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.

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.

Cold acclimation or grapeseed oil feeding affects phospholipid composition and mitochondrial function in duckling skeletal muscle.

The phospholipid fatty acid (FA) composition and functional properties of skeletal muscle and liver mitochondria were examined in cold-acclimated (CA, 4 degrees C) ducklings. Phospholipid FA of isolated muscle mitochondria from CA birds were longer and more unsaturated than those from thermoneutral (TN, 25 degrees C) reared ducklings. The rise in long-chain and polyunsaturated FA (PUFA, mainly 20:4n-6) was associated with a higher State 4 respiration rate and a lower respiratory control ratio (RCR). Hepatic mitochondria, by contrast, were much less affected by cold acclimation. The cold-induced changes in phospholipid FA profile and functional properties of muscle mitochondria were reproduced by giving TN ducklings a diet enriched in grapeseed oil (GO, rich in n-6 FA), suggesting a causal relationship between the membrane structure and mitochondrial functional parameters. However, hepatic mitochondria from ducklings fed the GO diet also showed an enrichment in long-chain PUFA but opposite changes in their biochemical characteristics (lower State 4, higher RCR). It is suggested that the differential modulation of mitochondrial functional properties by membrane lipid composition between skeletal muscle and liver may depend on muscle-specific factors possibly interacting with long-chain PUFA and affecting the proton leakiness of mitochondrial membranes.

[Rapunzel syndrome, an rare form of intestinal trichobezoars]. / Das Rapunzel-Syndrom, eine ungewöhnliche Form intestinaler Trichobezoare.

Rapunzel syndrome is a rare cause of intestinal trichobezoar. Especially adolescent girls with uncharacteristical abdominal symptoms as well as weight loss and trichophagia are affected. The symptoms are caused by large amounts of swallowed hair within the stomach which can extend far into the intestinuum. Beside conventional radiology and sonography the diagnostic procedure of choice is endoscopy. If endoscopic removal of the bezoar fails surgical intervention is mandatory. As many of these patients show emotional disorders psychiatric evaluation and treatment has to be done to prevent recurrence. We report on a 12 year old girl with a huge trichobezoar which completely filled the stomach and extended far into the small bowel. As the bezoar could not completely be removed by endoscopy the girl had to be treated by surgery.

Regional variation of white adipocyte lipolysis during the annual cycle of the alpine marmot.

During winter, hibernating animals rely on their lipid stores for survival. In vitro lipolytic activity of isolated adipocytes from gonadal and subcutaneous white adipose tissue (WAT) was studied in captive alpine marmots (Marmota marmota) at two different times of their yearly cycle. During the summer, when marmots were eating, adipocyte responsiveness and sensitivity to isoprenaline and noradrenaline were higher in gonadal than in subcutaneous WAT. During hibernation, when marmots were spontaneously fasting. both the response and sensitivity to catecholamines decreased in gonadal WAT to the level of subcutaneous WAT. A similar pattern of response was also observed when lipolysis was stimulated with glucagon but the lipolytic rate was three times lower than with catecholamines. Adenosine deaminase (ADA) had a marked stimulatory effect on lipolysis, especially during the 'feeding' period, suggesting that adenosine may be a potent lipolytic modulator in marmot adipocytes. It is concluded that in marmots, lipolysis could be differentially regulated between fat depots during the annual cycle possibly to optimize either the building-up or the use of fat reserves.

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.

A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy.

A prospective, randomized, double-blind, multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137 evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection, usually beginning within 48 h after completion of chemotherapy. With the exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with sargramostim, there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors. Although the study was not designed to evaluate efficacy directly, there also were no statistically significant differences between treatment groups in total days of growth factor therapy, days of hospitalization, or days of i.v. antibiotic therapy during the treatment period. Both sargramostim and filgrastim were comparably well tolerated when given by s.c. injection in this group of patients, and no clinically significant differences between the growth factors were demonstrated.

Embryotoxicity induced by alkylating agents: 9. Low dose prenatal-toxic risk estimation of ethylmethanesulfonate based on no-observed-adverse-effect-level risk factor approach, dose-response relationships, and molecular dosimetry.

Analogously to an earlier study using methylnitrosourea (MNU) the prenatal-toxic risk of low doses of ethylmethanesulfonate (EMS) was estimated using different procedures, comparatively. First, the risk of low doses was estimated using linear extrapolation to zero. When using the variable "all gross structural abnormalities" the lowest effective dose in the experiment was 150 mg/kg body wt (5.6% incidence), the additional risk over background was calculated to be 5.0%, and the hypothetical incidence 0.1% was associated with the dose 3 mg/kg EMS. When evaluating "gross structural limb abnormalities," which are not observed in controls, the dose associated with the hypothetical incidence 0.1% was 17.4 mg/kg EMS. Furthermore, derived from a dose-response study of teratogenicity extrapolation to the possible risk of low doses was performed using nonlinear mathematical models. In this case, the results obtained are dependent on the dose response variable as well as from the statistical approach which was chosen. As an example, the values obtained from one evaluation are given: all gross structural abnormalities, Weibull transformation, jackknife approach: ED0.1% = 72 mg/kg EMS. For comparison a "virtually safe dose" was calculated by use of the no-observed-adverse-effect-level (NOAEL) risk factor approach. The NOAEL under our experimental conditions was 100 mg per kg body wt. By using an arbitrarily chosen risk factor of 100 a "safe dose" of 1 mg EMS per kg body wt was obtained. In addition, molecular dosimetry of the DNA adduct rate of O6-ethylguanine in the 11-day-old embryos was used. Based on the assumption that a linear correlation exists between this specific adduct rate and the incidence of teratogenic effects, the hypothetical incidence of 0.1% was associated with a dose of 99 mg/kg EMS. This value is quite similar to that obtained by extrapolation using probit analysis which is in contrast to the results obtained with MNU.

The influence of portoenterostomy with stoma on morbidity in pediatric patients with biliary atresia undergoing orthotopic liver transplantation.

A portoenterostomy (PE) procedure for extrahepatic biliary atresia (EHBA) is sometimes performed with a stoma in an attempt to reduce the incidence of acute cholangitis. The purpose of this study was to determine if the presence of a stoma increased the complication rate of patients undergoing orthotopic liver transplantation (OLT) for EHBA. The medical records of 42 consecutive patients with EHBA who underwent primary OLT between October 1988 and October 1991 were retrospectively reviewed. Three patients were excluded, since their grafts were lost within 3 days of OLT. The remaining 39 patients were divided into three groups: no PE (n = 7), PE without stoma (n = 23), and PE with stoma (n = 9). The mean age of the whole group was 19.62 +/- 24.37 months, with a range of 5 to 132 months. Mean weight was 9.62 kg, with a range of 4.2 to 41 kg. Survival at 3 and 12 months as well as number of retransplantations were similar among the three groups. However, at the time of OLT increased morbidity was observed, consisting of increased operative time and number of reoperations, whether or not the stoma had been closed prior to OLT.

Embryotoxicity induced by alkylating agents: 7. Low dose prenatal-toxic risk estimation based on NOAEL risk factor approach, dose-response relationships, and DNA adducts using methylnitrosourea as a model compound.

Prenatal-toxic risk estimation for the alkylating model compound methylnitrosourea (MNU) was performed using different procedures. Risk of low doses was estimated using linear extrapolation to zero (estimated ED0.1%: 0.1 mg/kg body wt MNU) as well as extrapolation by probit analysis based on a dose-response study (estimated ED0.1%: 1.6 mg/kg body wt). Furthermore, a "virtually safe dose" was established by means of the NOAEL risk factor approach (e.g., factor 30:0.03 mg MNU per kg body wt). In previous studies in murine embryos using MNU, we combined dose-response data and DNA adduct rate measurements and deduced that O6-methylguanine is a suitable variable for molecular dosimetry. In a tentative approach, we estimated the teratogenic risk of low doses based on the adduct rates of O6-methylguanine in the DNA of the embryos. It is concluded that in the case of steep dose-response relationships, which are typical for the majority of teratogenic effects, the NOAEL risk factor approach is more conservative than extrapolation based on probit analysis. Risk estimation using dosimetry with this model compound yields estimated incidences similar to linear extrapolation.

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.

Maximal stimulation of pancreatic islet B-cells, and A-cell response to arginine, in dogs with longterm pancreatic acinar atrophy.

The response of the pancreatic islet A- and B-cells after long-standing (eight years) pancreatic duct occlusion by prolamine, and subsequently developed acinar atrophy, was studied in five beagles, and the results compared with those in six sham-operated dogs. Intravenous arginine infusion (A-cell stimulation) and a combined oral glucose and intravenous tolbutamide and glucagon infusion (B-cell stimulation) were carried out in each dog. Complete abolition of acinar function after duct occlusion was documented by the negative paraaminobenzoic acid test. In contrast, in plasma, baseline values of glucose, alpha-amino-nitrogen, insulin, glucagon, glucagon-like immunoreactivity, somatostatin-like immunoreactivity, and pancreatic polypeptide did not differ between the experimental groups. During B-cell stimulation dogs with occluded ducts had significantly reduced insulin, reduced glucagon, and reduced second phase pancreatic polypeptide compared with controls. Integrated insulin and pancreatic polypeptide were also reduced in dogs with occluded ducts. In both groups plasma and integrated values of glucose and somatostatin-like immunoreactivity did not differ. During the A-cell stimulation period dogs with occluded ducts had significantly raised alpha-amino-nitrogen but unchanged glucose and reduced insulin concentrations; in both groups the arginine-induced rise in glucagon was similar, although it was delayed in the experimental group. In the latter, integrated alpha-amino-nitrogen was raised, but integrated glucose and hormones were unchanged. We conclude that a previously intact dog pancreas that has been atrophied by duct occlusion, may be able to maintain euglycaemia for several years. There may be a complex interplay of changes induced by duct occlusion at the level of the pancreatic islets and elsewhere, which compensate for moderate insulinopenia.

Delineation of electric and magnetic field effects of extremely low frequency electromagnetic radiation on transcription.

The relative effects of the electric and magnetic field components of extremely low frequency electromagnetic radiation (ELF) on transcription were examined in human leukemia HL-60 cells. Delineation of the individual field contributions was achieved by irradiating cells in separate concentric compartments of a culture dish within a solenoid chamber. This exposure system produced a homogeneous magnetic field with a coincident electric field whose strength varied directly with distance from the center of the culture dish. Irradiation of HL-60 cells with sine wave ELF at 60 Hz and a field strength of 10 Gauss produced a transient increase in the transcriptional rates which reached a maximum of 50-60% enhancement at 30-120 minutes of irradiation and declined to near basal levels by 18 hours. Comparison of transcription responses to ELF of cells in different concentric compartments revealed that the transcriptional effects were primarily the result of the electric field component with little or no contribution from the magnetic field.

Cholecystokinin and glucose-induced insulinaemia in dogs with and without pancreatic acinar atrophy.

The entero-insular hormonal axis was studied in eleven conscious Beagle dogs, loaded with glucose orally and intravenously. In five of them, exocrine pancreatic atrophy was induced by pancreatic duct occlusion with prolamine, and documented by means of the p-amino-benzoic acid test. After oral glucose, the duct-occluded dogs displayed higher blood glucose (log area 4.12 +/- 0.07 versus 3.76 +/- 0.10; p less than 0.01), less plasma insulin (log area 3.56 +/- 0.08 versus 3.99 +/- 0.08; p less than 0.01) and less cholecystokinin-like immunoreactivity (log area 2.64 +/- 0.09 versus 3.10 +/- 0.14; p less than 0.01) than controls. In controls, the peripheral venous insulin concentrations were higher after oral than after isoglycaemic intravenous glucose, and this difference was no longer demonstrable in duct-occluded dogs. In the latter, gel permeation chromatography of pool plasma after oral glucose revealed a relative decrease of cholecystokinin-like immunoreactivity species, which eluted at the positions of sulphated cholecystokinin octapeptide, cholecystokinin-33 and cholecystokinin-39, and at a position intermediate between these two. Also in the duct-occluded animals, intravenous infusion of sulphated cholecystokinin octapeptide, in addition to oral glucose, resulted in an increase in plasma insulin (log area 3.83 +/- 0.10 versus 3.64 +/- 0.06; p less than 0.01) and an improvement in oral glucose tolerance. It is concluded that in the dog 1) the absence of pancreatic acinar tissue is associated with a loss of gastrointestinal factors mediating glucose-induced insulin secretion, and 2) reduction of circulating endogenous cholecystokinin species may account at least in part for this defect.

[Surgical treatment of radiogenic prostate-urethra-rectum fistula]. / Chirurgische Therapie radiogener Prostata-Harnröhren-Rectumfisteln.

Five patients with postirradiation prostatic urethrorectal fistules after treatment of localized carcinoma of the prostate by external beam and interstitial implantation with 125I seeds were treated by two different methods. Previous defunctioning colostomy and suprapubic tube diversion alone failed to close the lesion. Three patients underwent anterior rectal resection and restoration by deep colo-anal anastomosis. Two more patients were treated by anterior "pull-through-resection" with mucosectomy of the distal rectal stump and colo-anal sleeve anastomosis as described by Parks. In addition, omentum was used to fill the pelvis. This operative technique is favoured due to improved results.

[General environmental pollutants and passive smoking]. / Allgemeine Umweltnoxen und Passivrauchen.

Epidemiological studies-especially data from smog episodes-indicate that antropogenous outdoor air pollution exercises a deleterious effect on health and particularly on the respiratory organs. Controlled exposure test in animals and man confirm this. The main pollutants are SO2, suspended dust particles (dust aerosols or solid atmospheric condensation nuclei) as well as NO2 (NOx) and O3. The adverse influence of quite a number of meteorological factors such as low temperature and inversion cannot be denied. During smog conditions in January 1985 in the Federal Republic of Germany there was a highly significant negative correlation between atmospheric temperature and the rate of exacerbations of bronchitis. Indoor air pollution is gaining in importance. Airtight sealing of buildings associated with reduced indoor ventilation results in novel health upsets ("sick building syndrome"). Interiors are characterised by an accumulation of CO2, CO, NO2, dust aerosols and various organic substances such as benzene, benzypyrene, formaldehyde, nitrosamines etc. Cigarette smoke is a frequent cause of indoor air pollution. The possible unhealthy effects of passive smoking (mainly the inhalation of sidestream smoke) have been frequently studied. Infants of smoking parents are more often affected by respiratory diseases than non-exposed children. The same applies to schoolchildren: the incidence of bronchial signs and symptoms increases with increasing smoke consumptions of the parents. However, no definitely established effect on lung function has been seen in children, adults and asthmatics. The important question as to whether passive smoking increases lung cancer risk is still a subject of controversial discussion among experts.

Severe chronic cephalic pancreatitis: use of partial duodenopancreatectomy with occlusion of the pancreatic duct in 289 patients.

Partial duodenopancreatectomy and occlusion of the remaining ductal system by Ethibloc to induce rapid exocrine atrophy for treatment of severe chronic cephalic pancreatitis was introduced in our department in January of 1978. Since then, this surgical procedure has been performed in a total of 289 patients. Postoperative morbidity was 12.2%, 5 pancreatic and 3 biliary fistulas occurred. Postoperative mortality was 1% and relapses of pancreatitis occurred in only 2.2% due to incomplete filling of ducts with Ethibloc. A total of 88.2% of patients became pain-free and symptomless, 10.8% voiced minor complaints, and 85.9% gained an averaged of 7.8 kg weight postoperatively. We conclude that Ethibloc occlusion is highly effective in inducing complete exocrine atrophy, thus abolishing the inflammatory process and preventing relapses of chronic pancreatitis and preserving the endocrine function from further impairment. This was demonstrated by biochemical assays during a 36-month follow-up in a prospective study in 23 of 289 patients. Our results compare favorably with and are superior to results from any other operative procedure for chronic cephalic pancreatitis. We consider partial duodenopancreatectomy combined with Ethibloc occlusion of the pancreatic duct the procedure of choice in the surgical treatment of severe chronic cephalic pancreatitis.