficits are seen in the psychosocial care and the perception and treatment of physical impairments. Not recommended examinations were employed by a significant proportion of the surveyed physicians.

Inhibitory effect of glucose on the maturation of rat liver mitochondria at birth. Phospholipid and oxidative metabolism.

(1) The rate of ATP synthesis coupled with succinate oxidation in rat liver mitochondria is low at birth and increases rapidly during the first postnatal hours (Nakazawa, T., Asami, K., Suzuki, H. and Yakawa, O. (1973) J. Biochem. 73, 397-406). A glucose injection given to newborn rats immediately after birth seemed to delay this maturation process. (2) Glucose administration specifically diminished the rate of 32Pi incorporation into phosphatidylcholine both in microsomes and in mitochondria while other phospholipids remained unaffected. (3) In newborn rat liver, 32Pi incorporation into phospholipids can be explained by de novo synthesis of phospholipids in microsomes followed by transfer to mitochondria with two exceptions phosphatidylserine and sphingomyelin. Indeed, after a 20-min incorporation of 32Pi into phospholipids, the specific radioactivity of phosphatidylserine and sphingomyelin was higher in mitochondria than in microsomes. (4) As far as phospholipid synthesis is concerned, no precursor-product relationship could be observed between light and heavy mitochondria.

Cyclic GMP, cyclic AMP, glucose at birth, and maturation of rat liver mitochondria.

The improvement in mitochondrial functions which normally occurs in newborn rat liver in vivo during the few hours following delivery is inhibited by a glucose injection at birth (Meister, R., Comte, J., Baggetto, L., G., Godinot, C. and Gautheron, D.C. (1983) Biochim. Biophys. Acta 722, 36-42). To test whether this improvement could be correlated to changes in cyclic nucleotides, the levels of cAMP and cGMP have been measured during the 2 h following birth. At birth, a short rise followed by a decrease of cAMP occurs, then a significant increase of cAMP level is observed between 45 min and 2 h. The cAMP level for animals injected at birth with glucose is lower than for control animals at each time studied. The cGMP level is not significantly affected in control animals, while in glucose-treated animals a significant decrease of cGMP is observed in the postnatal 2 h. The present work shows also that the glucose-induced inhibition of mitochondrial maturation is mimicked by injection at birth of either 8-Br-cGMP or nitroprusside. The latter transiently increases intracellular cGMP. In contrast, the glucose-induced inhibition is prevented by the injection at birth of either dbcAMP or alkylxanthines together with glucose (Comte, J., Meister, R., Baggetto, L.G., Godinot, C. and Gautheron, D.C. (1986) Biochem. Pharmacol. 35, 2411-2416). It is concluded that the postnatal improvement of mitochondrial functions is stimulated by cAMP and inhibited by cGMP, and that glucose-induced inhibition of the maturation is at least partly supported by a decrease in cAMP but not correlated to an increase in cGMP.

Testing differential gene expression in functional groups. Goeman's global test versus an ANCOVA approach.

OBJECTIVES: Single genes are not, in general, the primary focus of gene expression experiments. The researcher might be more interested in relevant pathways, functional sets, or genomic regions consisting of several genes. Efficient statistical tools to handle this task are of interest to research of biology and medicine. METHODS: A simultaneous test on phenotype main effect and gene-phenotype interaction in a two-way layout linear model is introduced as a global test on differential expression for gene groups. Its statistical properties are compared with those of the global test for groups of genes by Goeman et al. in a preliminary simulation study. The procedure presented also allows adjusting for covariates. RESULTS: The proposed ANCOVA global test is equivalent to Goeman's global test in a setting of independent genes. In our simulation setting for correlated genes, both tests lose power, however with a stronger loss for Goeman's test. Especially in cases where the asymptotic distribution cannot be used, the stratified use of the ANCOVA global test shows a better performance than Goeman's test. CONCLUSIONS: Our ANCOVA-based approach is a competitive alternative to Goeman's global test in assessing differential gene expression between groups. It can be extended and generalized in several ways by a modification of the projection matrix.

[Comparative metabolism of phospholipids of osmoregulation effector organs in European eel (Anguilla anguilla)]. / Métabolisme comparé des phospholipides des organes effecteurs DE L'osmorégulation chez l'anguille européenne (Anguilla anguilla)

The phospholipid composition from various organs of the fresh water eel, such as gill, kidney, gut, liver and muscle, were determined by thin-layer chromatography. The major phosphatides found in these tissues were PC, PE and SPH and minor constituents PS, PI, DPG, AP and also LPC in the gut. A greater percentage of PS and SPH occurs in the osmoregulatory effector organs such as gill, kidney, and gut. From in vivo comparative kinetic studies of the 32P incorporation into the phospholipids, between 6 and 48 hours, certain remarkable features of phospholipid metabolism have been found in these tissues. A low uptake of inorganic 32P into the tissue lipid phosphorus was observed in the eel at 15 degrees C. The specific activity of the lipid phosphorus increased continuously in all tissues during 48 hours after 32P injection. During this experimental period, phosphatidic acid and phosphatidyl inositol fractions were labelled most rapidly in gill, kidney and gut, while the specific activity of the phosphatidyl choline fraction remained low in these organs. In liver, the rate of PC formation appears to be faster than the PI and PE biosynthesis. In gill and gut, the PE showed greater turnover than the PC as measured by 32P incorporation. In the eel, an euryhalin fish, the DPG of osmoregulatory effector organs has a high specific activity at all times. PS showed only a high specific activity in the gill. Labelling of SPH occured slowly in the various tissues only becoming evident after 24 hours. The results are compared with those published for other poikilotherm and homeotherm vertebrates. Relative differences between the turnover of various tissue phosphatides are discussed with of reference to the general scheme on phospholipid biosynthesis and to the physiological functions of the various organs.

High phosphate requirement for oxidative phosphorylation and low affinity for phosphate transport in newborn rat liver mitochondria.

Rat liver mitochondria are not fully functional at birth. The relationship between this deficiency and the affinity for phosphate, in oxidative phosphorylation or in phosphate transport, have been studied. The phosphate concentration necessary to observe maximal rate of succinate oxidation in the presence of ADP was higher for newborn than for adult rat liver mitochondria. After preincubation of newborn rat liver mitochondria with ATP, the rate of succinate oxidation in the presence of ADP increased with phosphate concentration similarly for newborn and adult rat liver mitochondria. The maximal rate of phosphate-acetate exchange, which is an indirect measure of the rate of phosphate transport across the mitochondrial membrane, was not significantly different for adult and newborn rat liver mitochondria. On the contrary the apparent affinity for phosphate was about ten-fold lower for newborn than for adult mitochondria.

Cannabinoids. 1. 1-Amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo [b,d]pyrans.

A series of 1-amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans was synthesized and subsequently evaluated in three rodent test systems for CNS activity. The structure-activity data generated indicate that, in general, a change of the 1-hydroxy group to an amine results in a retention of pharmacological activity but that a change to sulfur results in loss of pharmacological activity. Derivatization of the 1-amino group with various functions decreased the activity of the parent compound. For optimum potency, in all series, the 3-position alkyl side chain should be either 1,1- or 1,2-dimethylheptyl. With either the 1-hydroxy- or 1-amino-7,8,9,10-tetrahydro-3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (4c or 10c), preparation of the optically active antipodes did not lead to any great degree of spearation of activity. Both of the antipodes possess pharmacological activity as measured in these rodent test systems.

Cannabinoids. 2. Synthesis and central nervous system activities of some B-ring homocannabinoid derivatives and related lactones.

The syntheses of some novel B-ring homocannabinoid derivatives 1,2, and 4 and related lactones 3 and 5 are described. Compounds 1-5 are 6,7,8,9,10,11-hexahydrodibenz[b,d]oxepins. CNS structure-activity correlations were determined using three rodent models. The potency and activity profile of these seven-membered ring compounds were compared with the corresponding six-membered ring homologues 6 and 7. A possible seperation of CNS activities was noted with compound 1. Unexpected pharmacological activity was discovered with lactone 3, which was about equipotent to 1-delta9-tetrahydrocannabinol. It was found that dimethylation at the 7 postition decreased CNS activity when the 6 position was either a carbonyl or methylene group.

Reversal of glucose-induced inhibition of newborn rat liver mitochondrial maturation by administration of alkylxanthines at birth.

A glucose injection given immediately after birth delays the maturation which normally occurs in rat liver mitochondria and which increases the rate of ATP synthesis coupled to succinate oxidation from a low value at birth to the adult value a few hours after birth [R. Meister, J. Comte, L. Baggetto, C. Godinot and D. C. Gautheron, Biochim. biophys. Acta 722, 36 (1983)]. Alkylxanthine (pentoxifylline, HWA 285) administration at birth has no effect on the maturation of mitochondria prepared from 2-hr-old rat livers while DBcAMP administration increases their RCR and their rate of ATP synthesis. On the contrary, both alkylxanthines and DBcAMP reverse the glucose-induced inhibition of mitochondrial maturation. This DBcAMP effect cannot be mimicked by butyrate and is therefore related to cAMP. The cAMP content of rat liver increases during this postnatal period in both control and glucose-treated rats, although glucose administration tends to decrease the level of cAMP. Alkylxanthine administration restores after 2 hr the cAMP level in glucose-treated animals. The variations of RCR could not be completely correlated with the level of cAMP. The possible involvement of other factors in the mitochondrial maturation and the glucose effect is discussed.

Differentiation and secretory activities of cultured human placental cytotrophoblast.

Ultrastructural, autoradiographic, immunofluorescent and biochemical techniques were used to characterize primary cultures of term placental cytotrophoblast in order to gain insight into the differentiation and secretory capacities of the cellular component of human trophoblast. Trypsin treatment of placental villi allowed isolation of a predominantly cytotrophoblast cell population that maintained viability up to 13 weeks in monolayer culture. Autoradiographic studies of tritiated thymidine incorporation identified a smaller diameter mononucleated cell population that was mitotically active and developed into larger diameter mononucleated cells and into multinucleated cells during culture. Ultrastructurally, cultured cells formed desmosomes, had an extensive network of cytoplasmic microfilaments and contained the organelles for hormone synthesis and secretion. These cells secreted steroid hormones, secreted Schwangerschafts protein I, actively incorporated tritiated glycoprotein precursors and expressed surface immunoreactivity for the beta-subunit of human chorionic gonadotrophin (hCG). However, medium concentrations of hCG and human placental lactogen dropped rapidly to undetectable levels after 14 days in primary culture. Cells grown beyond confluence differentiated into 1 to 2 mm structures with a villus-like histology. Our studies indicate that cytotrophoblast can secrete steroids, cytotrophoblast differentiation occurs in vitro in the absence of maternal tissues, hCG synthesis occurs in cultured cytotrophoblast and medium concentrations of placental protein hormones are not the best indicators of cell viability for cultures of cytotrophoblast.

Application of direct cannulation and injection lymphangiography to the study of the canine cardiac and pulmonary efferent mediastinal lymphatics.

Lymphangiograms of canine cardiac and pulmonary efferent mediastinal lymphatics were made by cannulation and injection of Ethiodol. Injections were made singly and serially. The mediastinal lymphatics and lymph nodes, which constitute the pathways of drainage of the heart and lungs, were delineated from the point of cannulation to the right and left inferior cervical region where the right lymphatic duct and thoracic duct are located. Lymphangiography reveals that the lymphatics which drain the heart and lungs may join to form common mediastinal lymphatic channels. Interconnections between mediastinal channels were demonstrated. The lymphatics terminated in the region of both the right lymphatic duct and thoracic duct in every subject. The so-called "cardiac node of Drinker" is usually a group of pretracheal nodes rather than a single node. The pretracheal nodes and those more cephalad receive drainage of lymph from both the heart and lungs. These studies suggest that lymph collected by cannulation of a "cardiac" lymphatic adjacent to the "cardiac node" will contain pulmonary as well as cardiac lymph. Thus the high flows reported by many investigators for "cardiac" lymph probably indicates that pulmonary lymph is mixed with cardiac lymph, and that the experimental data should be interpreted with this in mind.

Microwave exposure alters the expression of 2-5A-dependent RNase.

The effects of 2.45-GHz continuous-wave microwaves (SAR = 130 mW/g) on the expression of the interferon-regulated enzymes 2'-5'-oligoadenylate (2-5A) synthetase(s) and 2-5A-dependent endoribonuclease (RNase L) were studied in murine L929 cells. Cells growing as monolayers were removed from the substratum and placed in suspension culture for a 4-h sham or microwave exposure. The cells were returned to monolayer growth for 18 h, and then harvested and assayed to determine the amount of RNase L protein (via [32P]2-5A binding) and the specific activities of RNase L and 2-5A synthetase. Binding of radioactive 2-5A to RNase L for sham- and microwave-exposed samples was 14.5 and 36.4% above control, respectively (the microwave-exposed bound 19.0% more probe than the sham-exposed). The increases in 2-5A binding were accompanied by corresponding elevations of RNase L specific activity. In contrast, sham or microwave irradiation produced no alterations in 2-5A synthetase specific activity. No detectable differences were noted in the postexposure cell viability, plating efficiency, or proliferation rate. Also, there were no detectable differences in cell viability or plating efficiency between controls and cultures irradiated for 2 h when the temperature was simultaneously increased to above normal physiological limits (39 to 45 degrees C). The SAR (130 mW/g) and the power density (95 mW/cm2) used for the greater part of this study were nearly 20 times higher than the ANSI limit of 8 mW/g and 5 mW/cm2 for any 1 g of exposed human tissue.

Whipple's procedure plus intraoperative pancreatic duct occlusion for severe chronic pancreatitis: clinical, exocrine, and endocrine consequences during a 3-year follow-up.

The present investigation provides follow-up data (up to 36 months) of exocrine and endocrine pancreatic function, inflammatory activity, pain, and body weight in 23 chronic pancreatitis patients submitted to Whipple's procedure plus intraoperative Ethibloc occlusion of the remaining pancreatic duct system between January 1983 and February 1984. Clinically, Whipple's procedure plus intraoperative pancreatic duct occlusion resulted in almost complete and continuous cessation of pain as well as significant (p less than 0.05) increase in body weight. With regard to exocrine pancreatic function (Secretin-Pancreozymin test, plasma amino acid consumption test, Pankreolauryl test, fecal chymotrypsin determination), intraoperative pancreatic duct occlusion was shown to induce high-grade insufficiency and thus exocrine parenchymal atrophy in all patients. Simultaneously, the inflammatory process (represented by serum levels of trypsin, lipase, and pancreatic isoamylase) was terminated in all 23 patients. Endocrine pancreatic function, evaluated by serum levels of insulin and C-peptide measured under fasting conditions and subsequent maximal combined beta-cell stimulation as well as corresponding integrated hormone releases, was reduced by partial pancreas resection by about 50%, while there was no further impairment during the 36-month follow-up period in consequence of additional intraoperative pancreatic duct occlusion. Altogether, Whipple's procedure plus intraoperative Ethibloc occlusion of the residual pancreatic duct system seems suitable for termination of the inflammatory process and thus preservation of residual endocrine pancreatic function in chronic pancreatitis.

Role of octreotide in the prevention of postoperative complications following pancreatic resection.

Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

Active immunity and T-cell populations in pigs intraperitoneally inoculated with baculovirus-expressed transmissible gastroenteritis virus structural proteins.

The intraperitoneal inoculation of pigs with baculovirus-expressed transmissible gastroenteritis virus (TGEV) structural proteins (S, N, M) in conjunction with thermolabile Escherichia coli mutant toxin (LT-R192G) in incomplete Freund's adjuvant (IFA) was tested in an attempt to elicit active immunity to TGEV in gut-associated lymphoid tissues (GALT). Four groups of 63 (1-5-week-old) suckling, TGEV-seronegative pigs were used to assess the efficacy of the recombinant protein vaccine (group 3) in comparison with sham (group 1), commercial vaccine (group 2), and virulent TGEV Miller-strain-inoculated pigs (group 4). The TGEV-specific mucosal and systemic immune responses were measured after in vivo and in vitro stimulation with TGEV-antigens. The major T-cell subset distribution was analyzed in vivo and in vitro after stimulation of mononuclear cells with TGEV (from mesenteric lymph nodes of group 3 inoculated with TGEV-recombinant proteins). Induction of active immunity was assessed by challenge of pigs with virulent TGEV at 27 days of age. Baculovirus-expressed TGEV proteins coadministered with LT-R192G in IFA induced mesenteric lymph node immune responses associated with IgA-antibodies to TGEV and partial protection against TGEV-challenge. The high titers of serum IgG- and virus-neutralizing-antibodies to TGEV in group 3 pigs most likely reflected the dose of TGEV S-protein administered. At the day of TGEV-challenge, the in vitro stimulation of mononuclear cells from the mesenteric lymph nodes of group 3 pigs with inactivated TGEV resulted in an increase in double positive (CD4+CD8+), natural killer (CD2+CD4-CD8+dim) and cytotoxic (CD2+CD4-CD8+bright) T-cell phenotypes, accompanied by increased expression of interleukin-2 receptor and a decrease of the null (CD2-CD4-CD8-/SW6+) cell phenotype.