Preferential incorporation of some 14C-labeled D-amino acids into tumor-bearing animals. In order to acquire a fundamental knowledge for the development of better tumor-scanning agents, the in vivo incorporation pattern of three 14C-labeled D-amino acids, alanine, leucine, and tryptophan, into the tumor cells and organs of animals bearing Ehrlich mouse tumor, sarcoma-180, leukemia L-1210, or Yoshida sarcoma was investigated, and compared with that of the corresponding L-forms. The radioactivity of D-amino acids tested was most highly found in tumor cells and pancreas, and the activity in tumor cells was several times higher than that of L-forms. A large portion of the radioactivity of D-forms was found in trichloroacetic acid-soluble fraction of the cells, whereas that of L-forms was mostly in protein fraction, except L-alanine. Although the mechanisms whereby the radioactivity of D-amino acids was concentrated more than that of L-forms in the tumor cells have not yet been clearly elucidated, it was concluded that gamma-emitter-labeled D-amino acids themselves or their derivatives might be useful as tumor-detecting radiopharmaceuticals.


Antitumor activity of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride in a variety of experimental tumors. A water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU, NSC-245382), was tested for its antitumor activity against some kinds of transplantable mouse tumors. The compound was markedly active against myeloid leukemia C1498, plasmacytoma X5563, Ehrlich ascites carcinoma, and mammary tumor FM3A43, and moderately active against mammary tumor MM102 and meningeal sarcoma MS147. It appears that ACNU has a broad antitumor spectrum.


Mechanism of natural resistance of rat ascites hepatomas to 1-beta-D-arabinofuranosylcytosine. The biochemical basis for natural resistance to 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in the intact cells of 4 rat ascites hepatomas, AH-66F, AH-60C, AH-109A, and AH-66, whose sensitivity to ara-C was different in that decreasing order. The initial rapid uptake of ara-C, mediated by the facilitated diffusion, was similar in all the cell lines tested but the subsequent slow uptake due to phosphorylation of ara-C was inversely correlated with their drug resistance. The capacity for drug phosphorylation was slightly higher in AH-66F and much lower in AH-60C, AH-109A, and AH-66 than in the host bone marrow. In contrast, mouse leukemia L-1210, one of the tumors sensitive to ara-C, phosphorylated the drug about 7 times faster than AH-66F and 4 times faster than the host bone marrow. More than 95% of phosphorylated ara-C was the triphosphate, the active form. Deamination of ara-C was not observed in any tumor or bone marrow. It is concluded that the low capacity for nucleotide formation is related to the natural resistance of rat ascites hepatomas to ara-C.


Effect of dose on the carcinogenic activity of orally administered N-bis(2-hydroxypropyl)nitrosamine in rats. The carcinogenic activity of orally administered N-bis(2-hydroxypropyl)-nitrosamine (DHPN) in male Wistar rats was evaluated with respect to its dose. DHPN was administered at two doses, 100 ppm and 500 ppm, in the drinking water to rats for 25 to 52 weeks. Tumors developed in the lung, liver, and thyroid of rats receiving 100 ppm DHPN and in the lung, liver thyroid, esophagus, kidney, and urinary bladder of rats receiving 500 ppm DHPN. The principal target organ was the lung in rats receiving either 100 or 500 ppm DHPN, indicating that the carcinogenic action of these doses of DHPN was similar to that of higher doses previously reported. Histologically, the tumors were adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma of the lung, hepatocellular carcinoma and hemangioma of the liver, adenoma and adenocarcinoma of the thyroid, squamous cell papilloma and carcinoma of the esophagus, renal cell and transitional carcinoma of the kidney, and transitional cell carcinoma of the urinary bladder. No pancreatic tumors were observed.


Distribution of 3-hydroxyanthranilic acid in mice. Distribution of 3-hydroxyanthranilic acid, a tryptophan metabolite suspected of being carcinogenic, was studied in mice. After sc injection of 3-hydroxyanthranilic acid generally labeled with tritium into male (BALB/c X DBA/2)F1 mice, the distribution of tritium was investigated by whole-body autoradiography and radioactivity measurement. Then, metabolites in the organs and urine was analyzed by paper and thin-layer chromatography. At 30 and 60 min after injection, tritium was distributed mainly in the liver and kidneys, and after 6 hr, tritium remained in the lymphoid organs. However, at 30 min and 6 hr after injection, 3-hydroxyanthranilic acid and its metabolites that might be related to carcinogenic action could not be detected in the liver, kidneys, spleen, or lymph node. 3-Hydroxyanthranilic acid and its sulfate were detected only in urine. These results suggest that 3-hydroxyanthranilic acid is rapidly metabolized and does not accumulate per se in the specific organ. However, urinary organs can be exposed to this compound.


Frequency of anti-AG-4 antibody in patients with uterine cervical cancer and controls. Association of herpesvirus type-2 (HSV-2) with cervical cancer was studied from seroepidemiological viewpoint, using early antigen induced in Hep-2 cells by HSV-2 4 hr after infection (AG-4). The AG-4 antibody was assayed by the microquantitative complement fixation method. Antibody to AG-4 was respectively detected in 47% and 14% of cervical cancer patients and controls (P less than 0.001). There was a tendency of the antibody prevalence to increase with clinical stage. There was no correlation between prevalence of AG-4 antibody and that of HSV-2 neutralizing antibody estimated by the kinetics of neutralization assay, confirming previous conclusions that AG-4 differs from viral antigens involved in neutralization. Although previous study could not confirm higher prevalence of neutralizing antibody to HSV-2 in cancer patients, the present data suggest that HSV-2 is not unrelated to cervical cancer.


Bioassay of cholecystokinin in the duodenal mucosa. Cholecystokinin (CCK)-like activities in the duodenal mucosa were measured by bioassay in patients with duodenal ulcer, cholelithiasis and some other gastrointestinal diseases as well as in healthy normal subjects. The mean CCK-like activity of the duodenal mucosa in patients with duodenal ulcer and cholelithiasis was 0.405 Ivy dog units per milligram and 0.376 Ivy dog units per milligram of dry weight of the duodenal mucosa (IDU/mg d.w.), respectively. Both these figures are significantly higher than 0.180 IDU/mg d.w. in normal subjects (p less than 0.005, p less than 0.005, respectively). It can be speculated that the CCK-level of the duodenal mucosa in patients with cholelithiasis may be regulated by a feedback mechanism and CCK in patients with duodenal ulcer may act physiologically for the cure of duodenal ulcer.


Evaluation of fibergastroscopic biopsy in the diagnosis of gastric cancer: a study of 339 cases. Three hundred and sixty-five biopsies under direct vision, using a fibergastroscope, were performed on 339 patients with gastric cancer from 1966 to 1975. Diagnostic accuracy improved with an increased in the number of biopsy specimens and reached 100% when 6 or more biopsy specimens were obtained. Positive specimens were obtained with 48.5% of the biopsied tissue from the center of the lesion (A), 52.2% from the inner margin of the lesion (B1), 19.6% from the outer margin of the lesion (B2), and 1.6% from the area around the lesion (C). The combined result of the biopsies from A and B1 was highly positive in 49 out of 51 cases (96.1%). Diagnostic accuracy of the early cancer reached 96.9%. This was significantly higher than that of advanced cancer (80.3%). False negative biopsies were found in 51 (16.3%) of the 313 patients who were gastrectomized and diagnosed by histological examinations. Twenty-three of the 27 patients, who were diagnosed as benign either by x-ray or endoscopic examination, and 4 of the 5 patients who were diagnosed as benign under both examinations, were found to have positive results by biopsy. Positive biopsy examination was particularly helpful with patients showing on inconclusive or benign diagnosis by x-ray and/or endoscopic examinations.


Clinicopathological study of gastric leiomyogenic tumors. 1. Seventy cases of the leiomyogenic tumors were found in 5451 resected stomachs; 49 leiomyoma, 17 leiomyosarcoma and 4 leiomyoblastoma. These leiomyogenic tumors occupied 40.5% of 173 submucosal tumors of the stomach. 2. The average age was 51.7 in leiomyoma, 57.3 in leiomyosarcoma and 41.6 in leiomyoblastoma with male predominance. 3. The leiomyoma and leimyosarcoma were frequently found in the upper 2/3 of the stomach. 4. The size of the tumors was within 3 cm in diameter in about 80% of leiomyoma with ulcer formation of 10.2% and over 3 cm in about 88% of leiomyosarcoma with ulcer formation of 64.7%. 5. The classification of the leiomyogenic tumors into the benign and malignant was occationally difficult. For the diagnosis of the leiomyosarcoma, the number of mitosis, irregularity of nucleus, increase of cellularity and decrease of smooth muscle production were helpful.


Recurrent common duct stones, with special reference to primary common duct stones. A series of 1,358 cholelithic patients operated on at 32 affiliated hospitals during the last year and 492 patients operated on at authors' hospital during the last 21 years were reviewed with special reference to the cases of recurrent common duct stones. Of the former series 15 patients and of the latter series 12 patients respectively were reoperated on for recurrent, but not for residual, common duct stones, and all of them had in the markedly dilated common duct bilirubin stones showing characteristics of stasis stone-primary in common duct. Two representative cases are presented briefly. Congenital hypotonia of the common duct and inflammatory choledochitis are condemned and bilioenterostomy is recommended for preventing stone recurrences.


A case of Menetrier's disease associated with protein-losing gastropathy and abnormal serum complement profile. A 44-year-old man with Menetrier's disease associated with protein-losing gastropathy and with abnormal serum complement profile is reported. He was treated by an antifibrinolytic compound tranexamic acid (trans-AMCHA) since he was found to have elevated fibrinolytic activity in the biopsied gastric mucosa. The therapy brought his serum protein from 3.8 g/dl to 5.6g/dl, however could not reduce his mucosal disorder. Substitution of a placebo for trans-AMCHA resulted in marked depression of his serum protein to 3.7 g/dl. It was concluded that trans-AMCHA was effective in raising his serum protein to a certain extent but failed to block the vicious circle of "mucosal disorder", "increased tissue fibrinolysis" and "hypoproteinemia" (Kondo, M. et al. Gastroenterology 70, 1045, 1976). Abnormal serum complement profile seen in this patient was found to be due to cold activation of the classical complement pathway (Kondo, M. et al. J. Immunol. 117, 486, 1976). Although no correlation between the phenomenon and Menetrier's disease has been clarified yet, the appearance of wheezing as in asthma when exposed to cold suggested that cold activation of complement occurred in vivo and resulted in increasing of the vascular permeability in the lungs.


Plasma alpha-amino-n-butyric acid to leucine ratio: nonspecificity as a marker for alcoholism. Recent studies suggest that the ratio of plasma alpha-amino-n-butyric acid to leucine is increased specifically by chronic heavy alcohol consumption. To test this hypothesis, we determined this ratio in normal controls and (1) currently drinking chronic heavy alcoholics; (2) currently abstaining chronic alcoholics; (3) patients with nonalcoholic liver disease; (4) chronically alcohol-fed rats and mice; (5) mice infected with murine hepatitis virus; and (6) mice exposed to carbon tetrachloride. Mean ratios in control persons, drinking alcoholics, abstaining alcoholics, and nonalcoholic liver disease patients were not statistically different. Of 5 drinking alcoholics followed serially from the beginning of abstinence, 1 had an elevated ratio on admission and a persistently elevated ratio even 2 weeks later; another had a ratio more elevated after 2 weeks of abstinence, than on admission; and 3 had ratios in the normal elevated after 2 weeks of abstinence than on admission; and 3 had ratios in the normal range. Compared to control rats, chronically alcohol-fed rats had a significantly elevated mean ratio after 1 month and an even higher ratio after 2 months (P less than 0.001). In control, alcohol-fed and carbon tetrachloride-treated mice, alpha-amino-n-butyric acid was undetectable, but in two sets of mice with severe murine hepatitis virus infection, elevated ratios were found. We conclude that because the ratio of alpha-amino-n-butyric acid to leucine is not necessarily elevated in chronic heavy alcoholics but can be elevated in acute experimental liver cell injury, it does not appear to be a specific marker for the detection of alcoholism.


Drug metabolism in liver disease. Identification of patients with impaired hepatic drug metabolism. Antipyrine half-life (AP t1/2) was measured in 62 patients with, and 10 control patients without, liver disease to ascertain possible factors which may be useful in identifying patients with abnormal drug metabolism. Antipyrine metabolism was normal or marginally impaired in patients with compensated cirrhosis or acute hepatitis, whereas it was frequently abnormal in those with chronic active hepatitis or advanced alcoholic liver disease. A high degree of correlation was found among AP t1/2 and prothrombin time, hepatic encephalopathy, and ascites. Of patients  with severely impaired drug metabolism, 80% had one or more of these features. The severity of histological changes in liver biopsies was of additional help in predicting impaired drug metabolism. Concurrent drug ingestion enhanced antipyrine metabolism in most patients with liver disease as well as in control patients. Inadequate diet was associated with prolongation of AP t1/2, but other environmental factors such as alcohol ingestion, cigarette smoking, and coffee consumption did not affect rates of drug metabolism in patients with liver disease. Consideration of all of the above factors allows qualitative predictions of the rate of hepatic drug metabolism in patients with liver disease, as assessed by the AP t1/2.


Radioimmunoassay of plasma ligandin: a sensitive index of experimental hepatocellular necrosis. The development of sensitive and specific radioimmunoassay for ligandin, a protein present in abundance in the hepatic cytoplasm, has permitted measurement of ligandin in rat plasma. Plasma ligandin levels were estimated in normal, carbon tetrachloride (CCl4)-treated, and bile duct-ligated rats, with parallel estimation of serum glutamic oxaloacetic transaminase (SGOT). Plasma ligandin levels rose at a greater rate and to higher levels than did SGOT in CCl4-treated rats and showed a more linear increment to increasing doses of CCl4. A marked depletion of hepatic, but not renal ligandin, was associated with CCl4 poisoning. Twelve hours after acute bile duct ligation, both plasma ligandin and SGOT were moderately elevated, plasma ligandin returning to normal by 24 hr, at which time SGOT was still raised. The findings of this study indicate that plasma ligandin is a sensitive index of experimental hepatocellular necrosis.


Bilary lipids and bile acid pool size after vagotomy in man. Evidence against a predisposition to gallstones. Eight male subjects who had previously undergone vagotomy and pyloroplasty were found to have significantly larger bile acid pools than did a group of matched control subjects. Associated with these expanded pools was a significantly lower molar per cent cholesterol of gallbladder bile in the vagotomy group. These findings are the opposite of those expected in a group predisposed to cholesterol cholelithiasis, suggesting that vagotomy, at least in males, does not predispose to cholesterol gallstones. If such stones form after vagotomy, they presumably do so by a mechanism not presently appreciated.


Some parameters of large bowel motility in normal man. This study presents normal values of bowel habits, colonic transit times of radioopaque markers, and anorectal pressure obtained from 114 normal subjects. Their stool frequency ranged from 3 to 11 per 7 days, whereas their diet contained an average of 14.4 g of crude fibers. Radioopaque markers progressed regularly along the large bowel and a range of transit times was established for its different segments. Manometric studies included measurements of anal pressure at rest, amplitude and duration of the rectoanal inhibitory reflex, anal inflation reflex, and amplitude of rectal contraction in response to rectal distension. Normal ranges were established. Amplitude, duration and magnitude (as measured by planimetry) of anal relaxation elicited by rectal distensions were related to rectal distending volume (P less than 0.001). The incidence of spontaneous variations of anal pressure at rest and of overshoot of pressure after the inhibitory reflex was also established. These data obtained on normal subjects may be compared to those obtained in patients with constipation in order to define the symptoms and to understand pathophysiological mechanisms. This has been done in a companion study.


Barium enema in chronic constipation: is it meaningful? Seventeen pairs of pre- and postoperative barium enemas performed under fixed conditions (same preparation, filling technique, and radiographic factors) were selected from the records of a group of 62 chronically constipated patients who had undergone anorectal myectomy. Measurements at different levels of the large bowel and over-all subjective diagnosis were compared to those made in group of 26 controls. The barium enema did not aid in the diagnosis of constipation or its evolution after surgery.


Mechanisms of idiopathic constipation: outlet obstruction. Anorectal myectomy was performed in 62 patients suffering from symptoms attributed to ineffective colonic motility. Indications for surgery rested on the presence of one or more of the following three criteria: abnormally reduced stool frequency, prolonged transit of radioopaque markers, and abnormal anorectal manometry. One year after myectomy in the 50 patients with less than three stools per week the average number of stools per week increased from 1.2 to 4.2 (P less than 0.001). The remaining 12 patients, who had more than three stools per week, were completely relieved of their symptoms. In all cases with improved symptoms, myectomy acclerated the transit of radioopaque markers through the large bowel. Organic constipation amenable to surgical treatment is more frequent than previously thought. Idiopathic constipation may result from colonic inertia or outlet (anorectal) obstruction.


Predisposition to gastric erosions in the rat: behavioral and nutritional effects of early maternal separation. After early maternal deprivation (on postnatal day 15), the incidence of restraint-induced gastric erosions on day 30 increases to approximately 5 times that of rats separated at the customary (day 21) weaning age. These data suggest that factors in the mother-infant relationship during postnatal development in young rats can influence later susceptibility or resistance to gastric erosions. We present a series of experiments to test whether loss of behavioral interaction with the mother or loss of maternal milk results in this increase in gastric erosion susceptibility. The results show that the absence of maternal milk, rather than behavioral deprivation, is primarily responsible for the increase in susceptibility after early maternal separation. However, behavioral interaction with the mother can additionally modify this susceptibility.


Effects of compounds chemically related to salicylate on isolated antral mucosa of rabbits. This study examines some of the gastric mucosal effects of compounds structurally related to salicylate (which consists of a hydroxyl and a carboxyl group attached to a benzene ring) in order to determine the importance of the various ligands of the salicylate molecule. The presence of carboxyl group increases mucosal permeability to acid. This increase in cation flow initially is associated with a decrease in anion permeability. These ion selective effects subsequently give way to a nonspecific increase in permeability. The presence of a carboxyl group also is associated with a more than 80% decrease in short circuit current. A similar decrease in short circuit current occurs when the mucosa is exposed to a pyridine molecule with an attached carboxyl group (pyridine-3-carboxylic acid), but in a relatively low concentration, this agent also decreases the back diffusion of acid. The above noted changes in mucosal permeability and short circuit current do not appear to be attributable to the benzene or phenolic ligands of the salicylate molecule. It is concluded that the presence of a sufficient concentration of an exposed carboxyl group on the mucosal side of the tissue causes an increase in the permeability of the mucosa to acid. The presence of a carboxyl group also appears to alter active ion transport, but this effect cannot be attributed to enhanced diffusion of acid into the tissue. The data implicate the carboxyl group of salicylate as being key to its damaging effects on the stomach.


Effect of propranolol on ricinoleic acid- and deoxycholic acid-induced changes of intestinal electrolyte movement and mucosal permeability. Evidence against the importance of altered permeability in the production of fluid and electrolyte accumulation. Hydroxy fatty acids and bile acids produce both intestinal fluid and electrolyte accumulation and increases in inulin clearance, a parameter of mucosal permeability. The relationship of the changes in mucosal permeability to the production of fluid and electrolyte accumulation is uncertain. These experiments were designed to determine whether the alterations of mucosal permeability produced by ricinoleic acid and deoxycholic acid were related to production of hydroxy fatty acid- and bile acid-induced fluid and electrolyte accumulation in the rat colon. Propranolol (1 mg per 100 g of body weight) administered daily for 3 days inhibited ricinoleic acid- and deoxycholic acid-induced Na and water accumulation. In contrast, propranolol did not affect either the increase in inulin clearance or the decrease in electrical potential difference produced by ricinoleic acid and deoxycholic acid. Further, amphotericin B increased inulin clearance by the colon and also increased water and Na absorption. These studies suggest that changes in mucosal permeability are not primarily responsible for hydroxy fatty acid- and bile acid-induced fluid and Na accumulation.


Cell proliferation in esophageal columnar epithelium (Barrett's esophagus). In order to correlate histopathology and cell turnover in esophageal tissue in patients with esophageal columnar epithelium, biopsy specimens from 11 patients were studied. Two of the patients had adenocarcinoma of the esophagus not present in the specimens studied. In the heterogeneous esophageal columnar epithelium, the DNA synthesis phase averaged 10.4 +/- 0.3 hr; labeling index of cells in the crypt-like structures was 23.3 +/- 0.3%; generation time was 44.6 +/- 1.2 hr, and the mitotic index was 1.82 +/- 0.07%. Significant differences were not present among specimens with columnar epithelium but they differed from cell proliferation in adjacent squamous epithelium where S phase was similar but labeling and mitotic indexes were lower and generation time increased to 105 +/- 6 hr. In the 2 patients with adenocarcinoma of the esophagus, and in 1 of 9 without adenocarcinoma, labeling of surface columnar cells after brief exposure to [3H]thymidine was present suggests that this may be a manifestation of early malignant change.


Iron transport by isolated rat intestinal mucosal cells. In vitro uptake of radioiron by suspensions of isolated rat duodenal mucosal cells has been examined. The cells bind iron avidly, with uptakes of 15 to 20% after 20 min of incubation. Uptake is dependent upon temperature, pH, and iron and cell concentration. It is unaffected by inhibitors of cellular respiration but is blocked in a concentration-dependent fashion by iron-chelating agents. Iron-deficient cells take up iron at the same rate as normal cells. Binding by brush borders appears to account for 50 to 60% of the total uptake by isolated cells. In vitro radioiron uptake by isolated cells occurs by passive diffusion, is not regulated by the animal's iron status, and is primarily a function of bioavailability of iron in the incubating medium. If the model reflects the behavior of cells in vivo, the initial uptake of iron by the mucosa is a passive process which may serve to concentrate dilute luminal iron at the mucosal surface in preparation for absorption.


Definitive diagnosis of gluten-sensitive enteropathy. Use of an in vitro organ culture model. The flat mucosal lesion of the small intestine is not pathognomonic of gluten-sensitive enteropathy (GSE). Frequently, the definitive diagnosis of this condition can only be established after three intestinal biopsies are performed: an initial one to show a flat mucosal lesion, one after a gluten-free diet to show morphological recovery, and one after a gluten challenge to show morphological deterioration. We used an organ culture model of GSE to determine the usefulness of this technique in establishing a diagnosis of GSE on the basis of the initial biopsy. Seventy-five patients with diarrhea, and/or malabsorption were evaluated prospectively; 40 had a flat mucosal lesion of variable degree; of these 26 were ultimately determined to have gluten-sensitive enteropathy by the above criteria. A rise in alkaline phosphatase activity of intestinal tissue from 22 of these 26 patients was inhibited when the tissue was cultured in gluten-containing medium as compared to enzyme activities of cultures in a gluten-free medium (108 +/- 69 versus 206 +/- 96, mean +/- SD, P less than 0.001). Mean enzyme values in the similarly cultured intestinal tissue from 13 of 14 patients ultimately shown not to have GSE were not affected by gluten (224 +/- 94 versus 201 +/- 109, P greater than 0.4). Examination of the data by stepwise discriminant analysis provided a function which correctly classified 35 of the 40 patients (88%). The false-positive and false-negative rate for establishing the diagnosis of GSE was 7% (1 of 14) and 15% (4 of 26), respectively. All patients with normal biopsies were classified correctly. The model can be used to establish prospectively the definitive diagnosis of GSE, obviate the need for additional diagnostic biopsies, and allow for the prompt pursuit of alternative diagnoses when gluten sensitivity is not shown.


Rectal mucosa in cystic fibrosis. Morphological features before and after short term organ culture. Histological changes observed in the large intestinal mucosa of cystic fibrosis (CF) patients, including crypt enlargement as well as intracellular and extracellular accumulation of mucus, have been considered by some to be useful diagnostic signs of this disease. The extent of these changes, however, has not been evaluated quantitatively. In this study, quantitative stereological methods were applied to biopsies of rectal mucosa from 5 CF patients, 5 sibling controls, and 2 normal adults, to measure goblet cell numbers, crypt luminal volume, and volume of intracellular mucus. It was found that CF crypt lumina were variably dilated, but that the average relative volume of intracellular mucus and the numbers of goblet cells in CF mucosae were comparable to those of sibling and adult controls. In CF biopsies, however, surface columnar absorptive cells consistently contained putative lipid droplets and rapidly accumulated additional large lipid droplets during short term organ culture. Lipid droplets were not observed in the same cell types of control biopsies before or after short term organ culture.


Small intestinal epithelial renewal in the Syrian hamster exposed to cholera enterotoxin. Epithelial renewal of the small intestine was measured in the Syrian hamster utilizing tritiated thymidine by standard autoradiographic and a scintillation counting technique. Scintillation counting of intestinal replicates proved to be as accurate as standard autoradiography. Average mucosal cell turnover was 71 +/- 3.0 hr in jejunum and 79 +/- 4.2 hr in ileum. Scintillation counting was utilized to study the effect of a maximum cholera enterotoxic secretory stimulus on small intestinal mucosal cell turnover. No significant change in epithelial cell migration occurred during cholera enterotoxin (CT)-induced fluid and electrolyte secretion. The rate of decline in radioactivity as a measure of cell turnover in CT-exposed animals was no different from controls. Epithelial cell proliferation 1 to 42 hr after CT exposure showed no difference from controls. Intestinal fluid and electrolyte secretion persisted for 24 hr after CT exposure. It is concluded that (1) the small intestinal epithelial cell migration was unaltered by this metabolic secretory stimulus, and (2) the data are consistent with the concept that epithelial migration after CT exposure was one factor, although not necessarily the major determinant of the progressive decline in intestinal secretory activity.


Jejunal biopsy with the Watson capsule and perforation in the elderly. Details of jejunal biopsies using the Watson small intestinal biopsy capsule done from 1966 through 1976 at three centers in Liverpool were obtained. The only complications were jejunal perforation which occurred in 2 patients over 65 years of age, 1 of whom died. This increased risk in elderly does not appear to have been previously recognized and both cases are reported. Diagnostic yield in the age group over 65 is discussed. Stricter criteria in selection of these patients for biopsy are suggested. A period of in-patient observation after biopsy in those over the age of 65 may decrease the risks of perforation. In addition, the use of a pediatric capsule, ideally with controlled suction, may lessen the risk further. The use of duodenal biopsy via an endoscope may prove to be a useful additional technique in elderly patients.


Sex differences in hepatic sulfation of taurolithocholate in the rat. Metabolism of the bile salts by formation of sulfate esters is catalyzed by bile salt sulfotransferase, an enzyme isolated from rat liver and kidney. The activity of bile salt sulfotransferase was measured in liver and kidney of male and female rats and in oophorectomized rats with or without estrogen replacement. In vitro sulfotransferase activity was correlated with in vivo sulfation by measuring the percentage of an infused dose (0.03 micron per 100 g per min) of taurolithocholate, which was excreted in bile as the sulfate. The activity of sulfotransferase in liver was higher in females (26.3 +/- 3.0 pmoles per mg of protein per min) than in males (9.6 +/- 3.9) and was lower (12.1 +/- 3.8) after oophorectomy. The decrease in activity was prevented by replacement of estrogen. Renal sulfotransferase activity did not differ between the sexes and was unaffected by oophorectomy. Hepatic sulfotransferase activity measured in vitro correlated with in vivo sulfation of taurolithocholate. This study shows definite sex differences in hepatic bile salt sulfotransferase activity, which in females is affected by the presence of estrogen. The correlation between in vitro sulfotransferase activity and in vivo bile salt sulfation suggests that bile salt sulfotransferase is responsible for bile salt sulfation in vivo.


Decarboxylation to tyramine: an important route of tyrosine metabolism in dogs with experimental hepatic encephalopathy. Tyrosine metabolism via decarboxylation to tyramine was evaluated in dogs with functional end-to-side portacaval shunt. It was found that the endogenous plasma levels of both tyrosine and tyramine increased steadily after the construction of the shunt. These elevations became more pronounced when the dogs manifested symptoms of hepatic encephalopathy. In encephalopathic dogs, average endogenous plasma tyrosine and tyramine concentrations were 110.1 mumoles per liter and 7.6 ng per ml as compared to 55.4 and 1.2 in control dogs, respectively. The pattern of plasma concentrations of tyrosine and tyramine after an oral dose of L-tyrosine (50 mg per kg) was also investigated in control and shunted dogs. There was a progressive rise in peak levels of tyramine (to about 50-fold increase, at 6 weeks) after the construction of the shunt, as compared to levels obtained in pre- and at 1 and 4 weeks postoperatively (70.6 versus 1.20, 3.9, and 8.11 ng per ml). Similar observations were made with levels of plasma tyrosine. Six weeks after portacaval shunt, mean peak levels of plasma tyrosine, achieved at 5 hr after dose administration, were 450 as compared to 85 mumoles per liter obtained in preshunted dogs. These studies demonstrated a correlation between abnormalities in tyrosine metabolism and postshunt hepatic encephalopathy.


Significance of microscopic cholangitis in alcoholic liver disease. Marked biochemical cholestasis mimicking extrahepatic obstruction may occur in alcoholic liver disease. Twenty-three consecutive hyperbilirubinemic alcoholics who underwent liver biopsy were studied. Comparison of the clinical, laboratory, and histological features was made between patients with no or rare intraductal polymorphonuclear leukocytes, group A (19 cases), and those with polymorphonuclear leukocytes in multiple bile ducts ("microscopic cholangitis"), group B (4 cases). Extrahepatic biliary obstruction was excluded in group B by cholangiography. Group B had significantly higher serum SGOT, bilirubin, alkaline phosphatase, and cholesterol than group A. All group B patients had periductal acute inflammation and severe panlobular cholestasis. However, there was no significant histological difference comparing group A patients with alkaline phosphatase greater than 300 mIU per ml and group B patients, except for the presence of intraductal polymorphonuclear inflammation. Therefore, we conclude that microscopic cholangitis is a feature of severe cholestasis which may accompany alcoholic liver injury.


Experimental evidence for vasoactive intestinal peptide as the cause of the watery diarrhea syndrome. We have infused pure porcine vasoactive intestinal peptide (VIP) into 8 healthy ambulant unsedated pigs. At plasma VIP levels closely comparable to those found in the human Verner-Morrison syndrome, gross watery diarrhea and hypokalemia were produced. When the VIP infusion was discontinued the water diarrhea ceased abruptly. This study therefore provides some evidence to implicate VIP as a possible causal agent in the pathogenesis of the human watery diarrhea syndrome.


Survival in peptic ulcer.

Survival in peptic ulcer. The present study of the prognosis in peptic ulcer comprises (1) an analysis of deaths caused by the disease itself, and (2) an independent actuarial analysis of life expectancy. The computations are based on 235 deaths that occurred among 1905 patients with peptic ulcer who constituted a random sample of the occurrence of ulcer disease in an area of Denmark comprising half a million inhabitants. The two methods of analysis both showed that peptic ulcer does influence the survival, but the excess of deaths was small and, in the case of solitary peptic ulcer, was present only in the first year or two after the diagnosis. The prognosis tended to be more serious in gastric ulcer than in duodenal ulcer, but the difference was not significant. In duodenal ulcer the survival tended to be better when only a deformed bulb was present. The life expectancy was not significantly different for men and women. Patients with combined gastric and duodenal ulcers had a fatality twice as great as those with solitary ulcers. No excess of deaths was found in patients under the age of 50 years at diagnosis. The duration of prediagnostic symptoms was not predictive for the prognosis.


Alterations in cell surface membrane components of adapting rat small intestinal epithelium. Studies with lectins after massive proximal jejunoileal resection and jejunoileal transposition. After proximal resection or transposition of intestinal segments, the small intestinal mucosa of rats was examined with fluorescein-conjugated lectins derived from Ricinus communis and Triticum vulgare (wheat germ). These agglutinins are thought to be specific for the nonreducing end-terminal carbohydrate residues, beta-D-galactose and beta-N-acetyl-D-glucosamine, respectively. After 70% proximal jejunoilealal resection as well as transposition of ileal segments to jejunum, ileal villus cell surface labeling by both lectins was changed to a pattern characteristic of normal rat proximal intestine. Alterations were not detected proximal to the surgical anastomosis after massive resection or in the jejunal segments transposed to ileum. Although the labeling pattern of goblet cell mucin differed in proximal duodenum from the remainder of control small intestine in normal animals, no differences were detected in goblet cell mucin labeling between normal and resected or transposed animals. This study confirms the previously reported differential lectin-labeling patterns of the small intestinal crypt and villus cells and further emphasizes the differences between cell surface carbohydrate and secretory mucins of goblet cells. Furthermore, the changes induced in the cell surface-labeling pattern by massive proximal jejunoileal resection and transposition suggest that cell surface and secretory components may be altered differently during adaptation of the small intestine.


Binding of secretin to plastic surfaces. Five carboxyl-terminal fragments of secretin ranging in size from 6 to 21 amino acid residues were tested for pancreatic secretory activity in the rat. None of the fragments displayed activity when given alone but each displayed significant activity when given after secretin. This apparent activity was shown to be the result of displacement of secretin bound to the walls of the injection catheter. The activity was abolished by dissolving secretin in 2% bovine serum albumin. The finding emphasizes the ease with which secretin can bind to plastic surfaces and consequently the need to reevaluate previous dose-response studies and the caution required in the design of future studies.


Profiles of pure pancreatic secretions in patients with acute pancreatitis: the possible role of proteolytic enzymes in pathogenesis. Studies have been performed on pure pancreatic juice obtained by direct cannulation of the pancreatic duct in 2 patients with acute pancreatitis. The striking abnormalities observed, which were in marked contrast to our observations in 15 normal subjects, were high concentrations of protein throughout the period of secretin stimulation and the sporadic appearance of free proteolytic activity in many 1-min specimens throughout the collection period. In 1 subject repeat studies were performed after resolution of the pancreatitis when the profile observed was normal. Our findings are consistent with the hypothesis that obstruction of ductules and intraductal activation of zymogens may be important in the pathogenesis of acute pancreatitis.


Effect of acute hypercalcemia on human esophageal motility. In order to evaluate the effect of acute moderate hypercalcemia on both smooth and skeletal muscle function of the human esophagus, 12 subjects were given intravenous calcium chloride in normal saline. Serum calcium increased from a basal value of 9.6 +/- 0.1 mg per dl (mean +/- 1 SEM) to 11.4 +/- 0.2 mg per dl at 90 min after initiation of calcium infusion (P less than 0.01). Both amplitude and Dp/Dt of esophageal contractions decreased significantly in the skeletal muscle segment; however, amplitude and Dp/Dt increased significantly in the smooth muscle segment. Lower esophageal sphincter pressure remained unchanged. Duration of contractions and peristaltic wave speed were unaltered. Possible explanations for the divergent effect of hypercalcemia on the two types of esophageal muscle are discussed.


"Sucrose gap" technique for measurement of focal gastric mucosal potential differences in the rat. Bile salts, mechanical trauma, and ischemia were used to produce focal alterations in rat gastric mucosa in a chamber preparation. Gastric mucosal to serosal potential difference (PD) was measured from both treated and untreated areas using electrodes in contact with the mucosal surface. The sensitivity of the measurements was increased if a nonconducting solution (isotonic sucrose) was used to isolate electrically the control from the experimental sites. This "sucrose gap" technique thus allows the identification of focal areas of gastric mucosa with an altered PD. In addition, this technique was used to measure the PD of the forestomach, fundus, and antrum of the rat, and to demonstrate that atropine and pentagastrin influence the PD only in the fundus.


Rapid fall of serum phosphorus secondary to antacid therapy. Two patients with marked hypophosphatemia secondary to antacid therapy are described, 1 asymptomatic and the other symptomatic. In contrast to previous reports, these 2 patients were on aluminum hydroxide-containing antacids for relatively short periods of time before the hypophosphatemia occurred. Hypophosphatemia developed after only moderate doses of antacid in the symptomatic patient who was on a low phosphorus diet. An adequate intake of dietary phosphorus or phosphorus-containing antacids may be necessary to avoid a low serum phosphorus in patients taking aluminum hydroxide antacids even when the duration of therapy is as short as 2 weeks and the dose of antacids is not large.


Giant pseudopolyposis in colitis with colonic intussusception. When an area of giant pseudopolyp formation resulted in intussusception in a patient with known ulcerative colitis, operative intervention was required. The double contrast barium enema and fiberoptic colonoscopy were valuable complimentary diagnostic techniques in the evaluation of such a patient.


Diffuse ischemic colitis associated with systemic lupus erythematosus--response to subtotal colectomy. A 26-year-old woman with systemic lupus erythematosus developed massive rectal bleeding that failed to respond to medical treatment. X-rays and proctoscopy indicated that she had universal colitis. She underwent emergency subtotal colectomy because of a rapidly declining clinical course. The small intestine appeared normal. Pathological examination demonstrated a gangrenous large intestine, ischemic ulcerations, and extensive fibrinoid vasculitis that was typical of systemic lupus. The patient has had no further gastrointestinal complaints for 2 years since surgery.


Reversibility of hepatitis B virus-induced glomerulonephritis and chronic active hepatitis after spontaneous clearance of serum hepatitis B surface antigen. A patient presenting with nephrotic syndrome was found to have hepatitis B surface antigen-positive chronic active hepatitis and membranoproliferative glomerulonephritis. Glomeruli stained positive for hepatitis B surface antigen, IgG, and C1q. After spontaneous clearance of hepatitis B surface antigen both the glomerulonephritis and the chronic active hepatitis improved. The natural history, pathogenesis, and treatment of this disease complex are discussed.


[The value of roentgenography in the lateral projection for the conduct of breech delivery (author's transl)]. Breech delivery is still attended by considerably higher perinatal mortality and morbidity than is the normal presentation. Additional diagnostic methods are, therefore, needed for the safe conduct of breech deliveries. Roentgenograms in the lateral projection are a simple, but too rarely used, means that, in conjunction with the clinical findings, will provide essential information regarding the obstetric technique to be adopted. The objections to "X-ray diagnosis during pregnancy" are totally unfounded it Guthmann's single exposure technique is used. A retrospective analysis of 221 roentgenograms of breech presentation was correlated with the course of delivery. The results were highly informative in respect of both the pelvic abnormality and, especially, the therapeutic consequences. The X-ray evidence made it possible to reduce perinatal mortality (uncorrected) to 1.8 percent (generally stated to be 10--15 percent) and corrected mortality to nil.


[The problem of enterocele (author's transl)]. During the past nine years 70 enteroceles were observed. There were 27 primary and 43 secondary enteroceles. Etiologic factors were multiparity, advanced age, general lack of elasticity, obestiy, constipation and increased intra-abdominal pressure. The pathogenesis of primary enteroceles was usually to do a genital prolapse, tissue atrophy, a distended pouch of Douglas due to a tumour. The pathogenesis of secondary enterocele following previous uterine surgery was that at times the pre-existent enterocele had not been observed and the space between the uterosacral ligament and the rectum not been closed, or the patients had vaginal hysterectomies and anterior and posterior colporrhaphies, or the patients had previous uterine suspensions or abdominal hysterectomies. The interval between uterine surgery and enterocele was a mean 1.5 years for vaginal hysterectomies and a mean 15 years for the other operations. Different operative procedures for enterocele are discussed. In 90% of the cases the enteroceles were repaired vaginally by the method of Shaw O'Sullivan.


[Descending salpingitis following ruptured appendicitis (author's transl)]. The retrospective study of ovarian abscesses alerted us to the possibility of a descending salpingitis. The salpingitis arises from the pelvic periteneum following perforation of abscesses. Usually the fimbriated end remains open despite the inflammation. The pelvic peritonitis starts with ovarian abscesses, periappendiceal abscesses or complications of inflammatory intestinal diseases.


[Comments on the diagnosis of tubal pregnancy (author's transl)]. 51 women with suspected tubal pregnancy were admitted to our hospital during the past two years. Tubal pregnancy was present in 31 women. Diagnosis is rarely accurate with the conventional examination methods. The "LH/HCG" test was positive in all of our patients. Hence it appears resonable, whenever tubal pregnancy is suspected, to combine several noninvasive examination methods, special preference being given to the LH/HCG test.


[Comparison between intra and para cervical anaesthesia in therapeutic abortion (author's transl)]. Therapeutic abortion during the first trimester of pregnancy was carried out as an out-patient procedure under local anaesthesia in 40 women. The intracervical injection of 1% mepivacaine resulted in satisfactory freedom from pain just as the paracervical injection. There was no dignificant difference in the intensity of pain in intracervical and paracervical local anaesthesia. The dilatation of the cervical canal was the determining factor for pain during the procedure. The intracervical and the paracervical local block are equally suitable for out-patient therapeutic abortion in our series.


[Ultra sonography for the localization of intra-uterine contraceptive devices (i.u.d.'s) (author's transl)]. The localization of uterine devices by ultra-sound techniques was investigated. Seven different types of intra-uterine contraceptive devices were checked under immersion in water and in the uterus of 585 wearers of I.U.D.'s. The quality of the ultra-sound pictures is mostly determined by the type of intra-uterine device. Under optimal conditions the investigated types of I.U.D.'s produced standard ultra-sound pictures which permitted their identification. The evaluation of the localization of the intra-uterine contraceptive devices in the uterus was reasonably accurate. At first the classification of normal localization, lower segment localization and cervical localization was used, and this was later enlarged by the measurement of the distance between the uterine fundus and the end of the device closest to the fundus. It was possible to estimate the contraceptive efficiency with these measurements. In 486 cases (83%) the intra-uterine device was found in normal position. In 24 (4.1%) of the cases removal and repeat insertion of the device was suggested. In 18 (3.1%) cases the device was not localized despite normal intra-uterine localization.


[Conisation during pregnancy (author's transl)]. The paper reviews 15 cases undergoing conisation during pregnancy. In 2 conisation was immediately followed by radical operation for invasive squamous carcinoma. 11 patients had pre-invasive carcinoma by microscopic evidence on serial step sections, while the remaining 2 showed high-grade dysplasia of the cervix. Atypical tissue was successfully removed in toto in 6 of the 8 cases with lesions predominantly localizing at the cervical surface. Of the 5 abnormal epithelial processes which were almost entirely endocervical only 1 was completely removed. Abortion occurred in 4 of the 13 patients undergoing conisation without prophylactic cerclage. Shirodkar's operation was done at the time of conisation in 7 cases, in one after an interval of 10 weeks. This prophylactic measure failed to prevent prematurity in 2 cases, while the remaining 6 gave birth to living and mature infants between the 37th and the 40th week of gestation.


[Percutaneous antegrade needle hydronephrosis as an emergency measure in the management (author's transl)]. The needle of acute aspiration of the pyelon assures immediate drainage of the urine in a hydronephrosis with a distended calceal system. This emergency measure often is necessary in acute high risk cases which are often gynecological cases. A cannula for percutaneous needle aspiration of the kidney basin is presented. With this cannula antegrade percutaneous translumbar needle drainage of the kidney basin is possible without operative risk. Operative exposure of a hydronephrotic kidney with the only aim of nephrostomy can be avoided with this method in most cases.


[Bilateral carcinoma of the breast after radiotherapy and chemotherapy for Hodgkin's disease (author's transl)]. A 34-year-old patient had radiotherapy and chemotherapy for Hodgkin's disease of the nodular sclerosing type 2 A thirteen years prior to the treatment of a right cancer of the breast in the stage M0 N1 T3. Seven months later the patient had a left cancer of the breast in the stage M0 N0 T4. The literature is reviewed and the possibility of occurrance of secondary carcinoma following treatment of Hodgkin's disease is discussed.


[Determination of microelements in the human placenta. III. Commun.: atomic-absorption spectrophotometric determination of Zn, Cu, Cd, Mn, Fe, and Mg contents of human placentas (author's transl)]. In human placentas from the West Berlin area is the content on Zn, Cu, Cd, Mn, Fe, and Mg determined by means of the flameless and the flame atom absorption spectrophotometry, respectively.


Four common ocular complications of diabetes--and how to treat them. To minimize the risk of visual loss in diabetic patients, recognition of early signs of oculopathy is essential. Diabetes-associated third-nerve palsy is manifested by unilateral ptosis and exotropia. Symptoms of closed-angle glaucoma are intense pain, halos around lights, and blurred vision. Open-angle glaucoma does not necessarily produce symptoms and is treated medically. A gradual decrease in visual acuity, sometimes associated with photophobia and difficulty in night driving, and monocular diplopia, are manifestations of cataract. The patient with "background" retinopathy usually complains of blurred or distorted central vision. Once the macula is involved, vision progressively decreases. Although the relationship of metabolic control to retinopathy has not been settled, evidence indicates that good medical control of the disease may delay onset of vascular complications.


Should you treat systolic hypertension in elderly patients? Systolic hypertension is difficult to control in the elderly, but this is not an excuse for denying these patients the benefits of carefully controlled antihypertensive treatment, particularly when target organ disease is present. Although drug therapy may produce alarming symptoms, it is highly doubtful that it increases the incidence of myocardial infarction or permanent neurologic damage. In fact, evidence indicates that antihypertensive therapy may prevent hemorrhagic and thrombotic strokes. Arterial pressure should be reduced slowly and cautiously--to allow control without interfering with cerebral flow stability. Drug therapy should be started in small doses and may be initiated with diuretics. Methyldopa in small or moderate doses has been effective and does not often cause postural hypotension. Drugs that interfere with reflex arteriolar constriction should not be used.


Intestinal stomas: managing the "unmentionable". Learning to live with an intestinal stoma is a difficult adjustment for elderly patients. Thoughtful, sensitive preoperative counseling and postoperative education in caring for the stoma are essential, and both are often the responsibility of the primary care physician. Irrigation is the preferred method of colostomy management, and with proper instruction, most patients can learn the technique. The physician and nurse should work in concert to teach patients how to control bowel movements, prevent odor, and maintain the integrity of the stoma and the skin. Elderly patients are able to accept a stoma much more readily if they can manage it easily.


Can you recognize and treat mycosis fungoides? Whenever lesions resembling psoriasis or nummular eczema remain unchanged for several months or do not respond to topical steroid therapy, mycosis fungoides should be suspected and multiple biopsies performed. Early diagnosis increases the possibility of destroying malignant cells before they involve internal organs. Early treatment is usually conservative, with topical steroids and occlusion. Topical nitrogen mustard, oral psoralens, long-wave ultraviolet light, and--ultimately--radiation are used as the disease progresses. Use of whole-body electron beam therapy appears promising.


What we know--and don't know--about bone loss in the elderly. The incidence of fracture in women increases with age; yet studies of age-associated bone loss have shown conflicting results. Cross-sectional studies show that variation in bone content does not increase significantly with age, supporting the theory that there is a universal bone loss with age, and that women with low initial bone mineral are the most susceptible to osteoporosis. On the other hand, prospective studies show that people do lose bone at different rates. Both types of studies indicate that the rate of bone loss is significantly lower in elderly women than in those in the early postmenopausal period. The hallmark of osteoporosis is vertebral fracture, which is most often asymptomatic and increases in incidence in elderly women. However, there is considerable overlap in the amount of bone mineral in those with fracture and those without fracture. The overlap at fracture sites may indicate that factors other than low bone mass--such as osteomalacia--may play an important role in the development of fracture.


Techniques for communicating with your elderly patient. A physician can best treat elderly patients if he or she understands their unique problems and employs effective techniques of communication. Be aware how your patient's anxiety or your own view about the elderly can erect a barrier to communication. Your position in the room, your tone of voice, your touch all communicate--either positively or negatively--to your elderly patient.


Histamine and insulin dose-response studies of gastric secretion in Indian control subjects and patients with duodenal ulcer in the Ganges delta. The gastric secretory responses to various doses of histamine and insulin have been studied in 11 control and 12 duodenal ulcer subjects belonging to the Ganges delta of India where the incidence of duodenal ulcer disease is known to be high. A dose of 0.04 mg/kg body weight of histamine acid phosphate was sufficient to produce peak gastric acid output both in the control and duodenal ulcer subjects. However, a dose as low as 0.025 U insulin/kg body weight was enough to produce peak rates of gastric acid output in duodenal ulcer subjects, whereas in the controls a minimum dose of 0.05 U insulin/kg body weight was sufficient. A greater proportion of the duodenal ulcer patients also showed a peak acid secretory response in the first hour after administration of insulin. Furthermore, increasing doses of insulin in this population did not produce lower levels of blood glucose but did produce increasingly high acid output as subjects do in the West. K values derived from the intravenous glucose tolerance test showed that 75% of duodenal ulcer patients and 54% of the controls had variable degrees of intolerance to glucose. Gastric acid secretion in response to a bolus of 50 ml 50% intravenous glucose was also studied in a separate group of 16 duodenal ulcer and 13 control subjects. A sharp rise in the volume, titratable acidity, and total acid output was observed in the early part of the fourth hour in the control and duodenal ulcer subjects. In a separate group of controls a bolus of intravenous hypertonic saline produced no such increase in gastric acid secretion.


Availability of monoglutamyl and polyglutamyl folates in normal subjects and in patients with coeliac sprue. Intestinal folate absorption was assessed in six normal subjects and in four patients with coeliac sprue who were studied before and after treatment by dietary gluten exclusion. Comparisons were made of the luminal disappearance from the perfused jejunum of 3H-pteroylmonoglutamate and pteroyl 14C-glutamylhexaglutamate, and of the 48-hour urinary recovery of each isotope after perfusion and a tissue saturating dose of folic acid. The labelled urinary folates consisted of folic acid, 10-formyltetrahydrofolate, and 5-methyltetrahydrofolate. In each group urinary recovery of 3H was significantly greater than that of 14C, confirming the evidence from jejunal perfusion that the availability of monoglutamyl folate is greater than that of polyglutamyl folate. According to the urinary recovery data, both folates were poorly absorbed in untreated coeliac sprue, but were normally absorbed after treatment. Assuming uniform displacement of the absorbed labelled folates by the parenteral flushing dose, the finding of greater urinary isotope recovery than of luminal folate disappearance from the perfused proximal jejunal segment suggests an adaptation of the distal small bowel for folate absorption in coeliac sprue.


Lundh test and ERCP in pancreatic disease. The Lundh test and endoscopic retrograde cholangiopancreatography (ERCP) were used to investigate 40 patients with known or suspected pancreatic disease. Pancreatograms were classified as being normal or showing minimal or gross changes. There was good correlation between the two tests in assessing the degree of pancreatic disease (P less than 0.01). Gross radiographic changes were associated with a mean tryptic activity (MTA) of less than 6 IU/ml, while minimal changes were associated with an MTA between 6 and 14 IU/ml. Although some patients with normal pancreatograms had MTAs within this range, no patients with an MTA above 14 IU/ml had an abnormal pancreatogram. The Lundh meal is of great value in detecting extensive pancreatic disease and an unequivocally normal result virtually excludes significant chronic pancreatic disease. Values in the equivocal range usefully draw attention to early pancreatitis which may be confirmed by ERCP. In this paper the interpretation of pancreatograms is discussed and the clinical features of the patients with minimal change disease are reviewed.


Comparison of rectosigmoid myoelectrical activity in the irritable colon syndrome during relapses and remissions. Recent studies have suggested that a high incidence of 0.05 Hz (3 c/m) slow wave electrical activity is present within the rectosigmoid of patients with the irritable colon syndrome during symptomatic phases. However, it is known that this is a chronic relapsing disorder and in this study we have compared myoelectrical recordings, using an on-line frequency analyser, during periods of severe symptoms and asymptomatic phases. Treatment with either bran (in the form of bran tablets) or an antispasmodic resulted in 12 of the 20 patients becoming free from symptoms after one to three months. In those patients who were initially constipated a statistically significant increase in mean stool weight and a decrease in mean transit time occurred, but this was not associated with any alteration in either percentage motility or electrical activity. In patients with predominant diarrhoea no statistically significant difference occurred in either transit time or stool weight after treatment nor did the abnormal myoelectrical activity return towards normal with symptomatic improvement. These results suggest that a fixed basic myoelectrical abnormality exists which is unrelated to symptoms. This may help to explain the chronic relapsing nature of the irritable colon syndrome.


Serum factor affecting neutrophil function during acute viral hepatitis. Sera from eight of 17 patients with acute viral hepatitis was deficient in its ability to support neutrophil bactericidal function in vitro. This defect appeared to be related to the viral infection itself. Sera from patients with drug hepatitis or mechanical obstructive jaundice did not show this effect.


Portal and systemic bacteraemia and endotoxaemia in liver disease. Using a percutaneous transhepatic technique, blood was obtained from the portal veins of 30 patients with various hepatic disorders and examined for the presence of bacteria and endotoxin. Simultaneous samples also were drawn from hepatic and peripheral veins. In three cases, portal vein cultures grew diphtheroids, which were of doubtful significance, while all hepatic and peripheral cultures were sterile. Endotoxin was detected in seven portal vein samples; in none of these patients were the hepatic or peripheral blood samples positive. In three cases, only peripheral blood samples were positive for endotoxin. It was concluded that portal bacteraemia occurs as infrequently in patients with liver disease as in those without. Portal endotoxaemia was detected in patients with all degrees of liver disease but, even in patients with moderately severe portal hypertension, the liver may remain an effective filter of endotoxin.


Gastric emptying after treatment of stenosis secondary to duodenal ulceration by proximal gastric vagotomy and duodenoplasty or pyloric dilatation. A consecutive series of 12 patients with stenosis secondary to duodenal ulceration were treated by proximal gastric vagotomy (PGV) and duodenoplasty or PGV and dilatation of the stenosis. Three months after operation the rate and pattern of gastric emptying of a solid meal was measured in each patient and compared with 18 patients with uncomplicated duodenal ulcer treated by PGV alone. Two patients developed gastric stasis in the early postoperative period which resolved with medical treatment. All patients were asymptomatic and were eating normally three months after operation. There was no significant difference in the rate of gastric emptying postoperatively between the patients who had stenosis and those who had uncomplicated duodenal ulcers. These results indicate that despite early postoperative difficulties in some patients pyloric dilatation or duodenoplasty with PGV are both effective treatments for stenosis due to duodenal ulceration.


Treatment of encephalopathy during fulminant hepatic failure by haemodialysis with high permeability membrane. Forty-one patients with fulminant hepatic failure and coma underwent 180 periods of haemodialysis with polyacrylonitrile membrane (AN 69 HD). Hepatic failure was due to viral hepatitis in 40 and drugs in one. Total recovery of consciousness occurred in 17 patients (43.6%), and partial in seven (17.9%)--that is, an overall figure of 61.5%. Regain of consciousness was not related to liver regeneration as assessed by levels of factor V and hepatocyte volume fraction. At the time of the first haemodialysis, neurological status was significantly impaired in the patients who could not be aroused. Mean duration of coma grade IV averaged 6.1 +/- 4.3 days and mean duration of illness until death or decerebration 8.6 +/- 8.3 days. Of the 17 patients who totally regained consciousness, nine recovered and eight died (three from intercurrent complications and five with no liver regeneration).


Increased serum immunoreactive gastrin levels in idiopathic hypertrophic pyloric stenosis. The serum immunoreactive gastrin (IRG) level in infants with confirmed idiopathic hypertrophic pyloric stenosis (IHPS) has been determined and compared to that found in vomiting infants without IHPS, in normal infants, and in normal adults. The mean serum IRG level of normal infants (103 +/- 9 pg/ml (mean +/- SEM) exceeded that of normal adults (28 +/- 5 pg/ml). The preoperative mean serum IRG level in IHPS infants (256 +/- 26 pg/ml) was significantly higher than that of both normal infants and vomiting infants without IHPS (93 +/- 9 pg/ml). Twenty-five per cent (5/20) of the IHPS infants had serum IRG levels within the upper range of normal infants. Fasting serum IRG levels in IHPS infants were not altered immediately by pyloromyotomy. The results from this study suggest a relationship between gastrin and idiopathic hypertrophic pyloric stenosis.


Parietal cell hyperplasia induced by long-term administration of antacids to rats. Suspension of magnesium and aluminum hydroxide (30--60 mEq/24h) or a comparable volme of water was orally administered by gastric intubation to two groups of 20 male Wistar rats each over 60 days. The antacid treatment led to a significant increase in the height (0.464 +/- 0.02 mm v. 0.318 +/- 0.06) and in the volume (472 +/- 32 mm3v.328 +/- 45) of the fundic mucosa of the stomach, in the average count of parietal cells per unit area of the mucosa (32.37 +/- 1.8 v. 22.3 +/- 1.6), and in the total parietal cell population of the stomach (53.6 +/- 3.5 x 10(6) v. 43.2 +/- 3.7 x 10(6)). Furthermore fasting serum gastrin concentration was significantly higher in the antacid treated rats (81.2 +/- 7.4 pg/ml) than in control animals (56.9 +/- 6.9 pg/ml).


Drug metabolism in hepatosplenic schistosomiasis in the Sudan: a study with antipyrine. The disposition of antipyrine following oral administration of 1200 mg has been investigated in 10 patients with histologically confirmed hepatosplenic schistosomiasis and 11 normal subjects living in Sudan. Drug metabolising activity as assessed by antipyrine clearance was similar in patients when compared with normal controls. We conclude that antipyrine disposition is normal in patients with clinically compensated hepatosplenic schistosomiasis.


Suppression of rejection of Nippostrongylus brasiliensis in iron and protein deficient rats: effect of syngeneic lymphocyte transfer. Rejection of Nippostrongylus brasiliensis is impaired in iron and protein deficient rats and this suggests that iron and protein deficiency directly or indirectly suppresses the immune response. The site of the immunological defect in deficient rats was investigated using the technique of cellular transfer of resistance. The functional activity of immune mesenteric lymph node cells obtained from iron and protein deficient donors was not depressed as measured by their capacity to cause parasite rejection in nutritionally sufficient recipients. In contrast, immune lymph node cells obtained from either sufficient or deficient donors did not result in parasite rejection in iron and protein deficient recipients. These results indicate that there is no permanent defect of lymphocyte function in iron and protein deficient rats and suggest that either some other component of the rejection mechanism is defective, or that lymphocyte function is blocked in an iron and protein deficient environment.


Relationship of the constituents of bile to biliary peritonitis in the rat. The local action of bile salts has been associated with a wide variety of gastrointestinal diseases. This paper describes an animal model to determine which of the major solid components of bile are responsible for peritoneal destruction in biliary peritonitis. In the rat, bile salts within the peritoneal cavity cause peritonitis but cholesterol and lecithin are without deleterious effect.


Membrane lipid composition of red blood cells in liver disease: regression of spur cell anaemia after infusion of polyunsaturated phosphatidylcholine. The morphology of red blood cells was studied in 30 patients with severe liver cirrhosis, in 10 patients with extrahepatic jaundice, and in 10 control subjects. In all the patients with extrahepatic jaundice more than 30% of red blood cells were target cells with increased resistance to osmotic lysis. In 12 patients with liver cirrhosis more than 30% of red blood cells were spur cells. The cholesterol: phospholipids (C/PL) molar ratio was 0.89 in target cells, 1.33 in spur cells, and 0.74 in normal red blood cells. The red blood cell membrane cholesterol and phospholipids exchanged with plasma lipoproteins, the lipid composition of which was studied in eight patients with spur cells; the free cholesterol: phospholipid (FC/PL) molar ratio was 0.33 (0.16 in the controls) in high density lipoproteins (HDL) and 1.40 (0.82 in the controls) in low density lipoproteins (LDL); in these patients the polyunsaturated fatty acid content was low in both phospholipids and cholesterol esters of lipoproteins. The irregular folds of the spur cells regressed when polyunsaturated lecithin was infused (2 g daily for five days) in eight patients with spur cell anaemia; the infusions decreased both C/PL ratio in RC to 0.88 and the concentration of unconjugated bilirubin (104.3 to 82.0 mumol/l (6.1 to 4.8 mg%)), whereas the activity of the plasma lecithin:cholesterol acyltransferase (LCAT) increased from 31.2 to 54.4 mumol/l/h. Polyunsaturated fatty acid content of RC lecithin increased after the infusion as it did in HDL, the FC/PL ratio of which decreased to 0.23.


Ultrastructural study of gonads in the complete and incomplete feminization syndrome. The gonads of two individuals with complete and one with incomplete testicular feminization were examined by light and electron microscopy. In the seminiferous tubules of the complete forms, clear, intermediate, and dark-type Sertoli cells could be distinguished. These are immature elements which had assumed, under the influence of hormones, different morphology. Leydig cells were also immature, at varying stages of differentiation. In the complete form Sertoli and Leydig cells had an almost normal fine structure; the lamina basalis of the tubules, however, was considerably thickened.


Energy metabolism in the exteriorized fetus. Umbilical blood flow rate (UBF) was measured in 9 exteriorized fetal lambs by weight changes of the fetus during total umbilical vein occlusion. Concentrations of oxygen, lactate and pyruvate in umbilical arterial (UA) and umbilical venous (UV) blood were determined. Rate of fetal oxygen consumption (.QO2) was 5.2 +/- (SEM) 0.48 ml. kg(-1) . min (-1), and was correlated with UBF (r = 0.793), but not with the content of O2 in UA or UV. The UV-UA differences in lactate/pyruvate ratios indicated varying degrees of anaerobic metabolism in those fetuses with highest UBF and .QO2, but not in poorly perfused fetuses with low .QO2. Fetal exteriorization can result in inadequate perfusion of fetal tissue, lowering of fetal oxygen consumption and some anaerobic metabolism.


Fine structure of the human placenta in prolonged pregnancy. Preliminary report. Placentas from 15 prolonged (is greater than 42 weeks), but otherwise normal pregnancies, and 8 normal-term placentas were studied. Placental villi from term placentas revealed intact syncytial and cytotrophoblast elements. All term placentas presented a minimal to mild degree of villous necrosis and deposition of fibrinoid material. Placental villi from cases of prolonged pregnancy presented a moderate to severe degree of necrosis in 11 of 15 placentas and a minimal to mild degree in 4 of 15 placentas. A moderate to severe degree of fibrinoid deposition was noted in 7 of 15 placentas, whilst 8 of 15 revealed a minimal to mild degree of deposition. The presence or absence of meconium was noted in the prolonged-pregnancy group and correlated with the above morphological features. Statistically, a correlation was found between prolonged pregnancy and necrosis (p is less than 0.001), prolonged pregnancy and fibrinoid deposition (p is less than 0.03) and between necrosis and deposition of fibrinoid (p is less than 0.05). There was no correlation between the incidence of meconium staining and the above parameters.


Estriol antagonism of the action of bradykinin and adrenalin on human umbilical artery. The effect of estriol on the response of human umbilical artery to bradykinin (0.2 microgram/ml) and adrenalin (0.8 microgram/ml) was studied by an in vitro perfusion method. Estriol (10 microgram/ml) added to the nutrient medium decreased the response of the preparation to the two vasoactive agents. The results suggest the participation of estriol as a modulator of the vascular response at the level of the umbilical circulation, where it may act to protect the maternal-fetal circulatory system from physical or chemical stimuli.


Dupuytren's disease--the influence of occupation and previous hand injuries. The influence of handedness, work and previous hand trauma is studied in 901 persons with Dupuytren's disease, collected in an epidemiological study of 15,950 citizens in a small, Norwegian town. Dupuytren's disease occurred in all occupational groups, but the prevalence was higher and the contracture more severe in people doing hard manual work than in people doing light or non manual work. Persons with Dupuytren's disease has sustained previous hand trauma more frequently than the general population, and the interval between trauma and first sign of disease was usually a few years. Previous hand injuries were definitely more common among people doing hard manual work, but even when these were excluded from the work material, Dupuytren's disease was still more common among people doing hard manual work, than in people doing light or non manual work. The study has indicated that Dupuytren's disease in certain cases is precipitated and/or aggravated by both work and definite hand injury.


The treatment of squamous cell carcinoma of the hand. This paper is a review of a series of forty-four patients with squamous cell carcinoma of the hand. The various forms of treatment carried out are outlined and the results reported.


Reconstruction of the digital tendon-sheath in "no-man's" land with autologous transplanted vein-graft. A two-stage procedure is described for severely damaged flexor tendons in "no man's land". In the first stage the damaged tendons and scarred tendon sheath are excised and a segment of the saphenous vein, cannulated by a silicone rubber rod is transplanted into the tendon bed. In the second stage the silicone-rod is replaced by a free transplanted tendon. The endothelial lining of the vein is a guarantee of a good gliding surface and an obstacle to adhesion formation, and so it ensures good function. A review of the method and a survey of thirty-nine cases are presented.


The length of flexor tendon grafts.

The length of flexor tendon grafts. The distance between the origin of the lumbrical muscle and the insertion of the flexor digitorum profundus tendon was measured at surgery in forty-eight patients. It was found that this distance was predictable and could be estimated without measurement prior to operation. A standard technique of flexor tendon grafting is described where this distance equals the length of the tendon graft.


Avulsion of the ring finger flexor digitorum profundus tendon: an experimental study. The results of an experimental study of the breaking strength of the tendon-bone junction of the flexor digitorum profundus tendon in cadaver specimens indicates a significantly weaker insertion of the ring finger compared to the middle finger. This explains in part the more frequent occurrence of avulsion of the ring finger profundus tendon as observed clinically.


Upper-limb-cardiovascular syndrome. Two cases of Holt-Oram syndrome. Two cases of Holt-Oram syndrome with an atrial septal defect and thumb deformities are reported. The embryological basis for the association between skeletal malformations particularly of the hand, and congenital heart disease, is discussed.


Long-term results of ulnar to median nerve pedicle grafts. Nerve pedicle grafts in the upper limb were performed on nine patients with Volkmann's Ischaemia. Long-term follow-up of three cases has shown that the results of this operation are successful. Sensory and motor recovery of the median nerve occurs and consequently useful hand function is regained. Since Volkmann's Ischaemic contracture is not rare in developing countries, this operation should be the treatment of choice when the median and ulnar nerves have been damaged beyond hope of recovery.


Carpal tunnel syndrome due to thrombosed persisting median artery. A case report. Surgical intervention for carpal tunnel syndrome in a seventy year old woman revealed thrombosis of a double persisting median artery. The persisting median artery is a rare anomaly and its association with a thrombotic process to cause carpal tunnel syndrome is even rarer. Carpal tunnel syndrome is a widely-known phenomenon about which much has been written in the medical literature. A persisting median artery accompanying the nerve into the carpal tunnel is uncommon, occurring in only about 10% of such cases (Pecket, 1973) and thrombosis of such an artery as a cause for carpal tunnel syndrome is very rare (Burnham, 1963; DeAbreu & Godoy Moreira, 1958). We describe a case in which thrombosis is a double persisting median artery was discovered to be the cause of carpal tunnel syndrome at operation.


Saint Anthony's fire or carpal tunnel syndrome? (a case of iatrogenic ergotism). A case of unilateral upper limb ischaemia from ergot overdosage is presented. An unusual feature was a median nerve neuropathy suggestive of carpal tunnel syndrome. The arteriographic appearances are demonstrated and management discussed.


Racquet player's pisiform.

Racquet player's pisiform. Four patients whose sport involved wielding a racquet presented with symptoms at the base of the hypothenar eminence which were due to minor degrees of subluxation of the pisiform. In two there was in addition a chondromalacia of the articular cartilage of the joint.


Three-dimensional architecture of blood vessels of tendons demonstrated by corrosion casts. Three-dimensional observation of the microcirculation of the tendon was readily and clearly demonstrated by preparing methyl methacrylate casts and observing them under the scanning electron microscope. In the muscles blood vessels made a network like a ladder surrounding every muscle fibre. The fibrous digital sheath had blood vessels made in a fine meshed cylinder. By microdissection of the vessels of the sheath the blood vessels of the vinculae and tendons were observed stereoscopically in relation to the peritendinous tissues. The casting method contributes to better understanding of vascular architecture of tendons.


The conservative treatment of the Swan-Neck deformity in the rheumatoid hand. A technique is described to correct rheumatoid Swan-Neck deformity in those patients where there is limited proximal interphalangeal joint flexion in all positions. It involves the manipulation of these joints and their temporary immobilisation with Kirschner wires followed by mobilisation using an elastic band method.


The use of the Flatt hinge prosthesis in the rheumatoid thumb. Nine patients with marked destruction in both the metacarpophalangeal and interphalangeal joints of the thumb, were treated with fusion of the interphalangeal joint and insertion of the Flatt hinged metal prosthesis into the metacarpophalangeal joint. Of the nine thumbs treated in this manner, eight had good to excellent results. One prosthesis was removed after it became infected, leaving both joints fused.


Microvascular great toe transfer for congenital absence of the thumb. Two cases of microvascular great toe transfer for congenital absence of the thumb in children are reported. A rationale and operative details are discussed. A long term follow up is needed, but at this stage the results are most encouraging. There has been no interference with gait.


A comparison of three techniques of micro nerve repairs in dogs. An assessment of the results of three techniques of nerve repair. Epineurial repair, Funicular repair with resection of epineurium and Combined Funicular and Epineurial repair. The results were essentially similar.


The determinants of flexor tendon fibrosis following trauma: an experimental study in rabbits. Twenty-six rabbits were subjected to various types of forepaw flexor tendon laceration. After two weeks the tendons were examined. Fibrosis was densest around the proximal stump of the divided profundus tendon. Double partial transverse nicks, designed to induce local ischaemia, caused no more fibrosis than a single longitudinal slit of the same length. Rendering the proximal stump ischaemic with a snare caused no increase in fibrosis. It was concluded that movement and tissue trauma are more important than ischaemia in determining the degree of fibrosis around the injured flexor tendon in the rabbit forepaw.


Primary repair of flexor tendons within the digital theca of the hand. The results of primary repair of the flexor tendons within the digital theca of the hand in twenty-three fingers have been very encouraging. Eighty-seven percent of the fingers had excellent to good results. Primary tenorrhapy by the technique described in selected cases offers the patient a shorter period of disablement with functional results as good or even better than those after a free tendon graft.


Restoration of opposition of the thumb.

Restoration of opposition of the thumb. During the period 1966--75 operation to restore thumb opposition was performed in thirty four patients. Out of twenty seven patients who could be traced, twenty one had obtained a satisfactory result, five had considerably improved, while one had to be classified as a failure. Complications from the operation and the motor tendon are discussed. Among 147 cases with injury to the median nerve treated during the same period, operation to obtain opposition was indicated in 14%.


Compression of the deep palmar branch of the ulnar nerve by the arch of the adductor pollicis. A case of palsy of the distal part of the deep palmar branch of the ulnar nerve is described. The possibility of an entrapment by the arch of the adductor pollicis is discussed. Anatomical features of this arch are reported.


Fracture of the hook of the hamate presenting as carpal tunnel syndrome. This case report of a fracture of the hook of the hamate presenting as carpal tunnel syndrome emphasizes the importance of a careful physical examination, the necessity for a carpal tunnel roentgenogram and a high degree of suspicion by the surgeon in patients with symptoms of median nerve compression following trauma to the wrist.


Bone density and the carpal tunnel syndrome. Bone density was studied in ten patients before and after release of an idiopathic carpal tunnel syndrome. A corticomedullary ratio was measured at the mid-point of the metacarpals and proximal phalanges of both hands. There was a significant increase in the mean bone density over the period of observation in the thumb and middle finger metacarpals and in the index, middle, and ring finger proximal phalanges of the operated hand. There was no significant increase in the density of either metacarpal or proximal phalanx on the non-operated side. Release of the carpal tunnel syndrome provides not only symptomatic relief but also leads to increased bone density.


The effects of sural nerve excision in autogenous nerve grafting. The effect of excising fifty sural nerves from the legs of forty-five patients undergoing nerve grafting are described. Forty-two per cent of patients complained of tenderness in the calf, likely to be due to neuroma formation. Ten per cent of patients had other minor complaints. One would haematoma and one deep vein thrombosis occurred. Overall patient satisfaction was high when the functional result of the nerve grafting was taken into account.


Metacarpal shortening.

Metacarpal shortening. A case of Psoriatic Arthritis with disabling flexion deformities at the metacarpo-phalangeal joints of the fingers is described. Skeletal shortening decreased the deformity and improved the function.


Acute flexor tenosynovitis caused by gonococcal infection. A case report. Gonococcal infection of tendon synovial sheath is discussed. A case of acute gonococcal flexor tenosynovitis without joint involvement is presented.


Tooth fragment in a metacarpophalangeal joint. A patient with septic arthritis and a retained tooth fragment in a metacarpophalangeal joint is described. The case illustrates the mechanism of the initial injury.


[Observation of animal behavior by revolving activity cage method: A new automatic measuring and recording system of motor activity of a mouse by means of revolving activity cage is presented (author's transl)]. With this system, several parameters can be recorded continuously over several months without exterior stimuli. Time per revolution is counted and punched into the paper tape as binary coded numbers, and the number of revolutions and the frequency of "passage" in a given time are printed out on a rolled paper by a digital recorder. "Passage" is defined as one revolving trial without a pause over a fixed time (criterion time) and used as a behavioral unit of "stop and go". The raw data on the paper tape are processed and analyzed with a general-purpose computer. It was confirmed that when a mouse became well accustomed to the revolving activity cage, the time per revolution followed the law of exponential distribution probability, while the length of passage (i.e. the number of revolutions per revolving trial) followed that of geometrical distribution probability. The revolving activity of mice treated with single subcutaneous injection of methamphetamine was examined using these parameters.


[Distribution, metabolism and excretion of toluene in mice (author's transl)]. Tissue distribution, metabolism and excretion of 14C-labeled toluene were investigated after a single intraperitoneal administration (290 microgram/kg) of the compound into mice. The highest radioactivity was detected in the adipose tissue, followed in descending order by the kidney, liver and lung. The lowest radioactivity was retained in brain tissue and the brain/blood concentration ratio was about 0.4 throughout. Radioactivity in the blood declined exponentially and the biological half-life was estimated to be 25 min. Radioactive materials detected at as early as 8 min in the kidney (78%) and liver (64%) proved to be non-volatile metabolites. On the contrary, 70% of radioactive materials in the brain and near 100% in the adipose tissue were found to be a volatie compound (probably unchanged toluene). The cumulative urinary excretion of radio-activity was 26.4% of the dose at 30 min and 73.8% at 18 hr, whereas the pulmonary or fecal excretion was negligibly small. Radioactive materials excreted in the urine were identified by paper and the thin-layer chromatography as hippuric acid (59%) and benzoylglucuronic acid (41%). These results show that toluene is metabolized rapidly and is excreted mainly in the urine. The relative importance of glucuronide formation in detoxication mechanisms was noted.


[Experimental asthma in rats, and the effect of N (3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5') (author's transl)]. Although guinea pigs have been frequently used as a model of asthma, antibodies produced in this species are generally gamma1 and gamma2 and belong to IgG. The antibody responsible for asthmatic attacks in humans is IgE, and such is quite different from gamma1 and gamma2, immunologically. Guinea pigs are not therefore an adequate model for investigating anti-asthmatic drugs which inhibit IgE-mediated mediator release, such as disodium cromoglycate. On the other hand, rats do produce an antibody similar to human IgE, the so-called homocytotropic antibody (HTA), by sensitization with dinitrophenylated ascaris extract (DNP-As) together with killed Bordetella pertussis as an adjuvant. To rats actively sensitized with DNP-As or passively sensitized with HTA serum against DNP-As, intravenous administration of antigen did not produce a transient increase in respiration (unlike that of guinea pigs) immediately after the antigen treatment, but a respiratory disorder similar to that seen during asthmatic attacks in humans did occur. The response to antigen was reproducible in passively sensitized rats compared with that of actively sensitized ones, though the symptom was moderate. The effect of N(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-allergic drug, was determined in cases of experimental asthma in passively sensitized rats. Respiratory disorders as a result of antigen were clearly inhibited with oral administration of this agent.


[Effects of a vitamin B complex on functional recovery after nerve injury (author's transl)]. Functional recovery after nerve crushing was investigated in the following manner: Under pentobarbital anesthesia the sciatic nerve of the rat was crushed at the level of the hip (proximal crush) or the thigh (distal crush). The recovery processes after the nerve crushing were followed by measuring distances between the first and fifth digits(DBD.1 approximately 5) and between the second and fourth digits (DBD.2 approximately 4) of the hind paw, and by observing changes in "behavior" scored on a scale of 10 according to the degree of behavioral disorder of the hind paw and leg. Results obtained by these methods showed good reproducibility. The DBD values and the scores for behavior recovered significantly faster after weak nerve crushing than after strong crushing, and after distal rather than after proximal crushing. When a segment of the sciatic nerve was resected, there was no recovery. These results suggest that DBD.1 approximately 5, DBD.2 approximately 4, and the behavior observed in these experiments serve as good indices for evaluating the degree of functional recovery after nerve injury in unanesthetized and unrestrained animals. Effects of a preparation of vitamins B1, B6, and B12 (B complex) on these three parameters and on weights of 9 muscles of the hind leg were also studied. These studies showed that the B complex facilitated functional recovery from nerve injury faster than its components, and that on muscle atrophy the B complex had its most effects on the soleus. It was also shown that B1 and B12 by themselves had significant facilitating effects on the functional recovery.


[Anti-inflammatory activity of SL-573 (author's transl)]. In the carrageenin-induced edema test in rats, the anti-inflammatory activity of SL-573 was 1.6 times as potent as those of phenylbutazone (PB) and ibuprofen (IP), 3.3 times as potent as that of mefenamic acid (MF) and 6.7 times as potent as that of mepirizole (MP). In the yeast-induced edema test in rats, SL-573 showed equipotent activity with IP, the activity of which was 4 times as potent as that of MP. In the dextran-induced edema test in rats, the anti-inflammatory activity of SL-573 was significantly higher than those of IP and MP. SL-573 showed no anti-inflammatory activity in the formalin-induced edema test in rats in the same way as seen with IP and MP. SL-573 markedly inhibited the increase in capillary permeability in mice induced by intraperitoneal administration of acetic acid, and its activity was 12 times as potent as that of PB and 17 times as potent as that of MF. SL-573 showed anti-granuloma activity neither systemically nor locally. SL-573 showed equi-potent activity with PB in the adjuvant arthritis test in rats and had little effect on the healing process of the skin wound in rats. The effect of SL-573 on the carrageenin-induced edema was not diminished in the adrenalectomized rats. The gastric bleeding effect of SL-573 was significantly weaker than that usually seen in nonsteroidal anti-inflammatory drugs. SL-573 did not induce intestinal perforation even at the high dose of 800 mg/kg. Additionally, SL-573 showed a protective effect on the indomethacin-induced intestinal lesions. These pharmacological profiles of SL-573 were considered to be quite characteristic as compared with those of known nonsteroidal anti-inflammatory agents.


[Evidence for existence of type A MAO in mitochondria from human placenta (author's transl)]. The existence of type A and B MAO in mitochondria from human placenta was investigated on the basis of inhibitions by selective MAO inhibitors, such as clorgyline (type A inhibitor) and pargyline and deprenyl (type B inhibitors) with serotonin (substrate for type A MAO), tyramine (substrate for both types of MAO) and beta-phenylethylamine (substrate for type B MAO) as substrates and the results were compared with those obtained with MAO in rat liver. The rates of serotonin, beta-phenylethylamine and benzylamine oxidations by placental MAO were approximately 191, 12 and 48% to those of rat liver MAO, respectively. Placental MAO was more sensitive to tryptic digestion than the enzyme in rat liver. Both MAO's could be separated into two fractions by sucrose density gradient centrifugation, but the two types could not be distinguished when inhibitor sensitivity and substrate specificity experiments were carried out. Placental MAO activity was inhibited by low concentrations of type A inhibitor and was relatively insensitive to those of type B. Simple sigmoidal and identical inhibition curves with various concentrations of either type A or type B inhibitors were obtained with these substrates. These findings suggest that mitochondria MAO in human placenta essentially consists of one distinguishable type of MAO which closely resembles the type A MAO found in other tissues of many species.


[Irritative activity of antiinflammatory agents, betamethasone 17-valerate, beclomethasone 17, 21-dipropionate, betamethasone 17, 21-dipropionate, or indomethacin on the gastrointestinal tract in rats and dogs (author's transl)]. Irritative effects of three steroidal anti-inflammatory drugs on the gastrointestinal tract of rats and dogs were determined. With either single or repeated subcutaneous administration these drugs dose dependently irritated the gastric mucosa of both species. The intestinal mucosa was less affected. Concomitant oral administration of aspirin or subcutaneous administration of indomethacin revealed an aggravation of aspirin-induced gastric ulcers by betamethasone valerate and inhibition of indomethacin-induced intestinal ulcers by beta-methasone dipropionate. These two steroidal drugs had no noxious effect on healing of chronic gastric ulcers induced in rats and dogs. Betamethasone valerate, however, delayed the healing of gastric ulcer in rats. Indomethacin, a non-steroidal anti-inflammatory drug, also induced serious damage to the gastric and intestinal mucosa both of rats and dogs. Indomethacin ingestion delayed the healing of chronic gastric ulcer in rats but not in dogs. Since both steroidal and non-steroidal drugs induce damage to the gastrointestinal tract, a careful monitoring of the patients' complaints should be carried out when these compounds are used as a systemic treatment. Steroidal drugs used in this study, however, appear to be highly safe from the point of dose inasmuch as they are used as a topical treatment.


A new omomyid primate from the Wasatch formation of southern Wyoming. A new omomyid primate, Arapahovius gazini, is represented by many jaws and teeth and a few tarsal bones from a 15-meter stratigraphic interval at the base of the uppermost one-third of the Main Body of the Wasatch Formation, south-central Wyoming, USA. This primate is a conspicuous element in a faunule which lived at about the same time as the fauna of the Lysite Member of the Wind River Formation, estimated to be in the interval 52-50 million years before present. Individuals referable to the new omomyid are chiefly specialized by the intricate corrugation of enamel on the occlusal surfaces of their incisors, premolars and molars and by relatively molariform posterior lower premolars. These specializations may be interpreted as adaptation toward a more herbivorous-frugivorous diet. The tarsal bones referred to Arapahovius suggest that animals in this genus were habitual leapers. This new omomyid bears 'omomyine' and 'anaptomorphine' characters and may have been derived from an earlier Wasatchian (earliest Eocene) 'anaptomorphine' such as Tetonoides pearcei Gazin. Arapahovius seems to have had no phylogenetic successors.


Continual sexual receptivity in the female chimpanzee (Pan troglodytes). Daily observations during a 5-year period showed that the mean frequencies of copulation per day during various sexual states of the female chimpanzee were almost identical, except for during maximum tumescence and lactation. The mean frequency of observed copulation peaked during maximum tumescence and was lowest during lactation.