Different susceptibilities of the urinary bladder epithelium of animal species to three nitroso compounds. Differences in the susceptibilities of the urinary bladder epithelium of Wistar rats, ICR mice, Syrian golden hamsters, and Hartley guinea pigs to three N-nitroso compounds, N-butyl-N-(4-hydroxybutyl)nitrosamine, N-ethyl-N-(4-hydroxybutyl)nitrosamine, and N-butyl-N-(3-carboxypropyl)nitrosamine, were examined histologically. The urinary bladder epithelium of rats was the most susceptible to all three compounds, and especially to N-ethyl-N-(4-hydroxybutyl)nitrosamine, and bladder cancers developed in all the rats given this compound. The bladder epithelium of mice was less susceptible than that of rats but, although the incidence of cancer was lower than in rats, that of cancer with invasion was higher. Hamsters were far less susceptible than mice, and cancer developed only in 3 of 41 animals given N-ethyl-N-(4-hydroxybutyl)nitrosamine. Guinea pigs were the least susceptible of the 4 species and no tumors were found. Hisotlogically, most of the tumors induced in rats and mice were transtitional cell carcinomas. The incidence of undifferentiated carcinoma was higher in mice than in rats and cellular or structural atypism of the cancer was also greater in mice. Cancers induced in hamsters were all transitional cell carcinomas showing invasion.


Antitumor activity of degraded products of lentinan: its correlation with molecular weight. Lentinan, an antitumor polysaccharide from Lentinus edodes, was degraded to seven fractions by treatment with formic acid. The low molecular-weight fractions (I and II) showed no antitumor activity against sarcoma-180 solid-type tumor and the absorption maximum of Congo Red did not shift in their presence in 0.1M sodium hydroxide. The medium molecular-weight fraction III, which required the increase of doses (5 or 10 mg/kg) for inhibition of tumor growth, caused a little shift. On the other hand, the absorption maximum of Congo Red shifted largely by the presence of high molecular-weight fractions (IV approximately VII) which showed the inhibition ratio of over 95% in a dose of 1 mg/kg. Participation of molecular weight in the antitumor activity of polysaccharides which contain (1 leads to 3)-beta-D-glucan main chain was discussed.


Effect of plastic bead on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine. Experiments were made on induction of cancer of the glandular stomach of rats by a combination of oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and insertion of a plastic bead into the gastric lumen. The incidence of cancer with this combination of treatments was greater than by administration of MNNG alone. Fluoroscopic examination showed that barium sulfate remained in the stomach longer when a bead had been inserted into the gastric lumen. This indicates that after insertion of a bead, MNNG must have remained in the stomach longer, and so the period of exposure of the gastric mucosa to the carcinogen must have increased.


Effect of drug combination of antitumor activity and myelotoxicity. Relationship between the survival time of L-1210-bearing mice and myelosuppression of normal mice after combination chemotherapy was studied. In a variety of combinations of 6-mercaptopurine, 6-thioguanine, and cyclophosphamide, a combination of cyclophosphamide and 6-thioguanine produced the highest increase in life span (ILS) and the highest number of 60-day survivors of all. In contrast, a combination of 6-mercaptopurine and 6-thioguanine showed as low as ILS as did single agents. A combination of 6-mercaptopurine, cyclophosphamide, and 6-thioguanine exhibited the second best effect on survival time of leukemic mice. However, in myelosuppression as measured by changes in the total number of nucleated cells, in the number of hematopoietic colony-forming cell, and in peroxidase level of femoral bone-marrow, the combination of 6-mercaptopurine and 6-thioguanine showed no more toxicity than the other 2-drug combinations. In addition to these findings, the presence of a striking difference in the cell number in ascitic fluid of leukemic mice among the animals given 6-thioguanine, and those given other 2- or 3-drug combinations may suggest that the difference in the antileukemic activity is not due to the difference in the toxicity against the host, but due to the difference in the activity of direct action of combined drugs on leukemic cells in the peritoneal cavity or in other sites.


Protective effect of mucin on experimental gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine plus sodium chloride in rats. Studies were made on the effect of mucin on the induction of gastric carcinomas by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), with or without sodium chloride, in male Wistar rats. Seven groups of rats were treated as follows: Group 4 was given continuously 50 mg MNNG/liter solution to drink and 1 ml of saturated sodium chloride once a week and fed on stock diet supplemented with 4% mucin. Group 2 was given 50 mg MNNG/liter solution and fed on stock diet supplemented with 4% mucin. Group 3 received 1 ml of saturated sodium chloride once a week and 50 mg MNNG/liter solution to drink. Group 1 was treated with MNNG only. Group 5 was fed on stock diet supplemented with 4% mucin. Group 6 was given sodium chloride only. Group 7 was untreated. The incidence of gastric cancer in Group 3 was significantly higher than that in Group 4 (P less than 0.05) or in Group 1 (P less than 0.05). The difference in the incidence of gastric cancer in Groups 2 and 4, and of intestinal tumors in Groups 1 to 4 were not statistically significant. No malignant tumors were seen in Groups 5, 6, and 7. Thus mucin reduced the high incidence of gastric cancer induced by MNNG and sodium chloride to the level induced by MNNG alone, but it had no effect on the incidence of intestinal tumors. The effect of mucin in preventing destruction of the gastric mucosal barrier by sodium chloride and so reducing the induction of gastric cancer is discussed.


Carcinogenic effect of N-butyl-N-nitrosourethan on CDF1 mice. Studies were made on the induction of tumors in mice by N-butyl-N-nitro-sourethan (BNUR), with the following results. 1) Oral administration of 0.04% BNUR in deionized water to CDF1 mice for 20 weeks produced papillomas in the esophagus and forestomach of all 58 mice, and 24 of the mice had squamous cell carcinoma. 2) No skin tumors developed when 0.1%, 0.5%, or 1% BNUR in acetone was painted on the skin on the back of CDF1 mice three times a week for 25 weeks. 3) No sarcomas developed within 30 weeks when a dose of 10, 60, or 120 mg/ml of BNUR in dimethyl sulfoxide solution was injected subcutaneously into the back of CDF1 mice, 10 times at 1-week intervals. 4) In the in vitro malignant transformation test, golden hamster lung fibroblast cells did not show malignant transformation during an observation period of 150 days after treatment with BNUR at a final concentration of 30 and 60 mug/ml for 24 hr. The carcinogenicity and possible mode of action of BNUR are discussed on the basis of these results.


Leiomyosarcomas of the small intestine induced in dogs by N-methul-N'-nitro-N-nitrosoguanidine. Leiomyosarcomas of the small intestine were found in dogs during experimental induction of gastric carcinoma by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Leiomyosarcomas were found most frequenly in the duodenum and jejunum, and occasionally in the stomach but never in the ileum, colon, or rectum. The leiomyosarcomas developed in all the dogs given 50 mug/ml of MNNG in deionized water to drink but not in dogs fed on porridge food made from standard pellet diet mashed with MNNG at the same concentration in tap water. Intestinal sarcomas developed in 3 months to 5 years after the end of MNNG administration, and frequently metastasized to the liver and/or the peritoneum.


Mechanism of suppressive effect of basic cupric acetate on rat liver carcinogenesis by ethionine. The rate of ethylation of t-RNA in vivo by L-ethionine[ethyl-1-14C] markedly lowered in the liver of rats fed a diet containing copper than that of control. In corporation of the labeled compound into the t-RNA of liver by a single injection. of L-ethionine[ethyl-1-14C] was inhibited as much as 50% by the preceding concurrent administration of copper and ethionine added in the diet to rats. Direct interaction of copper ion with ethylation by ethione in the specific t-RNA of the rat liver was examined as an important biochemical explanation in molecular level for the inhibitory mechanism of copper on rat liver carcinogenesis by ethionine. Profiles of normal t-RNA on methylated albumin-kieselguhr column chromatography revealed three components for leucine, two of which were found at the tube number 40 to 50 and disappeared in the leucyl t-RNA treated with ethionine. The components for leucine that disappeared were normalized in the liver of rats by the concurrent administration of copper.


Complete regression of Ehrlich solid tumors by the combined administration of glucose, wheat straw hemicellulose-B, and ovoglycopeptide. Glucose solution containing wheat straw hemicellulose-B and ovoglycopeptide (W-O-G) has no effect on Ehrlich ascites tumors but completely regresses Ehrlich solid tumors. The carcinostatic effect of this mixture is lost or decreases markedly whenever one of the three substances is lacking. For this glucose solution to possess a carcinostatic effect it is necessary that this hemicellulose-B of W-O-G is the hydrolysate of the extract with 20% NaOH from the residue obtained after extraction of wheat straw with 10% NaOH.


Induction of transplantation immunity by dansylated tumor cells. Tumor cells were coupled with fluorecent dansyl group in aqueous medium by dansyl chloride-cycloheptaamylose complex (CDC) without destruction of the cells. C57BL/6 mice and Donryu rats pretreated respectively with dansylated EL4 leukemia cells and with dansylated Yoshida sarcoma cells acquired transplantation immunity to the corresponding tumor cells. Serum and spleen cells obtained from EL4 immune mice showed cytotoxicity to EL4 cells but not to other allogeneic leukemia cells. Hapten-specific cytotoxicity of immune serum and spleen cells was not observed in the present immune system.


Antitumor activity of berberrubine derivatives. The antitumor activity of berberine, berberrubine, and their derivatives against sarcoma-180 ascites was determined by the total packed cell volume method. Berbine and tetrahydroberberine derivatives had no antitumor activity, but berberrubine (9-demethylberberine) and the ester derivatives of berberrubine had a strong antitumor activity. ED90 of berberrubine, its acetate and benzoate, were 15, 23, and 44 mg/kg, respectively. The therapeutic indices (LD10/ED90 by the present method) of these compounds were as follows: Berberrubine hydrochloride, 6.7 approximately 9.4; 9-acetyl-9-demethylberberine (9-acetylberberrubine) chloride, 7.6 approximately 8.7; 9-benzoyl-9-demethylberberine (9-benzoylberberrubine) chloride, 3.4 approximately 4.9.


Combined effect of cyclocytidine and lentinan of spontaneous mammary tumors in mice. Cytotoxic cytidine analog, cyclocytidine, and antitumor immunopotentiator, lentinan, offered an opportunity of testing the effect of combined modality of cytocidal agent and immunopotentiator on spontaneous mammary tumors of mice. Lentinan did not improve the therapeutic effect of cyclocytidine; it only prevented the early toxic death of mice due to cyclocytidine in one strain of mice but not in the other strain.


Colonic perforation in Crohn's disease.

Colonic perforation in Crohn's disease. Three cases of acute, free perforation of the colon in Crohn's disease are described and their clinical and pathological features are detailed. Colonic perforation in Crohn's disease bears no definite relationship to obstruction or adrenocorticosteroid therapy. It may occur with or without toxic megacolon, and pathological study has not thus far suggested a common pathogenetic mechanism. Although free perforation has been considered to be extremely rare in Crohn's colitis, it is likely that this complication is more common than previously believed.


Candida esophagitis: a prospective study of 27 cases. A prospective study of candida esophagitis was undertaken to determine the spectrum of this disease in a general hospital. During 1 year, in 370 consecutive endoscopies, 27 patients with Candida esophagitis were detected. The diagnosis was established by finding white plaques on endoscopy, yeast organisms on microscopic examination of a direct smear from the plaques, and a serum agglutinin titer of at least 1:160. Of these 27 patients, 14 had esophageal symptoms. Twelve patients were reendoscoped after nystatin or nystatin and flucytosine therapy. Nine patients showed absence of lesions, a negative smear, and disappearance of symptoms. Control patients had no plaques on endoscopy, no yeast organisms on microscopical examination of esophageal brushings, and a positive titer in 4 to 17% of cases. A minimal agglutinin titer of 1:160 was found in 4 to 12% of two additional groups on controls. Absence of titer precluded a diagnosis of Candida esophagitis.


Antral gastrin concentration in patients with vagotomy and pyloroplasty. Antral gastrin concentration was measured in endoscopic forceps biopsy specimens and prepyloric mucosa in patients with vagotomy and pyloroplasty, duodenal ulcer patients and nonulcer patients. Antral gastrin concentration in vagotomy and pyloroplasty patients, 35.5 +/- 4.1 ng of gastrin per mg of tissue (mean +/- SEM), was significantly greater (P less than 0.01) than antral gastrin concentration in duodenal ulcer patients, 13.0 +/- 2.4 ng per mg, and antral gastrin concentration in controls, 14.8 +/- 3.1 ng per mg. Basal and meal-stimulated serum gastrin levels in vagotomy and pyloroplasty patients were also significantly greater (P less than 0.05) than gastrin levels in either duodenal ulcer patients or controls. Acid secretion rates were not significantly correlated with serum or antral gastrin concentrations in the patients groups.


Absorptive and digestive function of the jejunum after jejunoileal bypass for treatment of human obesity. Rates of absorption of leucine, glycylleucine, and glucose, and rates of hydrolysis of maltose were determined in the jejunum of a group of obese persons before and at intervals (between 2 and 20 montsh) after jejunoileal bypass for the treatment of obesity. The leucine absorption rate was significantly reduced after the bypass, but the absorption rates of glycylleucine and glucose as well as the hydrolysis rate of maltose were unchanged. Light microscopic investigation of the jejunal mucosa, obtained by a peroral biopsy technique before and at 7 months after by bypass operation, did not reveal any change in the histological appearance of this tissue. The plasma aminograms of all 7 patients were compared before and at intervals after the bypass operation; all exhibited a constant pattern of change that was characterized by significant decreases in the concentrations of serine and glycine and by significant decreases in the concentrations of valine, isoleucine, leucine, tyrosine, and phenylalanine. This pattern of change, which is characteristic of protein depletion, persisted during the entire period of observation. Two of these 7 patients developed laboratory evidence of hepatic dysfunction. It is concluded that (1) protein depletion is common to all patients with jejunoileal bypass with or without hepatic dysfunction; and (2) protein depletion results in a sustained reduction in free amino acid absorption in the jejunum.


Medical and surgical therapy in diverticular disease: a comparative study. The course of 132 patients with documented acute diverticulitis was analyzed: 99 patients treated medically and 33 patients treated surgically were followed for an average of 9.2 years. Seventy-three per cent of the medical group and 79% of the surgical group had no further symptoms or hospital admissions as a result of their diverticular disease once they were recovered from the acute episode. For three-quarters of the patients, therefore, acute diverticulitis occurred as a single episode that responded to either medical or surgical management. Considering the morbidity and cost to the patient, the treatment of the patient recovered from acute diverticulitis should be medical, with operation reserved for complications.


Effect of caffeine on the human small intestine. Methylxanthines produce intracellular accumulation of cyclic 3'5'-AMP (cAMP) by inhibition of phosphodiesterase and mucosal cAMP accumulation. Cyclic AMP is thought to mediate small intestinal secretion caused by some enterotoxins, hormones, and methylxanthines. These studies were designed to evaluate the effect of caffeine on small intestinal net fluid movement and transit times. The administration of caffeine in amounts ordinarily contained in many beverages and medications (75 to 300 mg) resulted in striking net secretion in the jejunum which lasted at least 15 minutes. This occurred in six of seven studies. Baseline net absorption of 0.5 ml per cm per hr was reversed to net secretion of 6.0 +/- 2.2 ml per cm per hr after oral caffeine ingestion (P less than 0.01). Net secretion also occurred in the ileum in seven of eight studies, but the onset of secretion appeared 35 min later than in the jejunum. These patterns of secretion correlated best with the passage of the intestinal bolus of caffeine rather than plasma caffeine levels. In contrast to other net secretory conditions, which increase the speed of transit, small intestinal transit times, as determined by dye dilution methods, were unchanged by caffeine. It is possible that methylxanthine-induced small intestinal secretion may play a role in the symptoms experienced by some patients with functional diarrhea.


Effect of intestinal hormones and peptides on intragastric pressure in dogs. Intragastric pressure was measured in dogs with gastric fistulas by using a flaccid balloon containing 500 ml of water. Intravenous infusion of cholecystokinin (20% pure), the carboxyl-terminal octapeptide of cholecystokinin, secretin, and vasoactive intestinal peptide produced dose-related decreases in intragastric pressure with maximal decreases of 40% or more. Glucagon and gastric inhibitory peptide produced smaller decreases in intragastric pressure. Motilin caused a dose-related increase in intragastric pressure that lasted only about 7 min despite continuing infusion of the peptide. The half-dose of cholecystokinin or of octapeptide of cholecystokinin for pancreatic protein secretion and the half-dose of secretin for pancreatic bicarbonate secretion each produced significant inhibition of intragastric pressure, suggesting that these hormones play a physiological reole in regulating gastric pressure.


Maturation and differentiation of cultured fetal stomach. Effects of corticosteroids, pentagastrin, and cytochalasin B. Gastric mucosa of fetal rats undergoes striking developmental changes during the last few days of gestation in utero. To investigate some aspects of this process, gastric explants from 18-day fetuses (4 days before birth) were maintained in organ culture for 3 days, then assessed by light and electron microscopy. The epithelia from base line uncultured stomachs were stratified and morphologically undifferentiated. During culture in basic medium (Leibovitz L 15), modest maturation of antral and fundic architecture occurred, characterized by epithelial invagination to produce small pit-glands. Secretory granules appeared in occasional epithelial cells, and cytochemistry indicated that most were mucous granules. Addition of pentagastrin (10(-9) to 2 X 10(-7) M) did not induce further morphological maturation in this system. However, addition of cortisol (10(-6) to 10(-5) M) resulted in a marked, dose-related increase of pit-gland formation and of cytological differentiation (appearance of secretory granules). This cortisol-induced architectural maturation was completely inhibited by the mold metabolite cytochalasin B (10(-5) M). The results indicate that fetal gastric maturation can be partially reproduced by culture in chemically defined media, and also suggest that corticosteroids may plan an important role in gastric organogenesis.


The effect of ischemic villus cell damage on crypt cell proliferation in the small intestine: evidence for a feedback control mechanism. In recent years the hypothesis that the number of villus cells regulates crypt cell proliferation in the epithelium of the small intestine has been brought forward by a number of investigators. To test this hypothesis, the villus cell population was reduced by clamping the superior mesenteric artery and vein in rats for 1 hr and the effects on the intestinal epithelium were studied during the first 24 hr. It was shown that temporary interruption of the blood flow to the small intestine led to a marked decrease in the number of functional villus cells within 2 hr; preferentially, cells from the upper part of the villus were lost and the number of crypt cells was not affected. This reduction in the number of villus cells led to an increase in the percentage of labeled crypt cells after pulse labeling with [3H]thymidine, and an expansion of the proliferative cell compartment in the crypt. After a peak of proliferative activity at 16 hr, the investigated crypt cell kinetic parameters approached control values after 24 hr, as did the number of villus cells. The enzyme activities of nonspecific esterase and neutral alpha-glucosidase showed marked decreases in isolated crypt and villus cell compartments as crypt cell proliferation increased. These data support the view that the feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the hypothesis of a feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the view that the feedback control of proliferation by the villus cells is a local control mechanism.


Post-transfusion chronic liver disease.

Post-transfusion chronic liver disease. To document the sequelae of acute hepatitis among recipients of commercial and volunteer blood and to assess factors influencing the development of chronic hepatitis (CH), 47 patients with post-transfusion hepatitis were followed prospectively from the time they received their transfusions. Twenty-nine had prolongation of at least 2-fold serum glutamic pyruvic transaminase (T) elevations for more than 20 weeks, and were classified as CH. When the patients with CH were compared to those with only acute hepatitis (abnormal T for less that 20 weeks), no difference was found with respect to age, sex, number of units transfused, incubation period, presence or absence of symptoms, occurrence of jaundice, maximum T, receipt or development of hepatitis B surface antigen or antibody, underlying illness, or area of the hospital where the patient was treated. Liver biopsies in 15 of the 29 revealed chronic-active hepatitis in 9, chronic persistent hepatitis in 2, unresolved hepatitis in 4. Five of the 9 patients with chronic active hepatitis were without symptoms. None of these died or have developed cirrhosis. Because chronic liver disease frequently developed after acute post-transfusion hepatitis among multiply transfused hepatitis B surface antigen negative blood recipients, close follow-up, including liver biopsy, is warranted in such patients with prolonged transaminase elevations.


Kinetics of [14C]cholic acid in fulminant hepatic failure: a prognostic test. The kinetics of intravenously injected [14C]cholic acid have been investigated in 14 patients with fulminant hepatic failure, 24 to 36 hr after the development of grade IV encephalopathy. Radioactivity was measured in plasma samples and in the individual plasma bile acid fractions after separation by thin layer chromatography. Plasma disappearance curves of the free [14C]cholic acid were calculated by an iterative nonlinear least squares fitting procedure using a computer. The disappearance of total plasma radioactivity was similar in all patients and greatly prolonged compared with healthy subjects. However, the plasma disappearance of free [14C]cholic acid was significantly faster in the 8 patients who recovered consciousness than in the 6 who did not. Plasma disappearance of free [14C]cholic acid correlated highly significantly with the proportion of conjugated [14C]cholate in plasma. All patients in whom more than 70% of plasma radioactivity was in the conjugated fraction 3 hr after injection survived and left hospital, whereas all of those in whom less than 55% was conjugated died. Measuring the percentage conjugation of [14C]cholate 3 hr after injection may therefore be a useful test of residual liver function in hepatic failure, as a guide to prognosis and in evaluating new forms of treatment.


Lincomycin-induced cholecystitis and gallstones in guinea pigs. Guinea pigs given lincomycin 60 mg per kg per day showed a striking increase in the renewal of epithelial cells in the gallbladder. This was detectable after only 24 hr of treatment. By 48 hr a precipitate consisting predominantly of calcium and bilirubin had formed in the gallbladder. Gallbladder bile glycoprotein concentrations rose progressively. At 8 days epithelial dysplasia was marked. Treatment was discontinued at 9 days. The guinea pigs that survived beyond 34 days showed that new tubuloalveolar glands had formed focally in the body and fundus of the gallbladder. Multiple calcium-containing stones were present. The failure to culture bacteria from bile, the failure of the bile salt pattern to change, and the progressive nature of the epithelial injury suggested that the changes resulted from a direct toxic effect and were not dependent on the antibiotic activity of this drug. It was concluded that damage to the epithelium of the gallbladder preceded the formation of a precipitate and initiated histological changes which culminated, at the time that the precipitate became organized into stones, in impressive glandular metaplasia.


Evaluation in dogs of cross-circulation in the treatment of acute hepatic necrosis induced by yellow phosphorus. The efficacy of cross-circulation in the treatment of acute liver failure has been evaluated in dogs. Four of 5 dogs administered a dose of yellow phosphorus that is lethal 90% of the time survived after treatment by cross-circulation of whole blood for between 1 and 8 hr with a normal dog. In 2 normal unmatched dogs plasma cross-circulations were performed over a period of 31 days without any clinical or laboratory manifestation of hypersensitivity except for lymphocytotoxic antibody titer rise. The results suggest that whole blood cross-circulation is effective and imply that a single donor could be utilized for prolonged periods of plasma cross-circulation with avoidance of immunological consequences of whole blood exchange.


Radioautographic observations of a 19-month-old ileal conduit. The influence of an altered environment of the cellular kinetics and histological appearance of ileal mucosa used as a urinary bladder was investigated in a patient with a conduit of 1 year and 7 months' duration. After injection of 10 mc of 3H-TdR, multiple biopsies were taken spanning a 3-day period. No increase in inflammatory cell numbers was seen and villous atrophy was minimal. A generation time or total cell cycle time of 36 hr was observed, with a G1 phase of 22 hr and an S phase of 11 hr. At 1 hr 2.4 3H-TdR-labeled cells per crypt column and a mitotic index of 1.4% were obtained. The complet labeled mitosis curve obtained on the epithelial cells of the 19-month-old ileal conduit mucosa demonstrated a retention of the kinetics and histological characteristics of normal ileal mucosa, contrary to previously documented findings.


Congenital hepatic fibrosis with dilation of intrahepatic bile ducts. A therapeutic approach. A case of congenital hepatic fibrosis with dilation of the intrahepatic ducts is presented. External drainage and lavage of the biliary tract through a prosthetic "Y" tube and internal drainage accomplished by a Roux en-Y cholangiojejunostomy resulted in prevention of the patient's recurrent bouts of cholangitis and sepsis. Surgical therapy for recurrent cholangitis in this disease is reviewed.


Acute suppurative cholangitis secondary to calcific pancreatitis. In the absence of calculi or carcinoma, the occurrence of acute suppurative cholangitis secondary to calcific pancreatitis is extremely rare. This report describes the successful management of acute suppurative cholangitis by surgical decompression and use of a new aminoglycoside, amikacin.


Dimensions of adolescent psychopathology and their prognostic significance for treatment outcome. The mothers of 87 male and female adolescents accepted at a counseling agency described their offspring by completing the Institute of Juvenile Research Behavior Checklist. A factor analysis of the initial data yielded nine symptom factors. These were used in combination with selected demographic variables, to compare the 54 continuers in treatment with the 22 early defectors and the 18 cases improved after a year of a full course of treatment with the 16 unimproved cases. Both discriminant function analyses indicated that the groups could be successfully differentiated; however, variables most predictive of continuance in treatment were not most predictive of a successful outcome.


Accelerated conservation acquisition and IQ gains by blind children. Because blind chidlren are retarded in the attainment of substance conservation and other Piagetial concepts, it was hypothesized that a learning set training procedure which incorporated both substance conservation and subordinate concepts might accelerate the acquisition of substance conservation itself and promote generalization to weight conservation scores and IQ. To test the hypotheses, 28 blind children aged 8 to 13 (IQ range 62 to 131) were divided into two groups. Their visual capacities ranged from 20/500 in the best eye to total congenital blindness and etiologies were varied, but consisted primarily of cataracts and glaucoma. All children were pretested and posttested on Slosson's Intelligence Test, 40 substance conservation tasks, and 20 weight conservation tasks, which involved both continuous and discontinuous substance and included almost all those found in the literature prior to 1970. A lengthy learning set procedure employing everyday household objects was then used to teach the experimental children conceptual skills that are prerequisites to substance conservation. Finally the learning set procedure was used to teach the concept of substance conservation itself to the children. The trained group exhibited significantly increased substance and weight conservation scores and IQs (all ps less than .005). The control group, which had spent matched periods of time in intellectual enrichment activities failed to improve significantly on any of the dependent variables. The research suggests that acceleration of the development of Piagetian concepts may be profitable enterprise in the case of blind children.


Factor VII levels as a guide to prognosis in fulminant hepatic failure. Levels of clotting factors II, V, and VII were measured on admission and then daily in 12 patients with grade IV hepatic coma due to fulminant hepatic failure. Factor VII levels obtained within 36 hours of the development of grade IV coma were not of value in predicting which patients would subsequently recover consciousness. Four of the latter group had levels below 9% at this time while the levels in three of the seven fatal cases were higher. Serial determinations were of more value and levels rose rapidly in those patients who ultimately made a complete recovery.


Focal nodular hyperplasia of the liver: a rational approach to treatment. Focal nodular hyperplasia of the liver in a 3 year old child has been successfully treated by ligation of the hepatic artery branches supplying the lesion. The prominence of the abnormal vasculature in the lesion and its possible aetiological involvement is stressed. Because of the risks of partial hepatectomy, hepatic artery ligation is suggested as the treatment of choice for focal nodular hyperplasia.


Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure. Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).


Intestinal perfusion studies in tropical sprue. 1. Amino acid and dipeptide absorption. Intestinal absorption of glycine 20 mmol/1, glycyl-glycine 10 mmol/1 plus L-leucine 10 mmol/1, and glycyl-L-leucine 10 mmol/1 has been studied by intestinal perfusion in 11 patients with tropical sprue and 10 control subjects. The patients with sprue had a significant reduction in the rate of absorption of glycine from a 20 mmol/1 solution, but there were no significant differences in the absorption of the other substances. The failure to demonstrate any difference in the absorption of these substances is probably related to their low concentration relative to the maximum absorptive capacity of the intestine. In both groups of subjects the kinetic advantage of glycyl-glycine absorption as compared with glycine absorption was maintained. When the dipeptides were perfused, free amino acids appeared in the perfusate presumably by "back diffusion" from the mucosal cells. In the case of glycyl-L-leucine considerably more glycine and leucine were found in the perfusate in patients with sprue than in the control subjects. There was no correlation between peptide absorption and the concentration of total glycly-glycine hydrolase and glycyl-L-leucine hydrolase, measured as combined brush border and cytosol enzymes. The concentrations of these enzymes were similar in both groups of subjects.


Permeability of the small intestine after intra-arterial injection of histamine-type mediators and irradiation. Permeability and selectivity of rabbit small intestine were estimated by a perfusion technique after intra-arterial injection of histamine-type mediators and intestinal irradiation. It was shown that the histamine-type mediators caused an increase in capillary permeability which produced an overall moderate increase in transmucosal permeability with a moderate loss of selectivity. Local intestinal irradiation caused a very marked increase in permeability and a profound loss of selectivity. It was felt that this was produced partly by an increase in capillary permeability but largely by damage to the epithelial basement membrane. It is concluded that the intestinal capillary endothelium is both rate-limiting and selective, though not to a major degree in either case. The epithelial basement membrane, however, appears to be both rate-limiting and markedly selective.


Influence of staphylococcal enterotoxin on water and electrolyte transport in the small intestine. The direct and indirect effects of staphylococcal enterotoxins A and C on the flux of water, sodium, and potassium have been studied in paired Thiry Vella fistulae in dogs. Administration of toxin resulted in a significant decrease in absorption, both in the loop to which the toxin had been administered and its pair. This decrease in absorption was associated with a decrease in movement out of the lumen, movement into the lumen remaining relatively unchanged. The mechanism of action of staphylococcal enterotoxins is discussed, and comparisons made with other enterotoxins.


Effect of gastrin on gastric mucosal cell proliferation in man. The effect of short-term infusion of a large dose of pentagastrin and a small dose of synthetic human gastrin I (SHG) on the rate of cell proliferation in gastric mucosa was studied in normal human subjects. Moreover, the kinetic parameters were compared with the serum gastrin concentrations in fasting patients. Endoscopic biopsies were labelled in vitro with 3H-thymidine and autoradiographs were prepared. The percentage of DNA-synthesising cells in the progenitor cell region was estimated. In healthy volunteers infusion of a large dose of pentagastrin (10 mug/kg per hour) was followed by a marked increase in the labelling index in fundic mucosa. The antral mucosa was not responsive to this effect. In the same subjects, infusion of a low dose of SHG (8 ng/kg per min) did not affect the rate of cell proliferation, either in fundic or in antral mucosa. In 46 patients with different gastric diseases no correlation between the serum gastrin concentrations and the labelling indices was found. The results suggest that human fundic mucosa is responsive to a trophic action of pentagastrin. If it exists, however, a physiological action of gastrin as a trophic hormone for human gastric mucosa must be considerably more complex than previously believed.


Gastric emptying in control subjects and patients with duodenal ulcer before and after vagotomy. The emptying of a solid meal labelled with Indium 113mDTPA from the stomach was studied with a gamma camera in 26 normal subjects, 27 patients with duodenal ulcer, on 41 occasions after truncal vagotomy and pyloroplasty and 38 times after highly selective vagotomy. Applying the method of principal component analysis to the results, differences were detected between control and duodenal ulcer subjects and two probable subgroups of duodenal ulcer were observed. Half emptying times did not reveal these patterns. After vagotomy, delayed emptying was general at one week. At one month, patients after highly selective vagotomy had a more normal result than those with truncal vagotomy and pyloroplasty (TV), but by six months no significant difference in overall emptying rate was found, although changes in the pattern of gastric emptying persisted in some patients after TV.


Gastric morphology and serum gastrin levels in pernicious anaemia. Mucosal biopsies from multiple sites in the stomachs of 21 patients with pernicious anaemia have been examined. The histological changes almost always involved the entire gastric mucosa, including that of the pyloric antrum. Metaplastic changes were almost universal and consisted of intestinal metaplasia in the body and antrum and pyloric metaplasia in the body. The severity of the pyloric metaplasia was such as to make the distinction between body and antrum on biopsy impossible. No relationship was found between serum gastrin activity and the histological appearances of the gastric antrum or body.


Tissue demonstration of carcinoembryonic antigen (CEA) in ulcerative colitis. An immunoperoxidase technique was used to demonstrate carcinoembryonic antigen (CEA) in sections of proctocolectomy specimens from nine cases of ulcerative colitis in some of which carcinoma and premalignant change had developed. Carcinoma and premalignant change stained positively for CEA in contrast with benign mucosa, whether or not inflammatory dysplasia was present.


Cell contacts and distribution of nerves in the smooth muscle of estrogen-dominated rabbit oviduct. The types of cell-to-cell contacts and the relationship between the nerve endings and the smooth muscle of the estrogen-treated rabbit oviduct have been investigated. The cell contacts most consistently found in the oviduct were simple appositions, with a 20-nm cell separation, which occasionally included a more dense region, and interdigitations of muscle cell processes with the same separation distances. Very rarely, wider intermediate contacts were present. Gap junctions (nexuses) were absent. It seems likely that simple appositions and interdigitations form the low resistance pathway for conduction of electrical activity. Nerves containing small dense-cored vesicles were present both within and near muscle bundles; they were rarely found close to smooth muscle cells.


Bulk flows through human fetal membranes. Bulk water flows across term human amnio-chorion are studied in vitro. The hydrodynamic permeability is found to vary with both hydrostatic and osmotic pressure. The coefficient characterizing flows generated by hydrostatic pressure is substantially larger than that characterizing osmotic flows. The measurements are utilised to predict in vivo bulk flows across the amnio-chorion. These lead to the prediction that at most a flux of 34-83 ml/day may occur across amnio-chorion directed outwards from the amniotic cavity, the principal contribution to this arising from the effects of hydrostatic pressure.


Permeability of chorion laeve to succinylcholine in vitro. The simultaneous diffusion of 14C-succinylcholine and p-amino hippurate across human placental tissue in vitro was measured. Column chromatographic purification of the radioactivity followed by paper chromatographic analysis showed little alteration of the succinylcholine during the course of these experiments. Similar chloroform-buffer partition coefficients for the two solutes were measured. Thus in these experiments, the nearly identical transfer rates of these two similar sized, lipid-insoluble compounds indicated that succinylcholine crosses human placental tissue in quantitites compatible with its molecular size and lipophobic nature, and that the diffusion rate is not significantly influenced by its increased molecular charge.


Suicides committed by minors.

Suicides committed by minors. The bodies of 76 minors, below 18 years of age, who died as a consequence of committing suicide during the years 1960 to 1974 were examined in the Institute of Forensic Medicine in Cracow. The youngest victim was a boy 8 1/2 years of age. The majority of cases (63) referred to minors aged 16-18. The deaths were due to: hanging (41 cases), poisoning (17 cases), leaping from a height (7 cases), and others (11 cases including one case of self shooting). Among the motives for suicide the first place is taken by personal troubles, mostly school failures, then bad health and family conflicts. Prior suicidal attempts were noted in 13 cases and in 10 others oral declarations of suicide were made. Motives for suicide essentially differ from those found in earlier studies from the years 1881-1939, where ill luck in love and undesired pregnancy were treated as one of the important factors leading to suicide.


The quantitative analysis of glass by emission spectrography: a six element survey. The use of emission spectrography for the analysis of small glass fragments (approximately 1 mg) is described. Levels of Al, Ba, Ca, Fe, Mg and Mn have been determined in approximately 200 samples, and with the exception of Ca their variation appears to be of value in the classification and/or discrimination of glass. The precision of the method has been studied and its accuracy determined by the analysis of standard glasses prepared in the laboratory.


Homicide in acute porphyria.

Homicide in acute porphyria. The subject was a young man known to suffer from the intermittent (Swedish) form of this disorder, who committed homicide in an acute attack of porphyria and who died from the disease 7 days later. The family history and clinical features of the acute attack are reported. The paper includes a brief review of the literature, with reference to the psychiatric features of acute porphyria.


[Epithelial barriers of the intestine. Significance and function in defense against infection]. The epithelial surface of the intestinal tract provides for an important barrier between the organism and its environment. However, it permits the passage into the tissues of limited amounts of macromolecules and/or particles, especially bacteria. These functions are age- and species-dependent, and they are closely related to nonspecific and specific immune reactions. Continuous and intimate contact between antigenic material from the gut lumen and immunocompetent cells takes place in gut-associated lymphoid tissues.


[Mushroom poisoning. New possibilities for treatment]. Poisonous species of fungi in Germany are very few. Dangerous is the ingestion of raw, spoiled or poisonous mushrooms. There exist no reliable tests to determine whether a mushroom is safe except by expert examination and identification of the mushroom. In clinical practice the classification of mushroom poisoning is possible in muscarine-syndrome, gastroenteritic syndrome and in two-phase-syndrome. 90-95% of lethal mushroom poisonings are due to ingestion of Amanita phalloides. In severe cases extensive hepatic necrosis occurs, characterized by profound abnormalities in liver function caused by hepatic coma. In deep coma mortality rates amount to 70% or more. A new therapeutic measure (coated charcoal hemoperfusion)-first applied in liver failure by Chang (1972) and Williams (1973)-has been performed in 3 patients with severe poisoning after ingestion of Amanita phalloides (each patient had eaten at least 7-10 fungi Amanita phalloides). Two of the patients survived.


Evaluation of column extraction: a new procedure for the analysis of drugs in body fluids. A method is described for the extraction of drugs from body fluids, whereby liquid-liquid extraction is replaced by liquid-solid elution. The aqueous sample is absorbed on a column filled with dry supporting material. By elution with organic solvents lipophilic substances are extracted from the water phase which remains on the column. The eluate containing the drugs is free of emulsions. For optimal extraction any pH value and a variety of solvents can be used. Column extraction of urine, serum and blood is easily performed and gives high recovery rates, which are superior to conventional extraction. Thin layer chromatography of drugs following conventional XAD-2 and column extraction, demonstrates identical qualitative results, but shows higher purity of the column extracts. The sensitivity of detection is enhanced.


[Antibiotic therapy for infectious enteritis in childhood]. A brief review of the actual knowledge on the infantile enteritis caused by infectious agents is given. The antibiotic therapy of bacterial enteritis is still acute, but the range of indications is limited. This kind of therapy aims at the curative effect, but not at the sanitation of the stools, for which no reliable method exists. Any kind of infantile enteritis needs dietetic treatment.


The increasing use of paraquat as a suicidal agent. Paraquat, the most important of the bipyridyl group of herbicides, has proved a most effective weedkiller and is now in world-wide use. When used as intended, the compound is quite safe, but misuse has led to a significant number of deaths. If taken orally in significant amounts a fatal outcome is likely and there is as yet no effective antidote. Deaths from paraquat poisoning have been proportionately higher in Ireland than elsewhere. The present paper analyses 26 fatal and 7 non-fatal poisonings occurring in Northern Ireland during the period 1967-1975. The history, clinical features, length of survival and pathological findings are discussed. Extensive toxicological analyses have been performed on samples taken during life, and on a wide range of body fluids and tissues obtained at autopsy. These data are presented and show the progressive but slow fall-off in paraquat recovery after ingestion, with detectable levels still present for up to 21 days. The increasing incidence of suicidal, as opposed to accidental, paraquat poisoning is stressed. The decline in accidental poisoning suggests that the measures taken to prevent accidental ingestion are proving successful. The swing from accident to suicide is reflected in the shorter survival times, differing autopsy findings and significantly higher tissue and body fluid levels encountered in suicidal poisonings.


Aspects of the hyoid-larynx complex in forensic pathology. Post-mortem radiological studies of the hyoid-larynx complex on excised specimens were undertaken. The post-mortem specimens were fixed to polysterene boards by ratio-translucent plastic pins. Radiological examinations revealed a fracture of the left greater cornu of the hyoid bone in a case of suicidal hanging; a fracture through the calcified right superior cornu of the thyroid cartilage in a case of blunt trauma to the left side of the head and neck; and a fracture artefact through the middle of the left greater cornu of the hyoid bone through compression of the structure by manipulation during the process of removal of the neck structures. In each instance the fracture sites were exposed and photographed. The use of a technique which permits a radiological examination of free dissected specimens of the hyoid-larynx complex has many advantages in the medicolegal investigations of injuries of the neck.


[Acupuncture, Theory and practice].

[Acupuncture, Theory and practice]. Trasditional Chinese medicine is based on inductive-synthetic reasoning with regard to all life processes, in contrast to the causal-analytic orientation in our Western medicine. This philosophical approach is based on a system of comparisons (equivalents), referred to as Yin and Yang. Vital functions are seen as "energizing" processes, whereby the acupuncture points and the system of meridians are seen as a means of regulation for this "energy". A disturbed balance in this energy results in illness. The therapy according to the acupuncture method is to acheive a balance in the disturbed flow of energy by means of acupuncture points. By utilizing biophysical methods of measurement, it is possible to prove that a change in this energy takes place. The complex active principle which results in the effectiveness of acupuncture includes neurophysiological, biochemical and biophysical functional processes.


[The thermal trigeminal impulse test. A method for more precise trigeminal nerve testing]. A new method is described, which determines the subjective sensitivity-level for warmth-impulses in the innervation-areas of trigeminus in the face. This method seems to be more sensitive than methods for judging the tactile sensitivity. The warmth-sensitivity shows no correlation to age and sex; the lowest level was found in the innervation area of the 2nd branch of trigeminus.


[Phlebography of the legs].

[Phlebography of the legs]. On the basis of more than 10,000 phlebographies we believe that the ascending phlebography with control by means of x-rays and accurate photographs, the so-called "phleboscopy", is the most appropriate of all techniques of phlebography for a routine ambulant examination of the veins. By means of phlebography we succeed in employing our therapeutical measures accurately, control of therapeutic results is possible. The phlebography informs about the morphological condition of the veinous system and the defluxion conditions. It serves for determining pathological conditions, such as the post-thrombotical syndrom in the case of acute deep thrombosis of the crural veins, and informs about the extent and defluxion conditions of the varicose veins as well as the sufficiency or insufficiency of the Vv. perforantes.


[Pharmacokinetics of angiographic contrast media]. The pharmaco-kinetics of angiographic contrast media in the extravascular space, which are largely unknown, were investigated experimentally in dogs. As part of a basic study, using radio-active contrast media, it was possible to determine the concentration and rate of elimination in practically all organs and tissues. Measurements were carried out first after prolonged infusion of the contrast under conditions of balanced flow, and secondly six hours after the end of the infusion. It was therefore possible to determine the inflow and loss of contrast medium in various organs or organ systems. The most commonly used angiographic contrast media in Germany were investigated. Their kinetic behaviour is largely identical, their pattern of distribution and elimination depended principally on the organ or tissue. In another study injections were carried out through angiographic catheters in a "physiological angiographic" manner. Measurements obtained show that distribution and excretion of the contrast medium are independent of the site of injection. The kinetics of the contrast within an organ do not differ, whether it is injected selectively or not. The presence of an entero-hepatic circulation of angiographic contrast media has been demonstrated, but quantitatively it is of little importance.


[Controversial caries prevention using fluorine]. Fluorine as an essential trace element is necessary for life. The artificial increase of the natural fluoride-content of drinking water up to a maximum of one milligram per litre has been proved a prophylactic step against dental caries. The available material is examined to find out how far side effects of this fluoride concentration as well as any higher fluoride doses can be brought in connection with special defects and patterns of diseases. A comprehensive review of scientific findings concerning physiological reactions caused by fluoride is given.


[Vascular malformations of the spinal cord. Diagnosis and therapy]. A review is given on the current diagnosis and treatment of spinal vascular malformations with special emphasis on the use of selective spinal angiography. Spinal vascular malformations are mostly encountered within the thoraco-lumbar segment of the spinal cord. Typical clinical symptoms are due to either progressive myelopathy or hemorrhage (subarachnoidal hemorrhage). The prognosis of untreated spinal angiomas is poor. Therefore, therapeutic measures are aiming to prevent bleeding of angiomas resulting in subarachnoidal hemorrhages or hematomyelia or to prevent spinal cord ischemia due to compression. Using selective spinal angiography, spinal angiomas can now be treated successfully by complete surgical extirpation or embolization procedures. The evaluation of radicular myelopathies and subarachnoidal hemorrhages of unknown origin has also considerably benefited from this technique. It is concluded that early diagnosis of spinal vascular malformations is of crucial importance for good therapeutical results.


[New methods in vascular surgery. Intraoperative transluminal catheter-recanalization using Dotter's technic]. The combination of vascular operative procedures and transluminal recanalization with a Dotter-catheter is recommended. According to own results this has been proven to be very successful, especially in old patients or in patients in a reduced physical state. The main advantage is a shorter duration of the surgical procedures and a reduction of the operative stress situation compared to other surgical methods. For the application of the Dotter-technique, however, it is necessary to observe the indications carefully.


[Nodular fascitis].

[Nodular fascitis]. Since 1971 four cases of Fasciitis nodularis were treated by the outpatient-department of the Surgical Clinic, Univ. of Erlangen. Alieno loco one patient's disease had been diagnosed as sarcoma, another patient had a lesion operated on which had been suggested being malignant by a pathologist. The danger in Fasciitis nodularis is, that it is easily considered a malignant process and therefore too radical a tumor therapy is performed. The differential diagnosis from clinical and histological point of view between Fasciitis nodularis and soft tissue tumors is presented.


[Recurrent skin tumors and their surgical management]. Recurrences of basal cell carcinomas and squamous cell carcinomas are possible in cases of radiation before surgical treatment. This inadequacy occurs in general, if the emphasis of the treatment was on the cosmetical point and therefore the necessary radical therapy had been neglected. Furthermore cicatrizing basal cell carcinomas are prone to recurrences, after only a macroscopical tumor extirpation had been carried out. In special cases of epidermal tumor recurrences our dermato-surgical proceedings are demonstrated. The repair of large skin defects, caused by surgical treatment, requires methods of plastic and reconstructive surgery. Should there be any doubt whether the therapy is radical enough, material for microscopical examination should be taken immediately.


[Echocardiography].

[Echocardiography]. Echocardiography makes possible the analysis of cardiac structures and their dynamics. The presence of valvular disease and its severity can be determined by evaluation of variations in the intensity of reflection and alterations in the motion of valvular structures. The echocardiographic representation of cardiac chambers permits the detection of congenital and acquired structural defects as well as an evaluation of ventricular function. Echocardiography provides a non-invasive means of diagnostic analysis throughout the spectrum of heart diseases and can replace a number of invasive diagnostic procedures.


[Leading neurological symptoms of internal diseases]. After description of the central-nervous signs due to hypoglycemia, hypoxia, hypo- and hypercalcemia there are discussed several internal diseases with prominent neurologic symptoms like endocrine disorders of thyroid, adrenal and pituitary gland, malignant diseases especially regarding the hematopoietic system, disorders of the joints and connective tissue and metabolic disorders as acute intermittent porphyria, uremic and hepatic coma. The principal differential diagnostic considerations in this relation are being described in order to avoid severe diagnostic errors.


[Acute hepatic coma. Experimental study on the predictive value of clinical-chemical findings for the prognosis of acute hepatic coma]. In order to determine the validity of clinical-chemical parameters for the prognosis of hepatic failure, 28 pigs were subjected to liver ischemia for 40--160 minutes duration. The following parameters were studied: GOT, GPT, gamma-GT, LAP, LDH, GlDH, AP and isoenzymes, total bilirubin, potassium, sodium and chloride. In a statistical comparison in the surviving animals, an unexplainable increase in GlDH activity was observed. In the other clinical-chemical parameters none was seen to be of use for the prognosis for either life or death in acute hepatic failure.


[Mycotoxins as a cause of disease in human beings]. Secondary metabolites, toxic to macro-organisms and micro-organisms, are produced by certain molds and some plant parasitic living fungi. A risk is given for man worldwide by ingestion or apparently also be other routes always undetected. In vivo-effects of the various mycotoxins are different, but mainly the liver is affected, expecially by the intake of smaller amounts of these poisons. Accordingly cirrhosis of the liver or primary liver carcinoma are expected in man as well as in animals and were already proved outside of Europe.


[Heart muscle after heart infarct. Function of surviving heart muscle following acute myocardial infarct]. In the initial phase of the infarction, there is a decrease of ventricular function due to loss of contractile activity. In addition, a negative effect of the paradoxical movement of the infarcted area on the hemodynamics of the ventricle is noted. The stiffening of the infarcted area in the early stage has a favorable influence on ventricular function, leading to a change in the elastic properties of the ventricle. The loss of ventricular compliance persists after the infarction, and its severity depends on the extent of myocardial destruction. In the non-compliant ventricle, the end-diastolic pressure rises without a proportionate increase in volume. Consequently, the ventricular function curve shows a shift downward and to the right, making it difficult to distinguish between the loss of contractile function or compliance in the heart in situ. Evaluation of the contractile properties of the surviving cardiac muscle in situ is, however, hardly possible due to the changed geometry and the additonal elastic elements functioning in series with the surviving muscle. To exclude these factors, a study of the contractile properties of the surviving cardiac muscle in the isolated state was carried out following experimental myocardial infarction in cats. By ligating several coronary branches, infarctions in the area of the left ventricle were caused; to avoid the ischaemic border zone of the infarction, right ventricular papillary muscles were studied. Haemodynamic investigations showed an increase in right ventricular end-diastolic pressure which persisted 6 weeks after infarction. As early as 48 hours but, more significantly 1 week after infarction, there was a decrease of actively developed force in the surviving cardiac muscle due to a lower rate of force development. The resting length tension curve of the surviving cardiac muscle after infarction showed no alterations; and 6 weeks following infarction, almost normal contractility parameters were observed. As a result of the infarction, a decrease in contractility in the surviving cardiac muscle is observed during the early stage, which regresses after complete recuperation.


[Value of results of animal experiments for the evaluation of drugs. 3. Animal trials and subjective probability]. Inasmuch as the findings in pharmacology and toxicology are based on animal trials these disciplines have to be considered as subjective sciences, since the experimentally obtained objective data become medically relevant only on the basis of subjective probabilities. The value of pharmacological and toxicological tests is dependent on the quality of the investigator. Data obtained in animals trials are of no relevance for human medicine unless the investigator substantiates his subjective probabilities and at the same time demonstrates how the hypotheses won in animal trials can be verified in man. Toxicological testing methods allowing the "preselection" of drugs or any other kind of deductions without verification in man do not exist. Animal studies which are not based on the principles of decision theory serve merely as an alibi and may lead to wrong conclusions. Besides, they interfere with the German Animal Protection Law. Methodological problems can neither be solved by normative regulations of an administrative authority nor by increasing experimental activity.


[The malignant struma. Pathological anatomy and functional criteria]. Description of the pathological anatomy of thyroid cancer with classification into carcinomas, sarcomas and special forms of tumors. Concerning the carcinomas of the thyroid gland, the malignant papilloma (papillary carcinoma) and the medullary amyloid- and calcitonin-producing carcinoma deserve special consideration because of their small malignancy and therefore favourable prognosis. Also the proliferating struma Langhans does not come up to "real" carcinomas (organoid structure of the tumor tissue) concerning the growing speed. All other types of carcinomas, as well as sarcomas, are fast growing malignant tumors, which also place metastases early. The metastasizing struma-adenoma is not a malignant tumor in the sense of the term. In addition, it is necessary to refer to the existing difficulties in marking off clearly structurally sarcomatous tumors of the thyroid gland from carcinomas. Besides, one must emphasize, that thyreostatic substances, also ionizing rays (i.e. radioiodine) can produce considerable tissue-changes with cell polymorphia and that a considerable increase in the number of large-cell eosinophilic adenomas (oncocytomas, Hürthle-cell adenomas) exists. The sclerosizing microcarcinoma (Graham's tumor) is not a carcinoma in the sense of the term.


[Retinal hemangiomas].

[Retinal hemangiomas]. In the present study the clinical picture, therapy and pathogenesis of 6 retinal diseases are individually described and discussed. These are: familial tortuosity of the small retinal arteries, arteriovenous haemangioma, cavernous haemangioma, Leber's multiple retinal aneurysms, Coats' disease and von Hippel's haemangiomatosis retinae. They can all be subsumed under the broad concept of haemangioma and represent hamartias and hamartomas of the retinal vascular system.


[Clinical experiences with vasoatherolip in early cerebral insufficiency]. Under clinical conditions and during 12 weeks Vasoatherolip (alufibrat and nicotinuric acid) were administered to a group of 30 patients suffering from definitive symptoms of early cerebral insufficiency. The daily dosage was 3 X 1 tablet. In about 66 per cent of the patients a significant improvement, especially for intellectual and affective capacity was achieved. This could be proved by a number of confirmed psychometrical tests (i.e. concentration-test, Benton-test, pegboard-test, Wechsler-test, etc.).


[Functional scintigraphy of the heat in congenital or acquired heart valve diseases]. Quantitative nuclear cardiography was applied to 400 patients with valvular heart disease proven by heart catheterisation. The study yielded the following results: 1. The parameters used were directly related to th4 cardiac index, the enddiastolic volume of the left ventricle and the pressures in the pulmonary vascular system. 2. The method proved to be highly sensitive in stating whether there was a hemodynamically effective valvular disease present or not. Differential diagnosis, however, was not possible. 3. The prolongation of the circulation times correlated with the hemodynamic severity of the disease. 4. The method could be used in evaluation of corrective surgery and for follow-up after operation.


[Side-effects of oral contraceptives under psychological-sociological aspects. Results of an empirical study on 345 women]. Do women without experience in taking oral contraceptives expect more side-effects than women, who use this contraceptive method, ever experienced? This question was examined on 345 women in pregnancy and childbed Psychological and sociological data, as personality factors, general well-being, school education, intelligence and age  were evaluated. The attitude towards the pill depended on the families opinion of the pill, fear of cancer, knowledge about the pill and experience of menstruation. Half of the women had never taken the pill. Those women expected more side-effects than women, who had taken the pill had experienced (p less than 0,05). Those women who had never taken the pill stated frequently, that their partner (p less than 0,001) and mother (p less than 0,001) rejected the pill. Three fourth of women without experiences in taking the pill doubted thepill to be safe. Two thirds of these women were anxious the pill might cause cancer. Four fifth of the questioned women thought a pregnancy would mean more stress than taking the pill, women without experience in taking the pill more frequently thought the pill to be more disturbing (p less than 0,01). Women who had never taken the pill, suffered more often from reduced well-being (p less than 0,05) and were also more often introverted (p less than 0,1). The more irregular and painful menstruations were, the more women accepted the pill (p less than 0,01). Women with experience in taking the pill had often higher intelligence (p less than 0,05) and a higher education level (p less than 0,01). This is important for the interpretation of the results. The results were statistically checked by the x2-method.


[Vena cava occlusion syndrome. Cardiovascular parameters and uterine blood supply]. In late pregnancy about 10% of the patients suffer from dizziness and a shock symptomatic if placed in a supine position. These symptoms are reversible if the patient turns to the lateral position. In the present paper experiments in human and sheep are reviewed. The cause for this disease is the occlusion of the inferior vena cava by the gravid uterus. The venous backflow to the maternal heart is reduced and the cardiac output decreased by about 1 1/min. The total peripheral resistance (TPR) is increased (Lees et al. 1967b). The increase in TPR is due to the compression of the vena cava by the uterus and not related to an increased arterial tone during the first time course. The fall in mean arterial blood pressure is of varying degree and paralleled by an increase of the blood pressure in the vena cava below the compression and the uterine vein. The fall of the mean arterial blood pressure war related to the decrease of the perfusion pressure. The fall in arterial blood pressure and most important the rise of the uterine vein blood pressure led to a decrease of the perfusion pressure across the uterus. The uterine blood flow fell proportional to the drop of perfusion pressure. The uterine vasculare resistance remained unchanged. The fall of uterine blood flow was associated with a fall of fetal heart rate.


[Indications for vital and preventive cesarean section]. The indications for Caesarean section have not only increased but also changed. A spectrum of indications is described which comprises emergency and preventive indications. The postpartal state of the newborn after Caesarean section (200 cases) is described regarding indication, 148 additional cases due to the change of indication. The lowest Apgar-scores were found in newborns after sectiones for emergency fetal indications. ithe increase of the Caesarean section rate since 1971 was due to preventive fetal indications, which reached in the last 2 years more than 50%. It was found that the ""Caesarean section infant'' is not endangered, but the infant delivered by Caesarean section for reasons of emergency indications of fetal or maternal nature. Control examinations during pregnancy should help to recognize the risk-pregnancy and to decide on necessary ambulant treatment or hospitalisation.


[Changes in the electrolyte and acid-base equilibrium during the first days of life]. The concentrations of potassium, sodium and magnesium in plasma, red corpuscels and acid-base status were measured during the first five days of life. Significant differences were observed during this period of  life, these values also differ markedly from those of adults. The causes of the particular conditions of the neonates are complex and not all known at present.


[Impulse cytophotometry in neoplasm prevention. The behavior of normal vaginal smears in the impulse cytophotometric histogram]. Evaluation of histograms of normal cervical and vaginal smears, produced by ""rapid flow through'' cytophotometry. Normal cytological cervical and vaginal smears were examined for their appearance in histograms in order to find criteria for the classification of ""normal non-pathological'' cytological slides. Simultaneously, the reliability of the standardized method for preparation of vaginal and cervical smears was checked. The diagrams and data produced by the histograph were also coded on line and analyzed by a computer; thus obtaining an objective mathematical analysis and avoiding errors due to subjective visual analysis of the histograms. The objective interpretation of histograms of normal vaginal smears is an important step to the realisation of automatic pre-screening.


[A reducing diet with a high proportion of bread]. 10 female and 10 male moderately obese persons, pursuing their usual activities, received a reduction diet for 4 weeks, in which 46% of the calories were supplied by rye bread. In percent of calories the diet consisted of 60% carbohydrates, 20% fat and 20% protein. The total intake of calories corresponded to 60% of the caloric requirement. Weight losses ranged from 1.8 to 10.7 kg; the mean was 6.0 kg. Serum cholesterol values tended to decrease by 15% on the average, triglyceride values decreased by 38%. All subjects declared to be satiated during the entire 4 week period. No significant differences between the influence of crumb and crust on weight reduction could be observed.


[The pathogenesis of multiple sclerosis. Cytotoxic antibodies against myelin sheath tissue in multiple sclerosis]. Cytotoxic antibodies to myelin can be demonstrated by the method of 51Cr-release from chick erythrocytes coated with myelin basic protein. The cytotoxic antibody is inactivated by heating to 56 degrees C and needs complement in order to exert its action. The antibody was determined as IgM and IgG. It has relative specifity and shows cross-reaction with other basic proteins. The cytotoxic antibody was found in only 8% of healthy persons. Patients with multiple sclerosis were positive in 87% of the cases and in acute cases in 94%. In other neurological diseases cytotoxic antibody was present in 64%. The occurrence of cytotoxic antibody to myelin protein is not specific for a particular neurological disorder, especially not for multiple sclerosis. Cytotoxic antibodies arise as a secondary phenomenon, they are not the cause of the disease involved. They appear to be suitable, however, to determine, in association with cellular immunological reactions against myelin which may be regarded as the "primary" immunological processes, the demyelination process in the multiple sclerosis focus.


[Stimulation of the bodies defense against cervix carcinoma. Clinical-experimental study]. The method of choice for stimulation is extracorporeal radiotherapy of the blood, which has undergone stepwise clinical experimental development, is recommended. Implementation of this method induces a marked increase in the biosynthesis of certain serum proteins, especially the IgM and IgG fractions of the gammaglobulins and there is a definite tendency to normalization of certain serum enzymes in patients with cervical carcinoma. The dose dependence observed in the present study and the good clinical tolerance shown to this radiotherapeutic procedure are emphasized. The investigation is concluded with a cautions appraisal of the possible mode of action of extracorporeal X ray-irradiation of the blood at a dosage of 5000 R/O.


[Infant nutrition in West Africa].

[Infant nutrition in West Africa]. The breastfeeding-customs of Westafrican tribes are described. Details are given about the duration of the suckling-period, about the nourishment of the baby after breastfeeding has been reduced and about the application of indigenous lactogenic substances. The relations between mother and child as well as the relations between wife and husband during the suckling-period are illustrated; the dangers of a precocious weaning from breastfeeding and the dangers due to the application of wrongly prepared bottle-milk are discussed.


[Juvenile psychogenic hearing disorders]. Psychogenic hearing problems exist even in childhood. They must be differentiated from the stimulated or aggravated hearing losses. A characteristic is the discrepancy between the understanding during conversation and the bad results of the hearing tests. The psychical case history of the patient shows his conflict-situation and personal problems. If the psychogenic hearing problems do not improve on their own or by means of oto-rhinolaryngical placebo-therapy, psycho-therapy will be needed. Taking the example of 2 children, where the suspected primary diagnosis was sudden deafness, the problems of diagnosis was shown.


[Endoscopy, a hobby for specialists--or more?]. In the years between 1958 and 1970, diagnostic endoscopy made decisive advances. In this period, the ground was prepared for operative endoscopy. This applies not only to the technical, but also to the psychological aspects. The fact that formerly hidden structures could now be directly inspected and ""grasped'', spurned the endoscopist to intensive activity. Polypectomy, papillotomy with the removal of gallstones and, increasingly, photocoagulation for the arrest of bleeding, have made in many cases classical surgical operations superfluous. In close cooperation and rapport with the surgeons, the indications for, but also the limitations of, the new procedure are being established. In addition to the more practical aspects, modern endoscopy has also created a bridge to better understanding of biochemical processes in the gastrointestinal tract. The possibility of being able to investigate the effects of newly discovered, analysed and synthesized gastrointestinal hormones has been considerably improved. Endoscopy, formerly considered, more or less, a hobby for a few specialists, has become a sort of intermediary system which is capable of providing excellent diagnostic information, of making possible elegant therapeutic measures and of producing new biochemical information. In this creative function, it is surpassed by virtually no other method. A pre-condition for this development was, however, that the endoscopist was not content to remain merely an observer of interesting views, but was, rather, an active physician, to whom the advantages to the patient of early detection of disease and suitable therapeutic measures were equally important as the useful information obtained on biochemical relationships.


[The use of vaginal tampons in hospital and practice]. Industrially manufactured cotton wool tampons have been used for 5 years on approx. 5,000 women. The tampons were used in cases of inflammatory diseases of the vagina and of the cervix as well as postoperatively after abdominal and vaginal operations in order to apply medicaments. The absorbing effect of the tampons immediately stops the disagreeable secretion. The insertion of the tampons is simple and can be performed by the women themselves. Use of the pre-fabricated tampons is more economical than that of those tampons developed by our personnel. The advantages of the tampons during menstruation as well as during sports activities while menstruating are discussed. No side effects were observed during tampon use provided the tampons were inserted correctly.


[Histamine-H2-receptor antagonists. Physiological and clinical aspects]. Histamine-H2-receptor antagonists (Burimamide, Metiamide, Cimetidine) may inhibit histamine-stimulated gastric secretion in various species including man; in constrast, conventional antihistaminics (H1-antagonists) do not do so. Gastric secretion as stimulated by pentagastrin, insulin, 2-deoxy-glucose or an intragastrically instilled meal is also decreased by H2-antagonists, and a final common mediator role for histamine in the gastric secretory is discussed. H2-antagonists do also inhibit pancreatic enzyme secretion, but do not affect at all bicarbonate secretion. Recent clinical trials have shown Metiamide to be superior to placebo in therapy of duodenal ulcer.


[Preventive medicine aspects in the sex education of young girls]. Girls in their teens have many questions and uncertainities regarding their physical maturation. In many cases personal hygiene is insufficient, resulting from lack of information and education in the family. The onset of menarche introduces a new dimension of life to cope with. Competent advice is essential in these habit-forming years to correct misconceptions and lead to proper health care.


[Diagnosis of hydrocephalus. Changes in visual evoked potentials in children with progressive hydrocephalus internus]. Visual evoked potentials (VEP) of 12 children with progressive hydrocephalus internus were studied. Depending on the severity of hydrocephalus internus VEP show remarkable changes. First of deformation of VEP occurs, than a slowing of latencies and finally an extreme increase of latencies combined with a further deformation of VEP. The whole duration of the VEP shows a marked prolongation.


[Folk medicine, experience therapy, a component of modern therapeutics?]. Empirical medicine has three main supporting pillars: physical treatment, dietetics and phytotherapy. In this area of medicine, a number of therapeutical methods have been evolved which stand up to investigations employing scientific criteria, and which, in consequence, have become officially recognized by medical science. Examples are: diet rich in bulkage, digitalis, products of Papaver somniferum (Poppy) and salicylates. The acceptance of phytotherapeutic agents into the drug armamentarium of scientific medicine presupposes the availability of test methods suitable to demonstrate their effectiveness. Quite a number of remedies that have always been firmly anchored in empirical medicine, but which was applied regularly only by the nature healer, have suddenly, in the light of new test methods, been shown to be effective medicines; thus, for example, onions and garlic are good for thrombotic processes and hyperglycaemia, carminatives for sphincter spasms in the gastrointestinal tract, and alcohol is an appetite-stimulating stomachic. This fact, the limited applicability of the information obtained from animal experiments, and the further fact that even test results obtained in human subjects cannot be applied on a world-wide basis, exhort us to take care not to subscribe to an all-too apodictic classification of therapeutic measures into effective and noneffective. A further point for consideration is that the administration even of what is only a supposed remedy, can trigger or promote healing simply on the strength of the action of the physician. Scientific thinking is an indispensible precondition of the physician's activity--to consider it as the beginning and end of all things medical, however, is simply to demonstrate a narrowness of outlook.


[Emergency situations in drug addicts. Classification, diagnostic and therapeutic measures]. In drug addicts emergency situations can occur which differ only slightly in symptoms but require different therapeutic measures, depending on type of the drug and symptomatology. Diagnostic and therapeutical difficulties in emergency situations, especially the not unfrequent late complications and the considerable danger of suicidal actions require in general the immediate hospitalization. Intensive care and surveillance are necessary. The adequate therapy of ventilatory and circulatory functions is of great importance and should be started by the first consulted physician before transport to the hospital.


[Treatment of primary chronic polyarthritis in special cases]. Empirical medicine has three main supporting pillars: physical treatment, dietetics and phytotherapy. In this area of medicine, a number of therapeutical methods have been evolved which stand up to investigations employing scientific criteria, and which, in consequence, have become officially recognized by medical science. Examples are: diet rich in bulkage, digitalis, products of Papaver somniferum (Poppy) and salicylates. The acceptance of phytotherapeutic agents into the drug armamentarium of scientific medicine presupposes the availability of test methods suitable to demonstrate their effectiveness. Quite a number of remedies that have always been firmly anchored in empirical medicine, but which was applied regularly only by the nature healer, have suddenly, in the light of new test methods, been shown to be effective medicines; thus, for example, onions and garlic are good for thrombotic processes and hyperglycaemia, carminatives for sphincter spasms in the gastrointestinal tract, and alcohol is an appetite-stimulating stomachic. This fact, the limited applicability of the information obtained from animal experiments, and the further fact that even test results obtained in human subjects cannot be applied on a world-wide basis, exhort us to take care not to subscribe to an all-too apodictic classification of therapeutic measures into effective and noneffective. A further point for consideration is that the administration even of what is only a supposed remedy, can trigger or promote healing simply on the strength of the action of the physician. Scientific thinking is an indispensible precondition of the physician's activity--to consider it as the beginning and end of all things medical, however, is simply to demonstrate a narrowness of outlook.


[Mineralocorticoid syndromes and hypertension]. Mineralocorticoids are out of the causes of secondary hypertension. Excess production of mineralocorticoids induces sodium and fluid retention, loss of potassium and metabolic alcalosis. The diagnosis of mineralocorticoid syndromes depends on the interpretation of the functional status of the renin-mineralocorticoid-system, which is in part responsible for the maintenance of normal blood pressure. The classical representative of this group is the syndrome of primary aldosteronism. Causes of mineralocorticoid syndromes associated with hypertension are: 1. autonomous production of mineralo-corticoids by an adrenal adenoma or by idiopathic bilateral adrenal hyperplasia; 2. deficiency of adrenal 17-alpha-hydroxylase or of 11-beta-hydroxylase; 3. secondary aldosteronism associated with primary reninism, or renal arterial stenosis; and 4. pseudo aldosteronism due to excessive ingestion of licorice. Malign or essential hypertension may also often be followed by secondary aldosteronism.


[Cerebral embolism as a complication. Incidence and pathogenesis after heart infarct]. By means of clinical studies the frequency of cerebral embolic incidents after myocardial infarction was clarified. It is referred to the importance of some risk factors. The value of long time anticoagulant therapy is discussed.


[Diabetes mellitus and microcirculation. Significance of diabetic angiopathy for the prognosis and course of diabetes mellitus, possibilities and bases of angiologic therapy]. The importance of diabetic angiopathy for prognosis and course of diabetes mellitus, possibilities and basis of angiological therapy Complications originating from the vascular system determine life expectancy of the diabetic patient. He is particularly endangered by apoplexy, heart attack, arteriosclerosis of the lower extremities, retino- and nephropathy. Microangiopathy is a specific diabetic problem, the development of which shows a clear dependency on the quality of metabolism. Conventional therapy of circulatory problems today is less concerned with the vascular system than with the qualities of blood viscosity. In this context, viscosity is of main concern. Particularly in microcirculation viscosity is dependent on blood factors such as: haematocrit, plasmaviscosity, erythrocytes and thrombocytes. Their changed behaviour results, in the case of diabetes mellitus, in an increase in viscosity partly dependent on metabolism. A promising concept of treatment is available by pharmaceutically influencing the alteration of erythrocytes.


[Suicide and the weather. Risk of suicide in mental disorders and possibilities for prevention]. The risk of suicid in psychic disorders and possibilities of suicid prophylaxis The mysterious connection between weather and suicidal acts has been of particular interest at all times. In the past years extensive studies were carried out. But often the results were differing from each other. Nowadays, every person, committing suicid is regarded as psychically disturbed. Therefore, it may be better to analyse the diagnoses retrospectively and to determine which type of psychiatric illness is reacting significantly to which meteorological event. The results of this study using the "coincidence method" (n = 17 268) make it possible to give exact clues, which meteorological event may be dangerous to which kind of psychiatric illness. The time before a change of weather is of importance. The daily medical-meteorological telephone-service in the Federal Republic of Germany (bioprog) is therefore a biometeorological contribution to the prophylaxis of suicides.


[New method of thrombocyte counting. Technic of electronic counting of low thrombocyte concentrations in peripheral blood]. Starting from recent studies of Balleisen (1972) and Schmidt et al. (1973) about automated counting of platelets an automated method has been developed for accurate platelet counting at very low platelet concentration of peripheral blood. The method can be summarized as follows: 0,1 ml anticoagulated venous blood (Na-EDTA or polystyrol tubes containing EDTA powder) or capillary blood from finger tips was diluted with 20 ml of a mixture of Isoton-Periston-(Bayer-)Na2-EDTA (22:2:1 vol.) in polystyrol tubes. After 5 min centrifugation at 85 g, using an angle head and decantation into a polystyrol tube, second centrifugation. Decantation in a Coulter glass and counting at aperture 8, attenuation 0.500 and theshold 6 respectively 70 using at 70 mikron capillary. Counts at threshold 70 (erythrocyte counts) were subtracted from counts at threshold 6 (platelets and erythrocytes); to calculate platelet counts/mm3 multiplication by factor 2 at undiluted venous or capillary blood. The mean variation coefficient of our method being 4,1%, counting of platelets is possible with the accuracy of other automated methods at normal platelet concentration. At very low platelet counts our method seems to be the most accurate laboratory method for platelet counting.


[Artificial anus. Advantages and disadvantages of ileo- and colostomy]. The majority of patients with ileostomy adapt to their new situation and are able to live a nearly normal professional and social life. This does not mean that there is not a need for improvement in the ileostomy construction. It merely proves the great adaptive mechanism in man. In spite of the improvement in surgical techniques in the construction of the ileostomy and the development of modern ileostomy appliances, a proportion of the patients still experiences serious problems. In order to improve the situation for patients with ileostomy a new type of ileostomy has been developed. From the terminal ileum an intraabdominal, intestinal reservoir is constructed and the outlet from the reservoir is provided with a "nipple valve" preventing leakage of gas and faeces through the outlet. The continent ileostomy has now been under clinical trial for more than seven years. The success-rate has increased along with improvements in technique and introduction of methodological modifications. More than 90% of 164 patients provided with this type of ileostomy had at follow-up satisfactory functional results of their ileostomy. That means that they had no need for carrying external ileostomy appliances. A method for constructing a continent colostomy has been tested in dogs. The sigmoid colon was divided and the distal end closed. At the proximal end a "nipple valve" was constructed by intussuscepting a part of the intestine into its lumen. All dogs were continent from the time of operation until they were sacrificed one to eight weeks later. The method is now under elaboration for clinical trial.


[Manifestations of systemic diseases in the gastrointestinal tract]. Under the aspect of systemic diseases and their manifestation in the gut the following conclusions can be drawn: 1. The skin is the mirror of the intestinal tract; not only in primary gastroenterological disorders one should look for dermatological complications, but should also think in chronic skin lesions of concomitant intestinal alterations. 2. In all patients with collagen diseases a gastrointestinal involvement is very common. 3. In all endocrine disorders except in hypothyroidism diarrhea is a very common finding. 4. Infiltrations of gastrointestinal tract can be demonstrated in many cases by gastric, small bowel or rectal biopsy. 5. In all forms of dysgammaglobulinemia giardiasis is very common. 6. In right heart failure protein-losing enteropathy should be considered, in left ventricular insufficiency bowel ischemia.


[Heart pacemaker with lithium batteries. 2 years' clinical experience]. 102 lithium-powered cardiac pacemakers manufactured by Cardiac Pacemakers Inc. (CPI 301 UD, 101 UA and 501 UD) were implanted in 94 patients. During the observation time (25 months) the following complications were registered: 2 pulse generator failures, 4 failures of the demand-function, anodic muscle-twitching in 2 patients, 2 erosions of the pacemaker-pocket and 1 hematoma of the pocket. 5 pulse generators were exchanged without malfunction of the pacemaker. In 4 patients reinterventions on the electrode had, to be performed. 4 deaths occurred, none of them related to malfunction of the pacemaker. 2 lithium-powered pacemakers were explanted in other hospitals, for reasons not known to us and 1 patient left the German Federal Republic. 83 patients are under control with well working lithium-powered pacemakers.


[Glaucoma prevention].

[Glaucoma prevention]. All glaucomatous eye damages are caused by a too high intra-ocular pressure. This damage of the eye nerve leads in chronical cases from a slowly increasing loss of the visual field, which is usually not noticed by the patient, to total blindness. Prophylactic examinations should be introduced to all persons over 40 years old. The examination should consist of the measurement of the intra-ocular pressure and should be carried out within a period of 3-5 years.


[Contact lenses for children. Indications and results]. If it is necessary to prescribe contact lenses for children, this correction should be made as soon as possible. As a consequence of the development of soft (hydrophile) lenses, the above mentioned group of patients has increased considerably. In any case, a monolateral aphakia as well as a manifest anisometropia should be corrected by a contact lense to avoid amblyopia, heterotropia and loss of stereoscopic vision. Usually soft lenses are well tolerated, so that patients suffering from aphakia as well as hyperopia should always use this type of lense. Nevertheless, the hard lense still has its indication in treating myopia and high astigmatism.


[Value of the results of animal experiments for the evaluation of drugs. 2. Methodology and prediction of effects]. The efficiency of animal trials is critically examined against the background of the new EC drug regulations. The present contributions deal with the problem of predictability of qualitative events. It is established that the so-called "pharmacological properties" of substances do not exist. Further it must be taken into account that observations made on test animals are reductionistic in relation to man. The study also shows that it is difficult to predict events with reasonable certainty even within one particular animal species. The problem of extrapolation is being viewed under three different aspects: when there is no previous experience at all, when there is relevant previous experience, and when there are animal models available. In the first case, it is impossible to make any prediction at all. In the second case, only subjective suppositions are possible. As to the third case, it is an open question at the moment whether animal models do exist at all. According to the present state of science it is not possible to make objective predictions for man on the basis of animal trials. In regard to animal trials, the EC regulations stand in contrast to science and the methodology of statistics. The subjective nature of prediction will be discussed in the following contributions.


[Malignant systemic diseases of the digestive tract]. In about 5-6% of all patients with malignant myeloproliferative disorders the gastrointestinal tract is involved with macroscopic lesions. The most common sites of digestive manifestations are stomach, small bowel, pancreas and colon. Multiple irregular ulcers, doughy infiltration of the bowel wall, multiple nodules and diffuse polyposis of the colon are classic patterns of secondary lymphoma of the gut. Prognosis is considerably impaired by gastroenterological symptoms.


[Comparative studies of the psychosomatic aspects of liver diseases]. Connections between disturbed functions of liver and mental diseases at all times have been generally supposed as existent and have been discussed in the literature; they should be clarified by means of questionnaire-tests: MPI-test and MMQ-test of Eysenck combined with neurotizism-depression-questionnaire of Hoffmann-La Roche allowed to comprehend the dimensions of personality "neurotizism" and "depressivity". Concerning "neurotizism" statistically significant differences could be found between liver-patients and healthy persons in a tendency to a significant increase among liver-patients, but not between liver-patients with other diseases. The tendency to "depressivity" of healthy persons could be statistically evaluated as being much greater than that of liver-patients; there were no differences between liver-patients and patients with other diseases. That is why liver-patients do not differ psychically from patients suffering from other diseases; they share their reaction to the occurrence of disease - in various degrees until a neurotic lack of active realization of the fact of illness. Liver-diseases apparently are not triggered or caused by special pre-morbid alterations.


[Desire for children and the practice of family planning]. Of 1647 women in confinement (mean age 26years) and 185 students nurses (mean age 18 years), the majority wanted two children. 8% of the women in confinement and 2% of the student nurses had received no previous family planning information, whereas 38% of the women in confinement and 81% of the student nurses had practiced contraceptive methods with a Pearl-index of 3 or less (oral contraceptives, basal-temperature-method). 31% of the women in confinement had already had unplanned pregnancies (mean: 1.4 pregnancy per woman). The last pregnancy was not planned in 27% and in these 4 out of 5 pregnancies were caused by incorrect application of the contraceptive method. Faulty practices and unsatisfactory results, in spite of the availability of secure contraceptive methods, emphasize the necessity of intensifying family planning. Because programmes including personal counsel have yielded better results, these should be favoured and include a clinical post partum programme. The latter was considered necessary by 95% of the women attending such a programme in our hospital.