Tumors of Sprague-Dawley rats induced by long-term feeding of phenacetin.

Carcinogenicity of phenacetin was tested using Sprague-Dawley rats. Two groups of animals containing 50 males and 50 females per group were fed respectively with 2.5% and 1.25% phenacetin diet for 18 months and fed thereafter with basal diet for 6 months. Control animals containing 65 males and 65 females were fed with basal diet for 24 months. Animals surviving more than 24 months were regarded as effective animals and killed. Rats that died of tumor development within 24 months were also regarded effective animals. Every organ from the killed and dead animals was fixed in 10% formaldehyde solution and examined histopathologically. Effective number of rats was 27 males and 27 females in 2.5% phenacetin feeding group, and 22 males and 25 females in 1.25% phenacetin feeding group. In control group, 19 males and 25 females were effective. Neoplasms including spontaneous tumors were detected in 26 out of 27 males (96.3%) and 21 out of 27 females (77.8%) of 2.5% phenacetin feeding group, and in 20 out of 22 males (90.9%) and 19 out of 25 females (76.0%) of 1.25% phenacetin feeding group. In control group, 1 out of 19 males (5.3%) and 6 out of 25 females (24.0%) showed spontaneous tumor development. Histopathologically, carcinomas of the nasal cavity, such as adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma, and the urinary passage, as renal cell carcinoma of the kidney pelvis, and transitional cell carcinoma of the urinary bladder, were most conspicuous, suggesting the target organs of phenacetin carcinogenesis. Males showed higher tumor incidence compared to females. The higher the concentration of phenacetin given, higher incidence of tumors was observed.


Effect of Nocardia rubra cell-wall skeleton on the induction of lung cancer in ACI/N rats.

Administration of oil-attached Nocardia rubra cell-wall skeleton (N. rubra-CWS) was evaluated for the effect of the induction of lung cancers in ACI/N rats. Lung cancers were induced by 15 weekly intratracheal instillations of 3 mg benzo[a]-pyrene with 3 mg ferric oxide. After the 10th instillation of the carcinogen, rats received seven subcutaneous injections of 100 microgram of N. rubra-CWS at 2-week intervals. In the observation period of 56 weeks, the cumulative incidence of lung cancer was 71.4% in the control group and 48.0% in the N. rubra-CWS treated group. The latent period of tumor induction was prolonged in the group treated with N. rubra-CWS.


Effect of trichloropropene oxide and benzoflavone on polycyclic hydrocarbon carcinogenesis in C3H/He and DBA/2 mice.

Effect of 1,1,1-trichloropropene 2,3-oxide and 7,8-benzoflavone on benzo[a]-pyrene and 3-methylcholanthrene carcinogenesis in the subcutaneous tissues of C3H/He and DBA/2 mice was examined. By a single application of the carcinogen, the incidence of fibrosarcoma was higher and the latency of tumorigenesis was shorter in C3H/He mice than in DBA/2 mice. Treatment with 1,1,1-trichloropropene 2,3-oxide increased the incidence of fibrosarcoma in DBA/2 mice, but decreased the rate in C3H/He mice, when benzo[a]pyrene was used as a carcinogen. On the other hand, in 3-methylcholanthrene carcinogenesis, no effect of the oxide on the tumor incidence was observed. By the simultaneous application of 7,8-benzoflavone with benzo[a]pyrene, the tumor incidence increased, but not so significantly in DBA/2 mice, compared to that treated with benzo[a]pyrene alone, and no appreciable effect was observed in C3H/He mice treated with benzo[a]pyrene, and in both strains of mice with 3-methylcholanthrene. The relationship between the activity of arylhydrocarbon hydroxylase and the change in polycyclic hydrocarbon carcinogenesis is briefly discussed.


Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma.

Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I AND II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size.


Suppressive effect of prednisolone on cytotoxicity of lymphocytes from normal persons against T24 cells.

While lymphocytes from normal persons exhibited cytotoxicity against T24 cells, prednisolone at a concentration as low as 10(-7) M significantly inhibited the cytotoxic reactions and almost complete inhibition was observed at the concentration of 10(-4) M. The inhibitory effect was shown to be progressively decreased when prednisolone was added during the cytotoxicity assay of normal human lymphocytes. These findings suggest that the cytotoxicity of lymphocytes from normal persons can be suppressed by immunosuppressive effect of prednisolone and that the early phase in the cytotoxic reaction is considerably sensitive to prednisolone.


Gastric emptying in normal subjects and patients with peptic ulcer: a study using the acetaminophen method.

Gastric emptying in patients with peptic ulcer and normal subjects was studied using the acetaminophen method. The subjects consisted of 15 normal subjects, 52 gastric ulcer patients and 65 duodenal ulcer patients, who were studied in active stage of the ulcer. As an indicator of gastric emptying, the plasma acetaminophen concentration was measured by dye method (diphenylhydrazyl), as mcg/ml, at 45 minutes after ingestion of a high calory pasty test meal (200 ml) with 1.5 gr of acetaminophen. In normal subjects, the plasma acetaminophen concentration was 9.4 +/- 3.6 mcg/ml. In gastric ulcer patients, the concentration was 7.4 +/- 3.2 mcg/ml, which showed significantly delayed gastric emptying (P less than 0.05). In duodenal ulcer patients, the concentration was 11.6+/-3.3 mcg/ml, which suggested significantly rapid gastric emptying (P less than 0.05). In consideration of gastric secretion, gastric ulcer cases with lower acid secretion have more delayed gastric emptying. In duodenal ulcer cases with hypersecretion, gastric emptying is more rapid than normo-and/or hyposecretory cases (P less than 0.005). The delayed gastric emptying may play a role in etiology of gastric ulcer. On the other hand, the rapid gastric emptying with gastric acid hypersecretion may be important in the pathogenesis of duodenal ulcer.


A newly improved sliding tube for colonoscopy for keeping the sigmoid colon in a straight condition.

Although a sliding tube made of plastics is very effective to keep the sigmoid colon in a straight position, there is some difficulty in handling the colonoscope, being restricted by the length of the scope. For the purpose of covering the demerits of the conventional sliding tube, a new slit sliding tube which is made up of three parts was devised by us. After straightening the sigmoidal loop, the three parts of the apparatus are joined together. Then the slit sliding tube is inserted into the descending colon with safety and ease. By using the slit sliding tube, handling of the colonoscope is scarcely restricted and becomes easy. Moreover, the slit sliding tube can be used even for the shorter scopes, by which the distal parts of the colon can be more easily examined in comparison with conventional techniques.


Endoscopic diagnosis of intestinal metaplasia in asymptomatic (control) volunteers.

The F-P border and strain phenomenon of the gastric mucosa were investigated by the application of methylene blue dye spraying method in endoscopy to 105 asymptomatic control volunteers and the following results were obtained; 1. The pyloric metaplasia is observed in the fundic gland area from the twenties in age and becomes increasing in its number and move widely spreading from the lesser curvature to the anterior and/or posterior wall of the corpus with advancing age. 2. The intestinal metaplasia arises from the thirties in age. 3. The intestinal metaplasia is observed either in the pyloric gland area of following the pyloric metaplasis in the fundic gland area. 4. Histologically, the strain phenomenon of the gastric mucosa is closely related to the intestinal metaplasia. Then, methylene blue dye spraying method is reevaluated to be useful for a precise endoscopic diagnosis of intestinal metaplasia.


Studies on drug-induced allergic intrahepatic cholestasis--hepatic cholestasis induced in dogs by lymphocyte culture supernatant.

When peripheral lymphocytes from patients with drug-induced allergic intrahepatic cholestasis were stimulated with a specific drug in vitro in the presence of a liver microsome fraction or soluble liver specific antigen fraction, lympholine production was seen in many cases. By the injection of culture supernatant of stimulated lymphocytes into the mesentery vein of dogs, cholestasis was induced in the liver, chiefly in the central zones of lobules. However, no cholestasis could be observed in dogs administered the supernatants of lymphocyte cultures prepared from normal individuals in the presence of drugs. Moreover, only slight swelling of the hepatocytes was observed in the liver when normal lymphocytes were stimulated with PHA-P and culture supernatant was injected into the mesentery vein of dogs. These results suggest that sensitized lymphocytes may produce a factor (or factors) by stimulation with a specific drug-carrier and this factor (or factors) causes cholestasis in the liver.


Lipid peroxidation and lysosomal enzymes in D-galactosamine hepatitis and its protection by vitamin E.

Role of lipid peroxidation on lysosomal instability in liver tissue was investiaged in an experimental model of D-galactosamine hepatitis in rats fed on vitamin E (V.E) deficient diet. Administration of D-galactisamine to V.E deficient rats resulted in a sudden increase of serum glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT), lipid peroxide value, as well as beta-glucuronidase and acid phosphatase activity examined as markers of lysosomal enzymes, when compared with control rats fed on V.E supplemented diet. Lipid peroxide in the liver tissue also showed significant increase in V.E deficient rats. In contrast, beta-glucuronidase and acid phosphatase in the liver tissue were found to decrease in V.E deficient rats by the administration of D-galactosamine, indicating that the enzymes in the lysosome were entirely released outside the liver cells as a result of cell destruction. It is concluded that the increase of lipid peroxide causes the instability of lysosomal membranes and releases various kinds of hydrolytic enzymes to lead further to cell damage. V.E might act on inhibiting lipid peroxidation to stabilize lysosomal membranes.


Etiology of cholesterol gallstones.

Formation of pure cholesterol stones is initiated by an excessive intake of highly purified carbohydrates, a large intake of animal fats and a restricted intake of vegetable fibers. When the protein content of the lithogenic diet was reduced, mixed or combined stones were formed in golden hamsters. These experimentally, dietarily produced gallstones had compositions and fine structures similar to those of human gallstones. Some mentions were made on black stones which were found in the aged golden hamsters fed with lithogenic diets.


Clinical studies on human pancreatic deoxyribonuclease I.

Duodenal juice collected after administration of Boot's pancreozymin and secretin to patients with various pancreatic diseases was subjected to deoxyribonuclease I (DNase I) assay, as well as measurements of total volume, amylase output and maximum bicarbonate concentration. It was observed that the DNase I output is well correlated with each of three factors. The DNase I output was much lower in patients with chronic pancreatitis or pancreatic cancer than in control subjects, and DNase I output was even found to be low in patients suspected of having chronic pancreatitis, who did not give abnormal resulsts with other assay methods. These results imply that DNase I output may be a good indicator of exocrine function of the pancreas, and thus may be useful for early detection of pancreatic diseases.


Assessment of the clinical usefulness of serum ribonuclease assays: an indicator for the detection of pancreatic cancer.

To evaluate diagnostic usefulness for pancreatic cancer, serum ribonuclease (RNase) level was determined in three groups of subjects; 1) normal volunteers as control, 2) patients with histologically determined pancreatic cancer, and 3) patients with miscellaneous diseases other than pancreatic cancer. A small increase of RNase values was recognized with age in the normal subjects and in the patients with nonpancreatic diseases, if renal function was normal. The mean RNase level in the control subjects was 97 +/- 41.2 units. A marked elevation of serum RNase level was demonstrated in the patients with pancreatic cancer (p less than 0.001) and in the patients with renal dysfuction, but no significant rise was noticed in the patients with pancreatitis. Mean values of RNase in the patients with pancreatic cancer and renal dysfuncton were 368 +/- 146 units and 342 +/- 78.1 units respectively. RNase values above 300 units were recognized in 15(71%) out of 21 patients with pancreatic cancer. Seven cases with elevated RNase over 300 units other than non-pancreatic malignancy and renal dysfunction were noticed in 6 instances of obstructive jaundice and in one instance of early gastric cancer (an 84-year-old male). The above-stated findings indicate that serum RNase determinations can be utilized as a diagnostic indicator for pancreatic cancer.


Interaction of secretin and glucagon on exocrine pancreatic secretion.

Inhibition of secretin-stimulated pancreatic secretion by glucagon was studied in anesthetized dogs. Two external pancreatic fistulas were prepared in dogs for both simultaneous and separate collection of pancreatic juice secreted by the right and left lobes. Two series of experiments were preformed. In the first, graded doses of glucagon (2.5 to 20 micrograms/kg/hr) were administered against a background infusion of 2 CHR U/kg/hr of secretin. In the second, a constant dose of glucagon (20 micrograms/kg/hr) was given against a background infusion of secretin doubling from 1 to 8 U/kg/hr. Infusion of glucagon was started when flow rate became nearly constant, and continued for 60 minutes in each dose. Glucagon produced the dose-related reduction in flow rate and bicarbonate secretion, but not in amylase secretion. This inhibitory effect was almost the same in size between the right and left lobes. No significant change of plasma secretin was observed during glucagon infusion. Michealis-Menten analysis of the dose in slopes (Km) and similar intercepts of Y-axis (CMR). These results suggest that glucagon inhibits competitively secretin-stimulated pancreatic secretion by acting probably on the same receptor as secretin.


RNase levels in golden hamster with DHPN induced pancreatic cancer.

Twenty Syrian golden hamsters recieved weekly injections of pancreatic cancer inducing DHPN. Their Poly (U) specific serum RNase levels were significantly elevated when compared to the control levels. Following salt fractionation, Poly (U) specific activity was present in both the 40% and 50% salt saturated fractions. Tissue assays showed that Poly (U) specific RNase was present in both pancreas and liver tissue extract, although the liver tissue RNase had a different pH maximum than that of the serum RNase.


Endoscopic analysis on the growth of early gastric carcinoma.

Earliest endoscopic appearance and its subsequent changes were studied in 41 cases of early gastric carcinoma where gastrocamera photographs were available for detailed analysis over the period from three months up to 10 years. The earliest appearance of polypoid carcinoma was a small area of nodularity, and that of carcinoma with mucosal depression was patchy reddening. Both types of carcinoma were thought to occur initially as a lesion without mucosal elevation or depression (IIb). In carcinoma with shallow mucosal depression (IIc and IIc-+III), there were cases believed to have remained intramucosal for an extremely long period of several years, whereas, in polypoid carcinoma (IIa and I), the growth seemed to be more rapid. In the cases with ulcer within the carcinomatous lesion, healing of the ulcer was confirmed in 37%, and "malignant cycles" were observed in 21%. Malignant transformation of gastric ulcer was suggested in one case with linear ulcer.


Determination of 15N-ammonia by chemical ionization mass spectrometry.

The tracing of ammonium nitrogen is important in hepatic diseases, especially in liver cirrhosis with hyperammonemia. In this paper, a new convenient method is described for determining stable isotope 15N-labeled ammonia using the Conway apparatus and chemical ionization mass spectrometry. The minimum quantity of ammonia necessary for reliable measure of 15N content was 0.1 muMol. The average error was 5.3%. In clinical application, 4 ml of blood after oral administration of 1 g of 15NH4Cl was sufficient for measurement.


High performance liquid-chromatographic analysis of individual bile acids: free, glycine- and taurine-conjugated bile acids.

High performance liquid-chromatographic analyses of individual bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid), free and conjugated with glycine and taurine, are described. The analyses of free and glycine-conjugated bile acids are based on esterification of carboxyl group of bile acids with O-(p-nitrobenzyl)-N, N'-diisopropylisourea (PNBDI). Moreover, ursodeoxycholic acid, hyocholic acid, hyodeoxycholic acid and 3beta-hydroxy-5-cholenoic acid also are able to analyse by this method. These bile acids in biological sample were extracted by an Amberlite XAD-2 column, and separated by DEAE-Sepharose CL-6B into free, glycine- and taurine-conjugated bile acids. After the separation, free and glycine-conjugated bile acids were esterified with PNBDI directly. Because taurine-conjugated bile acids are unable to be esterified with PNBDI, these bile acids were hydrolyzed by NaOH in order to make free bile acids, and then they were esterified. Because the p-nitrobenzyl ester of bile acids has characteristic ultraviolet absorption, these compounds were separated to individual bile acids by high performance liquid-chromatography, and detected by an UV-detector. An analysis of individual bile acids in human bile was demonstrated.


Review of five cases of limy bile--particularly on radiological, chemical and crystallographic studies--.

Incidence of "limy bile" is relatively rare and only 120 cases have been recorded in Japan so far. The present report is to add five more cases operated on at our clinic. On chemical analysis by atomic absorption spectrophotometry calcium carbonate was the major constituent of solid portion and ranged from 73.5 to 88.5%. On crystallographic analyses, the infrared spectra by means of KBr-disk method gave patterns of calcium carbonate in all cases, and the X-ray powder diffraction studies disclosed those of aragonite only in cases 2 and 4, and aragonite-calcite mixture in cases 1 and 3. The exact etiology of formation of limy bile in the gallbladder has not yet been understood completely.


Application of magnification radiography to the biliary system.

Magnification radiography was applied for the diagnosis of the biliary tract diseases including cancer. Our X-ray unit was consisting of HITACHI DR-155-23 U-6M-55P and 0.1 mm focal-spot tube, FFD 80 cm giving a magnification of x2 with the conditions of 60 kVp, 20 mA, 0.8 sec. Intensifying screens such as Kyokko LH II (for a standard sized subject) or DuPont Q II (for an obese subject) were used in combination with Fuji RX films. We confirmed a high diagnostic value in revealing early lesions of this sytem. The skin dose test indicated that this technique was routinely applicable with safety for clinical use.


A fluorescence histochemical study for the motility of the gallbladder.

For the purpose of elucidating the motility, particularly the mechanism of contraction of the gallbladder, we classified gallbladders isolated surgically into three groups for a study. That is, the three groups comprised Group I of 40 cases of cholelithiasis with good contraction, Group II of 10 cases of cholelithiasis with poor contraction and Group III of 10 cases of cholelithiasis after gastrectomy for a total of 60 cases. Using gallbladders of these cases, we started with a fundamental study on the autonomic nervous action by the fluorescence histochemical method of Flack and Hillarp and obtained results as follows. Similar results were obtained for Group I and Group II; the gallbladder was subjected to adrenergic innervation and cholinergic innervation, and there was a clear localized difference between true-cholinesterase and pseudo-cholinesterase of the cholinergic nerve. In Group III, proliferation of adrenergic nerve was observed compared with Groups I and II, while disappearance of cholinergic nerve was seen. The gallbladder of Group III showed slight contraction with cholecystokinin, but it was not blocked with atropine.


On the Mirizzi syndrome--benign stenosis of the hepatic duct induced by a stone in the cystic duct or the neck of the gallbladder.

Three cases of Mirizzi Syndrome are reported. One of them was induced by the stone in gallbladder remnant. On the cholangiogram, one case showed narrowing of common hepatic duct near the porta hepatis, and one case revealed a tapered narrowing-like stenosis. Those findings resembled malignancy but closer examination could differentiate this syndrome from malignancy. Selective angiography was useful to differentiate the syndrome from malignancy. Even in the cases where stricture is severe, exstirpation of gallbladder or cystic duct, freeing the anterior wall of extrahepatic bile duct from marked hyperplasia of fibrous tissues and insertion of a T-tube as an internal splint through the stenosis were effective. It is the opinion of the authors, therefore, that the reconstruction of a strictured bile duct may not necessarily be done by resection of stricture and a hepatojejunostomy.


Light and electron microscopic radioautography of rat stomach G-cells labeled with 3H-amino acids.

This paper reports light and electron microscope radioautographic studies of the sites of gastrin synthesis and the paths of intracellular migration of secretory granules in G-cells of rat glandular stomach incubated in vitro with 3H-glutamic acid and/or 3H-glycine at pH 8.2 or 2.5. Although the ultrastructural preservation of tissues maintained in pH 2.5 medium deteriorated within 30 minutes after beginning incubation, morphological observation was possible at least 60 minutes in the pH 8.2 medium. At 5 minutes, silver grains were few, and located chiefly over granular endoplasmic reticulum. After 30 minutes of labeling, silver grains were more numerous and found over the cytoplasm rich in secretory granules and over the nucleus. After incubation for 60 minutes, the distribution of silver grains was the same as at 30 minutes incubation but the labeling was heavier. Secretory granules of different sizes and electron densities were not differentially labeled. The following conclusions are drawn: (1) glutamic acid and/or glycine are incorporated in G-cells, synthesized into proteins and/or polypeptides in the rough surfaced endoplasmic reticulum and formed into secretory granules probably in the Golgi area: (2) the secretory granules thus formed migrate from the Golgi zone to the peripheral cytoplasm and are stored there; and (3) the kinetics of secretion in G-cells are fairly speedy under certain conditions.


Peripheral lymphocyte culture in the diagnosis of drug induced liver injury.

In order to evaluate the usefulness of the peripheral lymphocyte culture method for the diagnosis of drug-induced liver injury, a study was carried out on 21 cases of drug-induced liver injury (Group A). Nine cases in Group A showed a positive lymphocyte stimulation test. Out of 9 cases which showed positive stimulation six cases were cholestatic type of liver injury, and the remaining three were of hepatitic type. The results suggest that peripheral lymphocyte culture method is a useful method for diagnosis of drug-induced liver injury.


Early cancer of duodenal duplication. A case report.

A case which presented with early cancer of the duodenal duplication in addition to a gallbladder defect is reported. This may be the first case of its kind reported in the literature.


A case report of leiomyosarcoma originating in the ligamentum teres of the liver.

A case of leiomyosarcoma that appeared to have originated in the ligamentum teres hepatis of a 66-year-old female has been presented. The case was suspected of leiomyosarcoma originating in the ligamentum teres of the liver from the findings by preoperative examinations, and definitely diagnosed as such in a laparotomy and by histological examination of the resected tissue specimen.


Permselectivity of cat blood-lymph barrier to endogenous macromolecules.

The restrictive properties of liver blood-lymph barrier to endogenous plasma protein fractions of varying molecular size were studied at different hepatic venous pressures (and lymph flows) using steady-state lymph to plasma protein concentration ratios. At control hepatic venous pressures (0-2 mmHg) the lymph to plasma venous concentration ratios of the various protein fractions indicate significant selectivity by the liver blood-lymph barrier to macromolecules on the basis of molecular size. The sieving observed was consistent with equivalent pore radii of 180-250 A. The transsinusoidal oncotic pressure gradient ranged between 4.0 and 8.0 mmHg at control venous pressures. As venous pressure was increased, liver lymph flow and lymph to plasma protein concentration ratio increased while the blood-lymph oncotic pressure gradient decreased. Liver lymph flow was linearly related to hepatic venous pressure. At lymph flow less than or equal to 10 x control, there is no longer a sieving effect on plasma protein; findings consistent with por radii in excess of 1000 A. The results of this study suggest that maximal sieving by the liver blood-lymph barrier occur at normal capillary filtration rates and support the possibility that the interstitium is the rate limiting barrier for blood to lymph transport of macromolecules in the liver.


Gallbladder emptying in response to cholecystokinin. A cholescintigraphic study.

The threshold and dynamics of gallbladder emptying in human subjects in response to cholecystokinin (Pancreozymin, Boots Co. Ltd) were defined by radionuclide imaging with a gamma camera. The radiopharmaceutical employed, 99mTc-HIDA, was taken up rapidly by the liver and efficiently excreted into the biliary system so that gallbladder filling was easily distinguishable from negligible background activity. Counts were recorded continuously on magnetic tape during i.v. infusion of sequentially increasing doses of cholecystokinin: Each dose level was maintained for 15 min. At later playback, the area of interest was adjusted to include only the gallbladder and to exclude radioactivity present in the gut during gallbladder emptying. In 19 normal subjects (10 male and 9 female), a threshold dose of cholecystokin was identified for gallbladder contraction: 0.010 Crick-Harper-Raper units/kg-min in 16 subjects, and 0.020 Crick-Harper-Raper units/kg-min in the remaining 3. The rate of emptying appeared smooth and linear at each dose level: Doubling the dose of cholecystokinin in every case significantly increased the emptying rate. There appeared to be no effect of increasing age on emptying more rapidly than females, but the difference was not significant. This cholescintigraphic technique would appear to offer a simple, accurate, yet noninvasive method for continuously monitoring the events during gallbladder contraction in humans.


Unconjugated hyperbilirubinemia during treatment with chenodeoxycholic acid.

The authors describe a slight but significant increase in the serum levels of indirect-reacting bilirubin in gallstone patients after 3 and 6 mo of treatment with chenodeoxycholic acid. A return to pretreatment values was noted at 9 mo. The mechanism of this abnormality remains unclear. Two explanations are theoretically possible: a subclinical hemolysis or a modification of the hepatic transport and/or the conjugation of bilirubin.


Changes in polyamine metabolism of rat liver after administration of D-galactosamine. Favorable effects of putrescine administration on galactosamine-induced hepatic injury.

There are many reports showing a close relation between polyamine metabolism and tissue growth or recovery of damaged tissues, such as regenerating liver. Thus, changes in polyamine metabolism in the livers from rats treated with D-galactosamine, an inducer of experimental hepatitis, were studied. The activity of ornithine decarboxylase started to increase 14 hr after administration of galactosamine  and reached 30 times the normal activity at about 25 hr, the time of maximum severity of hepatitis. The content of putrescine increased to about 10 times the control value. After increases in the putrescine content and ornithine decarboxylase activity, the hepatitis started to diminish. Increases in the activity of S-adenosylmethionine decarboxylase and the content of spermidine were observed 33-37 hr after administration of galactosamine. The maximum values of these parameters, which were significantly higher than the control values, were observed after the healing process had started.


Endoprosthesis for internal drainage of the biliary tract. Technique and results in 48 cases.

In 48 patients with obstructive jaundice caused by unresectable lesions, a polyethylene tube was inserted into the biliary tract using a percutaneous transhepatic technique. This endoprosthesis provided permanent internal drainage without an external catheter. In 27 patients, bilirubin declined to anicteric or subicteric levels and pruritus subsided. In six patients, endoprosthesis had an intermediate effect, with moderate falls in bilirubin and improvement of their general condition. This method does not seem to increase the risk of percutaneous transhepatic cholangiography, which precedes insertion. It is recommended for patients with inoperable bile duct obstruction and may replace surgical biliodigestive anastomoses in patients with unresectable lesions.


The role of radiocopper in the diagnosis of Wilson's disease.

In patients with normal serum concentrations of ceruloplasmin, measurement of the incorporation of radiocopper into this protein can aid in the clinically important differentiation of patients with hepatic illnesses that mimic Wilson's disease from patients with this disorder.


Cimetidine hepatitis.

This case of an adult with cimetidine-induced hepatitis is presented. An etiologic role for the drug was strongly suggested when the patient developed transient hepatic dysfunction after two reexposures to cimetidine, which reverted promptly on withdrawal of the drug. The temporal relation between the administration of the drug and the development of hepatic dysfunction suggests that it is a hypersensitivity type of reaction.


Investigation of a patient with Hodgkin's disease and cholestasis.

A patient with the cholestasis of Hodgkin's disease was investigated. Our studies failed to relate the cholestasis to endocrine abnormalities. The patient had severely abnormal aminopyrine metabolism, suggesting more profound hepatocellular dysfunction than had previously been appreciated.


Familial juvenile polyposis of the stomach.

Innumerable polyps of the stomach were recognized in a 13-yr old girl. She had no extragastric polyps on roentgenographic and endoscopic studies. Her elder brother received a subtotal gastrectomy because of gastric polyposis at 14 yr of age. Their mother died of gastric cancer at 37 yr of age. Only these three subjects in this family had unusual brown hair and were low in normal intelligence. Polyps produced chronic and severe loss of both blood and protein, which resolved after a subtotal gastrectomy at 18 yr of age. Macroscopic and histologic observations of polyps in the resected stomach confirmed the diagnosis of juvenile polyposis. Both siblings are now in good health. Classification of this hereditary syndrome as a newly recognized entity, familial juvenile polyposis of the stomach, is proposed.


Clinical experience with total colectomy and endorectal mucosal resection for inflammatory bowel disease.

During the past 3 yr, 17 patients with chronic ulcerative colitis and 6 with Crohn's disease who had severe rectal and colonic involvement underwent excision of the rectal mucosa without removal of the rectal muscle in combination with total colectomy and cutaneous ileostomy as a 1- or 2-stage procedure. This operative technique has cured each of the patients of their primary colonic and rectal disease and has obviated many of the unpleasant complications that often occur after total proctectomy, such as impotence, prolonged perineal drainage, and bladder dysfunction. The operation has the further advantages of lower operative blood loss, shorter operative time, and earlier safe ambulation. On the basis of the favorable experience with mucosal proctectomy, sphincterotomy, and perineal drainage in 23 patients, none of whom experienced major complications, we believe that this operation warrants further clinical trial in patients with inflammatory bowel disease involving the rectum, which is refractory to medical therapy. Total proctectomy might eventually find scant application in patients with inflammatory bowel disease.


Serum gastrin during intestinal phase of acid secretion in dogs.

These studies were designed to determine whether the intestinal phase of gastric acid secretion is accompanied by an increase in serum gastrin concentration. Seven dogs with a gastric fistula and a duodenal fistula prepared so as to allow perfusion into the duodenum without reflux into the stomach were used. Gastric secretion and blood samples for serum gastrin determination were collected during intestinal perfusion with either 0.15 M NaCl or 5% liver extract at 200 ml hr(-1) for 2 hr. The mean +/- SE gastric acid secretory response during the second hour of perfusion with 0.15 M NaCl was 3.1 +/- 1.0% of the maximal acid output (MAO) to histamine, significantly (P less than 0.05) greater than the control value with no intestinal perfusion (0.18 +/- 0.07%). The mean +/- SE response during the second hour of perfusion with 5% liver extract was 7.4 +/- 2.2% of MAO, significantly (P less than 0.05) greater than both control and NaCl perfusion values. There was no significant change in peripheral serum gastrin concentration during the response to perfusion with either NaCl or liver extract. We conclude that, under the conditions of the present study, the intestinal phase of gastric acid secretion was not accompanied by an increase in serum gastrin concentration.


Structure of bile acids associated with secretion in the rat cecum.

An isolated in vivo rat cecal loop technique was utilized to determine what structure of bile acids is required to stimulate net colonic secretion of water and sodium. A dose response curve for water and sodium movement was determined for deoxycholic acid (1-6 mM) and chenodeoxycholic acid (3-6 mM). Both of these bile acids were associated with significant secretion of water and sodium at 4 mM concentration. Therefore, this concentration was used for all test bile acids studied. Test solutions included the tri- and di-substituted bile acids: cholic acid, hyocholic acid, 3 alpha, 7 beta, 12 alpha-trihydroxycholanic acid, 3 alpha, 12 alpha-dihydroxy-7-ketocholanic acid, ursodeoxycholic acid, 3 alpha-hydroxy-7-ketocholanic acid, 7 alpha, 12 alpha-dihydroxycholanic acid, and hyodeoxycholic acid. Only three bile acids, deoxycholic acid, chenodeoxycholic acid, and 7 alpha, 12 alpha-dihydroxycholanic acid were associated with net secretion of water and sodium. Cecal histology after incubation with bile acids revealed mucosal alterations in those sacs in which secretion occurred, but not where absorption was noted. These data indicate that bile acid-associated water and sodium secretion in the rat cecum requires a specific bile acid structure with a definite spatial relationship of the hydroxyl groups. Secretion occurred only with two alpha-hydroxyl groups in either the 3, 7, or 12 positions.


Elastic properties of the rectal wall in normal adults and in the patients with ulcerative colitis.

The elastic properties of the rectal wall have been studied in 16 normal adults (group I) and in 24 patients with ulcerative colitis, during a nonactive (13 cases, group II) or an active period (11 cases, group III). The rectal intraluminal pressures after accommodation to the distension were significantly higher in group III than in groups I and II. These pressures were not related to distending volumes in groups I and II but were correlated with the distending volumes in group III. The rectal elasticity coefficient was significantly greater in group III than in the other two groups. There was an inverse correlation between the rectal elasticity coefficient and the rectal area. These results suggest a loss of the rectal distensibility in active colitis.


Tertiary esophageal contractions evoked by acoustical stimuli.

"Spontaneous" tertiary esophageal contractions occur in a high proportion of healthy subjects. This study was carried out to investigate whether such contractions can be elicited by acoustical stimuli, to determine the threshold intensity at which contractions occur, and to find out how many of a sequence of equiintense tones at such a threshold intensity evoke contractile responses. Esophageal pressures were recorded 5, 10, and 15 cm above the lower esophageal sphincter, and swallowing was recorded by an electromyogram of the mylo-hyoid muscles. The results are summarized as follows: (a) All of 22 subjects exposed to 1000 Hz tones of intensities between 70 and 125 dBA responded with teritary contractions; their mean threshold intensity was 86.8 dBA +/- 3.0 SEM. Intensities that were 5 to 20 dBA higher were necessary to evoke contractions also in response to a second tone of a given intensity. (b) In 36 to 40 subjects exposed to 40 1000 Hz, 90 dBA tones tertiary contractions occurred in response to 47.2% of stimuli presented. (c) On repetitive stimulation, there was a significant decrease in number and amplitude of esophageal responses with an increasing number of stimuli. It is concluded that the esophagus takes part in the response system of the healthy organism to environmental stimuli.


Hepatic and pulmonary clearance of exogenous vasoactive intestinal peptide in the rat.

1125-labeled vasoactive intestinal peptide (VIP) has been injected into the portal and systemic circulations of rats in an attempt to identify the distribution and fate of the circulating peptide. When VIP I125 was introduced into the portal circulation radioactivity was concentrated in the liver (415.5% +/- 57.2 at 10 min--counts per minute (cpm) per gram of tissue as percentage cpm per milliliter of plasma). Radioactivity in kidney and lung was 346.6% +/- 37.4 and 136.4% +/- 11.4, respectively. In contrast, if the liver was bypassed by performing a portacaval shunt or by injecting into the inferior vena cava, radioactivity was maximal in the lung (2,454.3% +/- 302.3 10 min after IVC injection) with activity in the liver of only 89.3% +/- 10.6. Analysis of the pattern of radioactivity in plasma and tissue extracts by gel filtration chromatography showed the presence of a number of fragments of smaller molecular weight than VIP with a progressive diminution of the amount of VIP-like radioactivity. Both liver and lung have the capacity to concentrate VIP from the circulation. Vasoactive intestinal peptide released into the portal circulation is probably taken up initially by the liver, and this may prevent subsequent uptake by pulmonary tissue. There is some evidence to suggest that the liver and the lung may handle VIP in different ways. If this is so, the enhanced pulmonary extraction of VIP when the liver is bypassed may have some significance for the cardiovascular complications of fulminant liver failure.


Amylase to creatine clearance ratio in renal diseases.

In order to assess to what extent glomerular or tubular function is involved in the renal handling of amylase and the lysozyme to creatine clearance ratios (CAm/CCr and CLys/CCr) were evaluated in 22 healthy volunteers and in 71 patients with different renal diseases. In normal controls, the mean CAm/CCr was 2.55 +/-1.54 SD, with an upper normal limit of 5.56. A normal ratio was found in patients with glomerulonephritis, with or without a nephrotic syndrome, and in patients with pyelonephritis. A significantly elevated ratio (P less than 0.001) was instead found in patients with uremia and in patients with uremia and in patients with either chronic or acute tubular damage. The CLus/CCr ratio was elevated in all the groups, except in patients with glomerulonephritis and minimal proteinuria. These results show that in humans, as in animals, the amylase filtered load undergoes partial tubular reabsorption. In renal diseases, an increase of the CAm/CCr is caused by either a marked reduction of functioning nephrons or a severe tubular damage, while the glomerular permeability does not seem to be involved. Some other mechanism is probably involved in the elevation of the CAm/CCr during acute pancreatitis.


Effect of ninety-five percent pure cholecystokinin on gastrin-stimulated acid secretion in man and dog.

In 5 human subjects, 95% pure cholecystokinin (CCK) given as a background infusion in doses of 42, 84, or 168 pmol kg-1 h-1 did not significantly alter acid secretion in response to graded doses (11-300 pmol kg-1 h-1) of synthetic human gastrin-17-I. The 168 pmol kg-1 h-1 dose of CCK produced maximal pancreatic amylase output. In 3 subjects, 337 pmol kg-1 h-1 of CCK slightly stimulated acid secretion when given alone and tended to reduce acid secretion in response to gastrin, but each of the subjects experienced cramping abdominal pain. The increment in acid secretion produced by CCK alone was similar to that produced by maximally effective doses of carboxyl-terminal octapeptide of CCK. In dogs with gastric and pancreatic fistulas, 168 pmol kg-1 h-1 of CCK produced maximal pancreatic protein output and slightly stimulated gastric acid secretion. In dogs with gastric fistulas and Heidenhain pouches, the lowest dose of CCK that inhibited gastrin-stimulated acid secretion was 674 pmol kg-1 h-1. We conclude that in man and dog 95% pure CCK weakly stimulates gastric acid secretion and inhibits gastrin-stimulated acid secretion but these actions occur only with doses of CCK that are maximal or supramaximal for pancreatic enzyme secretion. Because of the high dose requirement, these effects are unlikely to be physiologically significant.


Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis.

The effect of moderate cirrhosis on the bioavailability and systemic clearance of three model analgesic compounds (pethidine, pentazocine, and salicylamide) with substantial first-pass metabolism was examined in 8 cirrhotic subjects and 4 agematched healthy controls. There was a 46% decrease in the clearance of pentazocine and a 278% increase in bioavailability. The corresponding figures for pethidine were 36% and 81%. The area under the plasma curve after oral salicylamide was increased by 551% in cirrhotic subjects compared with controls. This study demonstrated that drugs with the highest hepatic clearance will have the largest relative increases in bioavailability in cirrhotic patients due to portosystemic shunting. The decrease in clearance and increase in bioavailability will have multiplicative, rather than simply additive, effects on total area under the curve and, if related, pharmacologic response.


Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease.

Renal function is known to be abnormal in patients with cirrhosis. Diminished cortical blood flow due to active renal vasoconstriction is present. Renal prostaglandins, potent vasodilators, could be released by the kidney in an attempt to maintain renal blood flow. This possibility was investigated by measuring the effect of indomethacin, an inhibitor of prostaglandin synthetase, in patients with alcoholic liver disease. Administration of indomethacin reduced the effective renal plasma flow (ERPF) and creatinine clearance by 23% and 19%, respectively (P less than 0.001), and increased serum creatinine by 29% (P less than 0.001). The response to indomethacin was variable (fall in ERPF (+)7.8% to (-)67%), but was greatest in patients with ascites. Eighty percent of ascitic patients had a greater than 15% fall in ERPF after administration of indomethacin compared with 20% of nonascitic patients (P less than 0.025). An infusion of prostaglandin A1 in 13 patients corrected the decrease in ERPF and creatinine clearance that had followed the administration of indomethacin. The administration of indomethacin caused a significant fall in plasma renin activity, 8.2 +/- 2.5 to 3.6 +/- 1.4 ng/ml/hr (P less than 0.025). The fall in plasma renin activity occurred when ERPF was depressed maximally, suggesting that endogenous prostaglandins exert more control over renin release than does ERPF. Prostaglandins appear to be an important factor in maintaining renal blood flow in patients with cirrhosis and sodium retention.


The effect of chenodeoxycholic acid (CDCA) on cholesterol absorption.

The effect of administration of chenodeoxycholic acid (CDCA) on cholesterol absorption has been investigated in 11 volunteers. Five hundred milligrams of cholesterol 5 muCi of C14 cholesterol, and 10 muCi of H3 sitosterol (as a nonabsorbable marker) were given with a standard meal. Feces were collected for 6 days and cholesterol absorption was estimated from the recovered C14 radioactivity. The study was repeated after 20 days of treatment with CDCA. Cholesterol saturation of bile and biliary bile acid composition were also studied. Percent CDCA in bile was 40.5 +/- 14.0 SDM before treatment and rose to 75.3 +/- 5.7 after treatment. Saturation index fell from 1.08 +/- 0.31 to 0.71 +/- 0.19. Cholesterol absorption was 33.2 +/- 11.0% of the administered dose in basal conditions and decreased to 14.9 +/- 9.7% after treatment (P less than 0.01). In all but 1 subject, CDCA administration was associated with a decreased intestinal transit time. In conclusion, in doses effective to desaturate bile, CDCA seems to decrease dietary cholesterol absorption. This effect could contribute to the desaturation of bile observed during treatment with this bile acid for dissolving gallstones.


Hyperammonemic coma after hepatectomy in germ-free rats.

Current theories on the pathogenesis of hepatic coma indicate that intestinal bacteria produce cerebral toxins, such as ammonia, mercaptans, and short-chain fatty acids. To test the hypothesis that elimination of anaerobic and aerobic intestinal bacteria retards the onset and alters the biochemical profile of acute hepatic coma, we determined the onset of coma and the ammonia concentration in blood and cecal contents in 7 germ-free and 10 normal dehepatized rats. Ammonia levels were also determined in a further group of 7 germ-free and 12 normal rats 24 hr after hepatic vascular exclusion was accomplished. Onset of coma for germ-free rats (x: 34 hr) was identical to that of normal rats (x: 36 hr). Arterial ammonia was equally elevated in germ-free rats (x: 834 mumol/liter) and in normal rats (x: 854 mumol/liter), although the ammonia concentration in the cecal contents was significantly lower in germ-free rats (x: 1762 mumol/liter) than in normal rats (x: 5572 mumol/liter). In germ-free animals, portal venous blood contained more ammonia than arterial blood (x A-V difference: -87 mumol/liter), indicating nonbacterial intestinal ammonia release. We conclude that intestinal bacteria toxins are of minor importance in the mechanism of acute hepatic coma of the liverless rat and that presumably bacterial toxins, such as ammonia, can be products of nonbacterial metabolism. Since hyperammonemia could be considered an important determinant of coma in our model, prevention of hyperammonemia in functionally anhepatic animals should be the next objective in unraveling the pathogenesis of acute hepatic coma.


The renal and hemodynamic effects of the peritoneovenous shunt for intractable hepatic ascites.

Fifteen patients with chronic liver disease having a peritoneovenous shunt for chronic intractable ascites were studied prospectively for renal function and hemodynamic changes during balance studies, pre-, peri-, and postoperatively. Shunt insertion caused a rapid redistribution of ascites into the intravascular compartment with hemodilution and significant rises in cardiac output (9 patients) (P less than 0.025) renal blood flow (3 patients) (P less than 0.025), and creatinine clearance (15 patients) (P less than 0.005), and decreases in plasma renin activity (10 patients) and serum aldosterone levels (9 patients) (P less than 0.025). Despite these changes, small repeated doses of furosemide were required to start and maintain a diuresis and natriuresis with sodium excretion rising from 7.2 +/- 4.1 to 174 +/- 44 meq/day (P less than 0.0005) in the 15 patients. At 2 wk postoperatively, the 15 patients had lost a mean of 7.5 kg in weight associated with a persistent improvement in creatinine clearance and a continued natriuresis, 15.9 +/- 7 mEq/day (P less than 0.005), despite no statistically significant change in cardiac output (7 patients) or renal blood flow (4 patients) compared with preoperative levels. This operation is an effective therapy for refractive ascites, but the incidence of potentially fatal complications makes us hesitate to recommend it except for patients resistant to normal conservative measures.


Ultrasonic properties of gallstones. Effect of stone size and composition.

In vivo and in vitro ultrasonic characteristics of gallstones were compared with stone size and composition with the aim of understanding the basis for these features. In vivo and in vitro ultrasonic features of the same stone were identical. Acoustic shadowing was not due to stone type, radiodensity, or calcium content. However, all stones larger than 4 mm in diameter produced a distinct sonic shadow. Gallbladder sludge produced internal echoes without a sonic shadow. These echoes shifted slowly when the patient was reexamined in a different position. Four of seven cholesterol stones containing more than 88% cholesterol floated and produced a sonic shadow without internal echoes or with an area of internal echoes within the gallbladder at a distance from the posterior wall. This last feature may identify patients that are good candidates for a trial of gallstone dissolution with chenodeoxycholic acid.


Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment.

Malabsorption of bile acids is known to occur in patients with pancreatic insufficiency particularly when due to cystic fibrosis. Abnormal biliary secretion or intraluminal acidic precipitation of bile acids could contribute to the steatorrhea of pancreatic insufficiency. To measure bile acid outputs and duodenal concentrations of bile salts and lipids simultaneously, we performed intestinal intubation and perfusion studies during feeding of a solid test meal in 6 healthy controls and 8 adult patients with advanced acquired exocrine pancreatic insufficiency. The effects of various treatment regimens were also investigated. Postprandial bile acid secretion was similar in all treatment groups. However, significant (P less than 0.05) reductions in micellar concentrations of bile acids and fatty acids were observed in untreated pancreatic insufficiency. These abnormalities were directly related to pH-induced precipitation of bile acids and were corrected only by the addition of cimetidine to standard pancreatin therapy. Thus, in pancreatic insufficiency, treatment with pancreatin plus cimetidine enhances fat digestion and absorption by reducing both acid-peptic inactivation of lipase and acidic precipitation of bile acids.


Cancer in universal and left-sided ulcerative colitis: factors determining risk.

A retrospective study of 267 patients with ulcerative colitis admitted to The Mount Sinai Hospital during the period 1960--1976 revealed 26 (9.7%) with adenocarcinoma of the colon. Twenty-one cases of colorectal cancer were observed among 158 patients with universal colitis (13%), and 5 occurred among 109 patients with left-sided disease (5%). Patients with left-sided disease tended to develop cancer at least a decade later than patients with universal disease. The median duration from onset of colitis to diagnosis of cancer was 20 yr for those with universal colitis, and 32 yr for those with left-sided colitis. The decade incidence of colorectal carcinoma increased from 0.4% in the first decade to 7.4% in the second, 15.9% in the third, and 52.6% in the fourth decade of follow-up. The estimated cumulative probability of developing cancer reached 34% at 30 yr and 64% at 40 yr. Cancer risk was positively correlated with duration and anatomic extent of colitis, but did not appear to be increased by early age at onset of disease.


Antibiotic associated pseudomembranous colitis with negative proctosigmoidoscopy examination.

Most investigators have stressed that the diagnosis of antibiotic associated pseudomembranous colitis is made by proctosigmoidoscopic examination. In our investigation, 6 patients with tissue culture evidence of a clostridial toxin in stools and either normal or only edematous rectal mucosa were studied with total colonoscopy. Five of six patients demonstrated pseudomembranes located in various areas of the colon at a time when the rectosigmoid area was uninvolved. This demonstrates the occurrence of antibiotic associated pseudomembranous colitis which can be missed by routine proctosigmoidoscopy. The incidence of rectal sparing in this disease remains undetermined. Further investigation to determine the occurrence of antibiotic colitis, response to different treatments, or sensitivity of tissue culture assays as a diagnostic aid in antibiotic associated pseudomembranous colitis must take this subgroup into account.


Effects of water-immersion stress on gastric secretion and mucosal blood flow in rats.

The correlation between acid secretion and mucosal blood flow in the rat stomach during stress loading was determined to provide clues to the etiology of the gastric ulceration which thus occurs. The gastric acid output was increased remarkably by water-immersion stress at 23 degrees C, and this increase lasted while the stress was given, yet the mucosal blood flow did not show a corresponding increase. In rats stressed for 3 hr, ulcerative changes were observed in the glandular portion of the stomach. The stress-induced increase in acid output correlated well with the severity of erosions. Pretreatment of animals with atropine 10 microgram/kg, given subcutaneously, or vagotomy, inhibited the increase in acid output and also inhibited the ulcer formation caused by the stress: however, the mucosal blood flow in these animals decreased significantly. These results suggest that when there is an elevation of gastric acid secretion with no parallel increase in mucosal blood flow, gastric ulceration may occur under conditions of stress.


Increased resistance of the gastric mucosal barrier to barrier breakers in the rat.

The effects of two exposures of the gastric mucosa to either 10 mM taurocholic acid (TcA) or 20% ethanol, both in 150 mM HCl, on transmucosal potential difference (PD) and net fluxes of H+, Na+, and K+ ions have been tested in the rat. The interval between exposures was 30 min. The results demonstrated that the first exposure of the gastric mucosa, either to TcA or to ethanol, reduced the net fluxes of H+, Na+, K+ and the change in transmucosal PD induced by the second exposure, indicating an increased resistance of the mucosa to the barrier breaking effects of TcA or ethanol.


Effect of bilateral cervical vagotomy on balloon-induced lower esophageal sphincter relaxation in the dog.

A study was performed in dogs to determine whether balloon distension within the striated muscle esophagus induces lower esophageal sphincter relaxation via a local intramural pathway or a central neural pathway. Bilateral vagosympathetic nerve blockade was produced by cooling the nerve trunks isolated in skin loops on either side of the neck. Sphincter pressure was measured before and during intraesophageal balloon distension, with and without nerve blockade. With the vagosympathetic nerves intact, balloon distension produced sphincter relaxation, sphincter shortening, and orad movement of the sphincter. The threshold for these responses increased progressively as distension was applied at more proximal levels. Bilateral vagosympathetic nerve blockade abolished all the lower esophageal sphincter responses to distension at any level within the esophagus, whether or not sphincter pressure was raised by pentagastrin infusion. Therefore, lower esophageal sphincter relaxation induced by distension of the dog striated muscle esophagus requires a central nervous system connection via the vagosympathetic nerve trunks. There is no direct intramural pathway for this responses in the dog.


Rectoanal pressures and rectal sensitivity studies in chronic childhood constipation.

Rectoanal pressures and rectal sensitivity studies were performed in 32 control children and 144 chronically constipated children. The rectoanal inhibitory reflex threshold, the maximal anal resting closure pressure, and the conscious rectal sensitivity threshold were studied in these children. The rectoanal inhibitory reflex threshold was increased in 6.2% of the constipated patients. Anal hypertony (increased maximal anal resting pressure) was found in 46% of the constipated children. Decreased rectal sensitivity (increased conscious sensitivity threshold) was found in 68% of the constipated children. The three parameters were found to be normal in only 13% of the constipated subjects. Thus, it appears that children with chronic constipation who do not have Hirschsprung's disease do have abnormalities at manometry in most cases.


Expanded linkage map of Vibrio cholerae.

An expanded linkage map of the Vibrio cholerae classical strain 162 chromosome has been prepared using a variety of new auxotrophic mutants. The chromosome consists of a single, linear linkage group. The map consists of 17 markers, which have been ordered; 20 mutational sites, which are tentatively ordered; five markers (ura-1, ser-2, mal-1, man-1, suc-1), which are linked but unordered; and three mutations (aro-2, cys-2 and cys-6) which showed little or no linkage. A proposal is made to standardize genetic nomenclature in V. cholerae genetic studies.


Use of two-dimensional electrophoresis to identify and map new mouse genes.

Cytosol polypeptides from mouse liver have been examined using two-dimensional electrophoresis. About 250 spots were readily discernible. When cytosols from strains BALB/cBy and C57BL/6By were compared eight genetically determined differences were observed. Other strain pairs show comparable numbers of differences. These eight phenotypes were scored in seven recombinant inbred lines derived from the two parental strains, and their strain distribution patterns were compared with previously determined patterns for other genetic markers that differ between the two progenitor strains. Using this information, tentative chromosomes assignments for the genes controlling five of the variant phenotypes have been made, and two of the assignments have been confirmed using congenic resistant strains. These eight genes will be useful reference markers in future crosses designed to map new genes.


Current concepts in managing TIAs and stroke.

No permanent neurologic deficit results from a transient ischemic attack, but patients with these episodes are at risk of stroke. Successful treatment depends on identifying the source of the problem--the heart, blood, or vessel wall. However, anticoagulants and antiplatelet agglutinating agents will reduce only the incidence of TIA's, not the incidence of stroke. Prompt vigorous treatment of progressive stroke may avert completed stroke. Heparin is recommended, unless a specific etiologic factor, such as polycythemia or hypertension, is identified.


Guard against unpredictable drug responses in the aging.

Altered and unexpected responses to treatment can be caused by physiologic changes that occur with aging. These changes can affect the absorption, distribution, metabolism, and elimination of drugs. Changes in renal function, body composition, and the gastrointestinal tract are variables influencing a drug's mechanism of action. To avoid therapeutic problems, understanding these variables is essential.


Tips on prescribing exercise regimens for your older patient.

A sedentary life style may contribute as much to functional losses in the elderly as the aging process itself. In a series of studies involving over 200 older men and women over a period of 5 years, carefully prescribed exercise resulted in significant physiologic improvement. Healthy older subjects can be trained in relatively the same way as younger people, but the hazards of endurance training are greater. Medical screening, individual assessment of exercise response, and careful progression in training challenge are essential.


Helping an aging patient to cope with memory problems.

Memory loss is often a subjective symptom rather than an objective one. Complaints of poor memory appear to be related to stereotypes of aging and to the presence of depression, rather than to chronic brain disease. Reassuring an elderly person that occasional forgetfulness does not indicate senility, and improving morale in those who are depressed, effectively reduce exaggerated memory concerns.


When and how to use heparin prophylaxis and treatment.

Heparin is a naturally occurring anticoagulant drug that combines with anti-thrombin III to inhibit many steps of the coagulation pathway. Clinically, heparin is used in small doses to prevent venous thrombosis and pulmonary embolism; in large doses, it is the treatment of choice in acute venous thromboembolism. Heparin also is used to treat some acute arterial thromboembolic episodes. Heparin may be given by intermittent intravenous injection or continuous intravenous infusion, usually in doses of approximately 30,000 units per day. Hemorrhage, the main side effect of heparin, appears to be less frequent when therapeutic doses are given by continuous intravenous infusion rather than by intermittent intravenous injection.


Clinical evaluation of renal lithiasis.

Determining metabolic activity in urolithiasis may avoid excessive laboratory tests and unnecessary treatment. A simple regimen such as increased oral fluids is often effective therapy in metabolically inactive disease. Most cases of renal lithiasis are idiopathic, but a complete examination and laboratory work-up will usually establish an accurate etiologic diagnosis.


Guidelines for evaluating and treating hypertension.

Any patient with elevated blood pressure on at least two occasions should have a hypertensive workup; however, extensive evaluation for a correctable cause of hypertension is seldom necessary unless findings in the history, physical examination, or basic laboratory tests are abnormal. Diuretics are the cornerstone of therapy. If blood pressure does not respond adequately to these agents, a step-care approach with more potent antihypertensives is indicated.


A diagnostic approach to occult blood in the stool.

Occult blood in the stool may be the first sign of otherwise asymptomatic colorectal cancer or other gastrointestinal disease. All patients over 40 should therefore have a rectal examination that includes a Hemoccult slide test. A rational diagnostic plan is essential to identify the source of occult blood in the stool. Most gastrointestinal cancer is operable if diagnosed early, so early detection of these lesions is imperative.


The painful hip: helping the handicapped cope.

When seeing a patient with unexplained knee pain, it is imperative to examine and study the hip. Careful examination and maintaining notes on the patient's ability to walk and to perform daily functions will help determine when and if surgical treatment should be advised. Early consultation with an orthopedic surgeon will frequently be useful in determining whether an intertrochanteric osteotomy of the femur, a resurfacing operation of the hip, or a total hip replacement is indicated. From the orthopedist's point of view, it would be preferable to see the patient when at least 70 degrees of flexion is present. Although intertrochanteric osteotomy is rarely performed in the United States, it is the most common operation for uncomplicated coxarthrosis performed in Europe, and, when done at the right time, can provide the patient with an additional 10 to 15 years of use of his own hip. Resurfacing operations for the femoral head and acetabulum are valuable, if temporary, measures for treating arthritis in the younger patient; for the older patient, total hip replacement is preferred.


The granuloma in Crohn's disease.

The number of granulomas in sections of bowel involved by Crohn's disease has been counted and related to length of previous history, treatment with steroids, site of involvement, and the subsequent course of the disease. It was found that a high content of granulomas predicted a good prognosis in the large bowel and anus, but was of no prognostic significance in the small bowel. A large regional variation in granuloma counts was observed from an average of 1 per section in the small bowel to 6 in the colon, 18 in the rectum, and 36 in the anus. Those patients with a long clinical history showed a low granuloma content. The findings are consistent with the view that the granuloma represents an adaptive mechanism for the removal or localisation of the causative agent of Crohn's disease.


Endoscopic retrograde brush cytology in patients with primary and secondary malignancies of the pancreas.

Endoscopic retrograde brush cytology (ERBC) was performed in 29 patients with primary pancreatic malignancies verified later by histology. Results were positive in 21 patients, suspicious in five, and negative in three. ERBC performed in seven patients with uncertain findings at endoscopic retrograde cholangiopancreatography (ERCP) was positive for malignancy in six and suspicious in one. Endoscopic aspiration cytology (EAC) performed in 10 patients with primary tumours was positive for malignancy in three, suspicious in two, and negative in five cases. ERBC and/or EAC performed in five cases with secondary tumours were positive for malignancy in one and negative in four. It is concluded that ERBC gives a high rate of positive or suspicious (90%) diagnosis of malignancy in patients with primary pancreatic lesions. In secondary tumours cytology seems to be negative in most cases. The study further shows that many of the malignant tumours found by ERP are secondary lesions. Cytology is often able to detect malignancy when ERP has proved inconclusive.


Transnasal bile duct catheterisation after endoscopic sphincterotomy: method for biliary drainage, perfusion, and sequential cholangiography.

We describe a method for leaving a catheter in the common bile duct for several days, even weeks, after endoscopic sphincterotomy. This provides reliable biliary drainage, and permits perfusion of the duct with simple fluids or solvents. It reduces the need for instrumental stone extraction and for repeated endoscopy and cholangiography to check whether stones have passed, since transnasal cholangiograms can be performed simply and repeatedly without discomfort.


Comparison of oral feeding of peptide and amino acid meals to normal human subjects.

Intestinal perfusion studies performed in man have suggested that amino acid nitrogen may be absorbed more rapidly from peptides than free amino acids. The aim of the present study was to compare the effects of the oral administration of peptides and free amino acids. Two isonitrogenous liquid test meals, one containing 50 g of a partial enzymic hydrolysate of fish protein in which approximately 80% of the nitrogen content was present as small peptides (peptide meal), and the other a mixture of free amino acids (amino acid meal) the composition and molar pattern of which simulated that of the peptide meal, were administered on separate occasions to six normal subjects intubated with a triple lumen tube. Both meals contained the reference marker polyethylene glycol. Fractional absorption of amino acid residues one and two hours after ingestion of the two meals was similar at three intestinal locations situated 120, 160, and 200 cm from the mouth of each subject, and at two hours 73.8% and 72.0% of the amino acid residues had been absorbed respectively by the time the contents of the peptide and amino acid meals reached the middle sampling port of the tube. The total sum of individual amino acid increments in plasma was significantly greater 30 minutes (p < 0.025) and one hour (p < 0.05) after ingestion of the peptide than amino acid meals. By three hours the total area under the two plasma curves was similar. Normal human subjects thus appeared to be capable of assimilating orally administered mixtures of peptides and free amino acids with equal efficiency. Secretion of fluid into the lumen of the upper small intestine, assessed by reference to dilution of the polyethylene glycol, was less after ingestion of the peptide meal. In clinical situations characterised by fluid and electrolyte malabsorption consideration might be given to using small peptides rather than free amino acids as the nitrogen source in nutritional diets.


Nippostrongylus brasiliensis infection in the rat: effect of iron and protein deficiency on the anthelmintic efficacy of mebendazole, pyrantel, piperazine, and levamisole.

The benzimidazole anthelmintics mebendazole and fenbendazole have been shown to be much less effective against Nippostrongylus brasiliensis infections in the rat on a combined iron and protein deficient diet. In the present experiments it was shown that the anthelmintic efficacy of mebendazole was significantly impaired in the rat on either an iron deficient or a protein deficient diet. Furthermore, iron and protein deficiency reduced the efficacy of the anthelmintics pyrantel and piperazine but not levamisole. The finding that nutritional deficiencies reduce anthelmintic efficacy may well be relevant to worm eradication programmes in iron deficient and protein calorie malnourished populations.


Proximal stomach and antrum in stomach emptying.

In a series of measurements of liquid-phase gastric emptying using a radionuclide marker on 35 subjects, five were identified in whom the proximal stomach and antrum were clearly distinguishable. Three of these subjects were normal controls and two suffered from systemic sclerosis. In the three normal subjects, analysis of the movement of the liquid showed the expected movement from fundus to antrum and thence through the pylorus. In the two patients with systemic sclerosis, there was, in contrast, evidence of mass retropulsion of the contents of the antrum into the fundus. In such cases, the measurement of stomach emptying based on the assumption of a single-compartment system in likely to be misleading.


Rowachol--a possible treatment for cholesterol gallstones.

It has been claimed that Rowachol, a proprietary choleretic, is occasionally successful in the treatment of gallstones. In gallstone patients we have examined its effect on the lipid composition of (1) samples of fasting gall bladder bile obtained at the time of cholecystectomy, and (2) T-tube bile on the tenth post-operative day. In a dose of two capsules, three times a day for only 48 hours, Rowachol significantly lowered the cholesterol solubility of both gall bladder (P less than 0.001) and T-tube bile (P less than 0.05). Rowachol in a dose of one capsule three times a day for 48 hours did not alter bile composition, while four capsules four times a day for a similar period caused a significant (P less than 0.05) deterioration in biliary lipid composition. The possible mechanisms of action of Rowachol and their therapeutic implications are discussed.


Chronic non-specific ulcerative duodenojejunoileitis: report of four cases.

Four patients with chronic non-specific ulcerative duodenojejunoileitis (CNSUDJI) are reported. The clinical picture included abdominal pain, fever, and a malabsorption syndrome. Main rediological findings were diffuse narrowing of the jejunal loops with total effacement of the mucosal folds. Multiple peroral biopsies of the small intestine showed various degrees of mucosal abnormalities from total villous atrophy to normal villi, but ulcerations were diagnosed only by operative full thickness biopsies or resection of the small bowel. The ulcerative process was associated with well-documented coeliac disease in two patients: in one of them it occurred as a fatal complication involving also the colon, three years after the start of a gluten free diet, while the disease was in full clinical and histological remission. In the other case, coeliac disease was revealed by obstructive symptoms due to stenosing ulcerations; five months after surgical resection of the stenosis, institution of a gluten free diet induced a dramatic improvement. In the two other patients ulcerations were not associated with coeliac disease: one of them had a patchy villous atrophy and resisted a gluten free diet and total parenteral nutrition; she was improved by and dependent upon steroids but finally died. The last patient had normal villous height; ulcerations were located exclusively along the mesenteric border of the small bowel; he had a low-grade protracted evolution resisting any form of therapy and developed a peripheral neuropathy of unknown aetiology. On the basis of our cases and of a review of the literature the discussion focuses on the difficulty in diagnosing CNSUDJI, its relationship with coeliac disease, and its management and prognosis.


On the problem of variable numbers of hosts in the life-cycles of helminths.

The authors analyze the phenomena underlying the variation of host numbers in the life-cycle of several helminth species. Variation of host number in the cycle is effected by alternative shortening of the cycle (with this the cycle turns out either without or with a polyvalent obligatory host or, in rarer cases, without or with appearing of neogeny) or by facultative widening of the cycle (without or with participation of additional hosts, namely para-paratenic, paradefinitive, metaparatenic, or euparatenic hosts). The term of metaparatenic host is made precise by limitation to a "hemistadiogenous" additional host (sensu Barus and Rysavý 1977).


Tissue reaction in the heart of cattle with a spontaneous and artificial Cysticercus bovis infection.

Results of detailed studies on tissue reactions to Cysticercus bovis in the heart of cattle, together with a comparison of findings in animals with spontaneous and experimental infection, and an evaluation of tissue reactions in relation to the location, morphology and morphogenesis of C. bovis provided evidence for the fact that in general, the response of the heart to the presence of C. bovis was an inflammatory reaction characterized by the origin of a pseudoepithelial border and a zone of granulation tissue. Later, when necrotic changes started to affect the cysticercus, the inflammatory reaction started to develop anew. It was accompanied by an exudation and a subsequent resorption. Characteristic features were focal necroses both of the exudate and the inflammatory border followed by a dystrophic calcification, focal necroses and a dystrophic calcification of individual collagenous fibres and groups of these fibres in addition to a regular appearance of necrotic-like foci typical of a reaction to C. bovis. The location of the cysticercus in a certain part of the lymphatic system of the heart and in skeletal muscles was shown to have a considerable effect on the course of the inflammatory reaction. Differences in the development of the inflammatory reaction explained concomitant findings of dead and live cysticerci at the same time after an experimental infection.


Persistence of Coxiella burnetii in beetles. Dermestes maculatus (Dermestidae).

Coxiella burnetti persisted irregularly in the larvae, pupae and imagos of Dermestes maculatus till 8th week after oral infection. Coxiella was probably transmitted between individual developmental stages by passages in the digestive tract.


Serologic examination of human population in South Moravia (Czechoslovakia) on the presence of antibodies to arboviruses of the Alfavirus, Flavivirus, Turlock groups and Bunyamwera supergroup.

A statistically representative group of human population from the South Moravian region (CSSR) was examined on the presence of antibodies against the following arboviruses: Lednice, Sindbis, tick-borne encephalitis, West Nile, Tahyna and Calovo. The ascertained absence of antibodies to the Lednice virus is an evidence that at present this virus is of no epidemiological importance in the region studied. No antibodies to Sindbis, West Nile and Calovo viruses were demonstrated. 17.8 to 42.0% of antibodies to Tahyna virus were detected in all age groups examined. The total infection rate was 26.0%. Antibodies to the tick-borne encephalitis virus occurred primarily in persons over 40 years. The total infection rate was 5.5%.


A proposal for the evaluation of vertebrates as to their role in the circulation of arboviruses.

The authors present a proposal for the classification of vertebrates as hosts or hosts-amplifiers of arboviruses from an ecological point of view.


Density gradient centrifugation for separation of different stages of Toxoplasma gondii.

Suitable procedures for separation of various stages of Toxoplasma gondii by density gradient centrifugation have been delineated using peritoneal exudate of infected mouse as a model. Separation from host cells was effected by gradient centrifugation at 450 g for 30 minutes. Using Ficoll, dextran and sucrose, average parasite recoveries by pooling up to and including the peak fraction of 73.65%, 66.18% and 65.68% respectively were obtained. Toxoplasma trophozoites peaked at density of 1.040 g/ml with Ficoll, 1.060 g/ml with dextran and 1.110 g/ml with sucrose. In view of successful separation of exo-enteric stages of Toxoplasma by density gradient centrifugation, possible application of this method to isolation of various endo-enteric stages is discussed.


Mammals as source of ectoparasites in towns.

Four ecological groups of mammal ectoparasites are recognized in urban environment and their medical importance is briefly mentioned.


Rib-cage injuries indicating the direction and strength of impact.

The hardness and loading capacity of hundreds of rib pairs have been tested and compared with the results of about 200 tests concerning belt-protected human cadavers. Rib fractures exhibit patterns that indicate the direction and strength of impact. Differences are seen between static and dynamic loading. Deformation of the loaded rib cage can be demonstrated by X-ray examination.


The species identification of very old human blood-stains.

The efficiency of 5% ammonia as an extractant of proteins from human bloodstains has been compared with that of water. Ammonia was shown to be a better extractant of protein than water and this allows the species identification of human bloodstains up to four years' old using conventional electrophoretic techniques.


Death due to anaphylactic reaction, with presentation of pertinent biochemical parameters. A case report.

Autopsy findings in a young worker point to acute anaphylaxis. The conclusion was supported by a number of biochemical parameters in the blood collected after death. The nature of the antigen involved could not be established. However, the data collected may be useful in the future evaluation of similar cases.


[Hygiene in children and adolescents].

Feminine hygiene is a concern not only in the reproductive years, but should be observed throughout life. Childhood is the formative period for behavior and every day routine, thus proper education and guidance of little girls are essential. Recognizing the importance of good personal hygiene habits for the prevention of diseases, the medical doctor should advise and motivate wherever possible.


Forensic application of rapid analysis of carboxyhemoglobin in blood using an oxygen electrode.

Blood carboxyhemoglobin (HbCO) levels in forensic victims were measured by a new and rapid oxygen-electrode method for successive determinations of HHb, HbO2 and HbCO. It was found that the method is applicable to old denatured blood when combined with the cyanmethemoglobin method. Methemoglobin (Met-Hb) in blood was also estimated by subtracting the sum of HHb, HbO2 and HbCO from total hemoglobin (total Hb.) Blood Met-Hb levels in six victims of city gas poisoning were practically negligible, while those in five victims of fire were 13.5-26.3%.


[Gynecologic tumors in childhood and adolescence].

These tumors, although rarely found, are of high clinical interest because of the difficulty of diagnosis and the problems of therapy. Symptoms which lead to the (provisional) diagnosis of tumors in female adults such as atypical bleeding, virilisation, growth of the abdominal circumference and the like are often ignored or not recognized in childhood. As a result, therapy often is started too late. More complications and greater difficulty of therapeutical measures such as operations, radiation and chemotherapy are encountered in childhood than in adult life. Frequency and morphology of gynecoligic tumors are described and diagnosis and therapy are discussed.


Techniques used in the evaluation of vertebral artery trauma at post-mortem.

Techniques for the examination of trauma to the vertebral arteries are described in detail. The importance of the preparatory dissection is emphasised, as well as the need for radiological, and detailed gross and microscopic examination. Reference is also made to the categories of cases in which this examination may be of particular value.


Morphine: its quantitative determination in nanogram amounts in small samples of whole blood by electron-capture gas chromatography.

A method for the determination of nanogram quantities of morphine in hemolyzed whole blood taken post mortem, or other blood samples of poor quality, has been developed. Morphine was extracted into ethyl acetate from blood at pH 8.7-9.0, and purified by absorption onto a column of acid aluminium oxide and elution with methanol. Nalorphine was added as an internal standard, the compounds derivatized with pentafluoropropionic acid anhydride, and the derivatives formed quantified by electron-capture gas chromatography. The recovery of morphine added to whole blood was 83%, the coefficient of variation 6.7%. The method is capable of measuring morphine concentrations of 1 ng/g in 0.1-0.2 g of post-mortem blood.


[Geriatric gynecology with special reference to malignant tumors].

After the enumeration of every single problem encountered in the geriatric gynecology, it has been proved, that the malignant tumors of such cases are of a special significance. according to the epidemiological facts of the Austrian Cancer-Registration-Statistics between the years 1971--1975 (even if the cancer of cervix uteri is excluded) more than 60% of the cases are still seen in the geriatric group. Increasing risk (by rate of incidence) of malignant tumors of internal genitals or the breast in aged women is also known and is proved to be very specific. Inspite of the progress won in geriatric surgical gynecology, the post-operative complications are still the negative factors, which limitate the success. Therefore today radiotherapy of the malignant tumors especially in geriatric-gynecological patients is gaining more and more importance.


[Experiences with an antimycotic tampon in the treatment of saccharomycetic vaginal infection].

Antimycotic (miconazole) medicated tampons were used for treatment in 53 patients with vaginal saccharomycetic infections as evidenced by hanging drop and on culture. A short term 2 1/2 day treatment with 5 tampons showed a success rate of 92.5%. The fast relief of symptoms like discharge, itching and burning is an improvement of the medicated tampon treatment. The new medicated tampons are considered as improvement of local vaginal treatment.


Red cell PGM1 (phosphoglucomutase) phenotyping by isoelectric focussing and starch gel electrophoresis in cases of disputed paternity in the United Kingdom. An evaluation of the results obtained in 95 cases.

Using two techniques for red cell PGM1 (phosphoglucomutase) phenotyping, namely starch gel electrophoresis and isoelectric focussing, a parallel study has been carried out in 95 paternity cases. The results again confirm the genetic basis for the extended polymorphism revealed by isoelectric focussing. Fifteen men were excluded from paternity on the basis of isoelectric focussing compared with seven excluded by starch gel electrophoresis. This was found to be in good agreement with the predicted increase in exclusion rate that the isoelectric focussing technique for red cell PGM1 provides.


Glyoxalase I in studies of paternity cases in Poland.

The distribution of glyoxalase I (GLO) types in cases of disputed paternity is reported. On the basis of 553 paternity cases, it is concluded that the GLO system is a valuable supplement to other systems of genetic markers in cases of disputed paternity. The theoretical probability of paternity exclusion in the GLO system, in the Polish population, is 18.6%.


[Utilization of Raoul Hoffman's Fixateur externe: indications and results].

In the Berufsgenossenschaftliche Unfallklinik Murnau (a Workmen's Association Emergency Hospital) 101 patients were treated with the Raoul Hoffmann-Fixateur externe. In patients with fresh bone fractures this system was very useful in cases with large soft tissue damages, with compound fractures and when the fractures were located very close to a joint. Good results were achieved also in the treatment of patients with pelvic fractures by using the Raoul Hoffmann-apparatus. In cases of old fractures no osteomyelitis occurred after introducing the nails and bone-screws of the Fixateur externe. Even with the Raoul Hoffmann-apparatus still in the bone physical therapy and the general care of the patient was easily possible. According to our experiences the Fixateur externe proved to be a valuable aid in traumatology besides the usage of plates and medullary nails.


The erythrocyte acid phosphatase isoenzyme distribution among the negroid population of Rhodesia.

The value of the erythrocyte acid phosphatase isoenzyme system as a method for blood typing in forensic science in Rhodesia has been evaluated. Three hundred and three blood samples from negroid people were examined. The high incidence of the B phenotype (72%) results in a poor division of the population using this system. The R allele which has been found in other negroid peoples also occurs in the Rhodesian population.


[Ligament ruptures of the upper ankle joint: diagnosis and therapy].

Supination-stress at the upper ankle often is reason for ruptures of capsula and ligaments. Surgical repair shows better results than conservative treatment. Diagnosis and therapy of 125 ruptures of the fibular ligaments and capsulae are reported.


[Treatment of progressive chronic polyarthritis with a non-steroidal antirheumatic agent with a long half-life].

73 patients with definite active rheumatoid arthritis were treated with naproxen, 250 mg b.i.d. One month after the start of therapy the patients were examined as to following parameters: spontaneous pain and pain on movement, duration of morning stiffness, fatigue, grip strength, functional joint index, ESR and consumption of analgesics. On statistical analysis a significant improvement of all the parameters, with the exception of ESR was shown, 52 of the 73 patients were very satisfied resp. satisfied with the treatment, whereas the physician evaluated the therapeutic results as very good to good in 49 of the cases. In 50 of the patients the therapy with naproxen, 250 mg b.i.d., was continued for two more months. In most of these cases it was possible to achieve an additional improvement in the parameters evaluated. Unwanted side effects occurred in 7 patients, of which in 4 the treatment had to be discontinued (in two cases because of dyspepsia and once each because of an angioneurotic edema and a recurrence of a peptic ulcer, respectively). The three patients in whose cases therapy was continued suffered from mild gastrointestinal disturbances.


[Intestinal gas gangrene originating from the gallbladder: diagnosis, therapy, report of 2 cases].

The problems of diagnosis and therapy of gas gangrene of the gastrointestinal tube and the gallbladder are discussed. 2 cases of gas edema of the gallbladder due to clostridium perfringens are reported. One of the patients survived. The early diagnosis of gas gangrene is important because of the extraordinary way of infection and the necessary early surgical and medicamentous therapy.


[Bronchial cancer: diagnosis, therapy and results].

A review of 603 cases of carcinoma of the bronchi is given. Symptoms, diagnosis and therapy are discussed. The five year survival-rate is 22%. The problem of early diagnosis is pointed out.


[Intrapulmonary teratoma: case report and review of the literature].

A case of a malignant intrapulmonary teratoma is described. 21 other cases published in the literature are reviewed. The third pharyngeal pouch is suggested to be the origin of these teratomata.


Nomenclature of the univentricular heart.

A simple system for the analysis and classification of the univentricular heart is described. The basis of this approach is the use of a step by step sequential nomenclature with attention paid to the morphology, connexions and relationships of each cardiac segment in turn. Three major morphological types of univentricular heart are identified and these may be distinguished, by their characteristic trabecular patterns, into hearts of left ventricular type, right ventricular type and indeterminate type. With the exception of the last it is usual for a rudimentary second chamber to be present upon the use of a clear definition of "ventricle", depending on readily ascertainable anatomical characteristics. Each morphological type of univentricular heart may be associated with a wide variety of different connexions and intracardiac relationships and it is neither possible nor desirable to describe these in terms of a rigidly structured classification. Adherence to the simple semantic framework outlined would resolve much of the confusion and controversy which exists in relation to the univentricular heart.


Morphology and conducting tissue in univentricular hearts of right ventricular type.

22 specimens of univentricular hearts of right ventricular type were examined morphologically. 6 hearts were sectioned for study of the conducting tissue. All the specimens had rudimentary second chambers, which were frequently so small as to have been overlooked, both angiographically and at initial morphological study. The segmental connexions and intracardiac relationships varied widely. Examples were found with 2 atrioventricular valves, a common valve and with absence of either the right or the left atrio-ventricular connexion. In some cases straddling of an atrioventricular valve was observed. The rudimentary chambers always lay posteriorly but varied between a position to the left of the ventricle and one to the right. The septum between ventricle and rudimentary chamber ran to the crux of the heart in all but 2 instances. In most specimens both great arteries arose from the ventricle (double outlet ventricle), so that the rudimentary chamber was solely a trabecular pouch. 4 hearts had concordant arterial connections with the aorta arising from a posterior "outlet" chamber. Pulmonary atresia was found in 5 cases and aortic atresia in 2. The conduction system originated from a normally placed atrioventricular node in 4 out of 6 cases and was related to the trabecular septum in 5. The penetrating bundle usually descended onto the crest of the septum at the "crux" of the heart and bifurcated astride it. In 2 cases with an absent atrioventricular connexion the penetrating bundle originated from an abnormally placed node and in one of these specimens a sling of conducting tissue was identified with dual pathways.


Univentricular hearts: pathology of the atrioventricular valves.

Anomalies of the atrio-ventricular valves are frequent in cases of univentricular heart with severe symptomatology during the first year of life and in necropsy material. This suggests that they are important determinants of the natural history of the malformation. Radical "corrective" surgery, in the presence of these anomalies, may be less successful than palliative programs based on sound physiological grounds. Under such circumstances, enlargement or creation of an atrial septal defect may be necessary. A careful assessment of the state of the atrio-ventricular orifices has to be included in the cardiac catheterization protocol of cases of univentricular hearts. From a morphogenetic viewpoint, a single ventricular cavity is not the appropriate substrate for two normal atrio-ventricular valves to develop.


Atrioventricular conduction tissues in univentricular hearts of left ventricular type.

Univentricular heart of left ventricular type is defined as the condition in which the entirety of atrial inputs is committed to a main chamber exhibiting trabecular pattern of left ventricular type, usually in the presence of another chamber in the ventricular mass which has a right ventricular trabecular pattern. This condition can occur with two atrioventricular valves, a common atrioventricular valve, a straddling atrioventricular valve or with absence of the right or left atrioventricular connexions. The hallmark of univentricular heart of left ventricular type is absence of the inlet septum, which normally separates the inlet portions of the two ventricles and which in the normal heart carries the atrioventricular conduction bundle. In univentricular heart of the left ventricular type, as a consequence of its absence, an abnormal disposition of the atrioventricular conduction tissues is found. An anterior or lateral atrioventricular node is present from which the prenetrating bundle descends onto the trabecular septum separating main chamber from rudimentray chamber. The topographical relationship of the bundle particularly with respect to the outflow tract of the posterior great artery from the main chamber, depends on the position of the rudimentary chamber. In atrial situs solitus, a left-sided rudimentary chamber will be associated with a long bundle in close proximity to the ostium of the posterior great artery from the main chamber. In contrast, in the heart with a right-sided rudimentary chamber the bundle will stay remote from the posterior outflow tract. The position of the rudimentary chamber will also alter the site of the ventriculotomy for any proposed corrective surgery and, hence,, alter the relationship of the bundle relative to the outlet foremen, as viewed by the surgeon. The general disposition of the atrioventricular conduction system in univentricular heart of left ventricular type is not altered by the type or mode of the atrioventricular connexion, nor by the type of the arterial connexion.


The relationship between single ventricle and small outlet chamber and straddling and displaced tricuspid orifice and valve.

This paper deals with the anatomic differences between single ventricle and small outlet chamber, straddling tricuspid orifice and valve, and displaced tricuspid orifice and valve. In single ventricle, both atrioventricular orifices enter a chamber which contains the sinuses of both definitive ventricles, while a small outlet chamber represents the definitive infundibulum of the right ventricle. In straddling tricuspid orifice and valve, the primitive left ventricle contains the sinus of the definitive infundibulum of the right ventricle. In straddling tricuspid orifice and valve, the primitive left ventricle contains the sinus of the definitive left ventricle and also a portion of the sinus of the definitive right ventricle. The primitive right ventricle contains the infundibulum and part of the sinus of the definitive right ventricle. In displaced tricuspid orifice, the primitive left ventricle contains the sinus of the definitive left and almost all of the sinus of the definitive right ventricle. However, a posterior ventricular septum is formed, so that a portion of sinus or apical recess of the definitive right ventricle is included in the primitive right ventricle together with its infundibulum. Possible embryologic speculations are offered to account for these entities. The differences in the anatomy of these entities may be important to the surgeon.