Relaxation of the lower-oesophageal sphincter during swallowing.

A rapid-pull through technique was used to measure lower oesophageal sphincter pressure before and immediately after swallowing. Often no high pressure zone could be detected after a swallow although sometimes an attenuated pressure profile persisted, associated with weakly developed peristalsis. The persistence of normal sphincter profiles was associated with failure of peristalsis or weak peristaltic pressure waves. Overall, there was a significant drop in mean sphincter pressure after swallowing.


Intestinal transit in rural and urban population of Greece.

Intestinal transit times and daily stool weights were measured in 14 residents of Athens and 22 residents of a small village of Greece. Subjects in rural Greece have significantly shorter transit times (38.4 vs 56.8 hr) and heavier daily stools (172 vs 131 g) than those living in Athens. These findings may be attributable to the more refined diet of the urban Greek population and may explain the different incidence of certain bowel diseases in the urban and rural population of Greece.


Comparison of caerulein and cholecystokinin effects upon enzyme concentrations in duodenal aspirates.

The effect of maximal doses of cholecystokinin and caerulein on lipase and chymotropsin concentrations were compared in large groups of patients with almost equal capacities of bicarbonate secretion. The responsiveness of the pancreas is, as a whole, higher with caerulein than with cholecystokinin, this feature being specially evident in patients with chronic calcifying pancreatitis.


Gastroduodenostomy in dogs with and without parietal cell vagotomy. Effect upon gastric emptying and motility, Heidenhain pouch acid secretion and serum gastrin concentration.

Heidenhain pouch (HP) dogs were studied. After gastroduodenostomy (GD) gastric emptying time was unaffected, but cineradiography showed that the strength of the antral contractions diminished considerably, while the number of peristaltic waves increased. "Circus movements" of the barium meal through the GD to the duodenum and back to the stomach through the pylorus occurred. No significant changes in food-stimulated HP acid secretion or serum gastrin response were observed. After parietal cell vagotomy (PCV) gastric emptying and motility was unaffected, but food-stimulated HP acid secretion and serum gastrin response increased significantly. After addition of a GD to PCV gastric emptying time decreased significantly but similar changes in antral motility occurred as after GD alone. The food-stimulated HP acid secretion and serum gastrin response became significantly reduced. Fasting HP acid secretion and serum gastrin concentration were not significantly altered by any of the surgical procedures.


Exocrine pancreatic insufficiency and primitive malnutrition.

Pancreatic function tests were performed before and after dietary therapy in four patients suffering from primitive malnutrition. Maximal bicarbonate concentrations and lipase activity were the parameters most clearly affected by malnutrition and those showing the fastest recovery following therapy. With reference to this quick recovery it seems unlikely that, at least in Western countries, malnutrition could be a cause of chronic pancreatitis. Interpretation of pancreatic function tests requires an exact knowledge of the nutritional status.


Non-parallel response of amylase and chymotrypsinogen biosynthesis following pancreatic stimulation: a possible explanation for observed non-parallelism in pancreatic secretion.

The response of amylase and chymotrypsinogen to a pancreatic secretory stimulation (intragastric administration of oleic acid or sodium oleate) are compared in rats. This comparison concerned the rates of biosynthesis of the two enzymes, their intrapancreatic levels of storage and their rates of excretion in the juice. In each of these 3 steps, it was found that the stimulation induced non-parallel courses of amylase and chymotrypsinogen. The non-parallelism in the rates of biosynthesis was found unable to explain the entire non-parallelism observed in the rates of excretion. These results suggest that the mechanism which controls the proportions of the different enzymes in the juice is different from that which monitors the rates of individual enzymes biosynthesis.


Duodenal denervation in dogs. Effect upon gastroduodenal emptying and motility, Heidenhain pouch acid secretion and serum gastrin concentration.

In dogs with the continuity of the stomach and duodenum intact the peristaltic and antiperistaltic waves in the duodenum disappeared completely and gastric emptying became faster after selective duodenal denervation. No significant changes occurred in fasting and food-stimulated Heidenhain pouch acid secretion or in serum concentration. It is concluded that the duodenal vagal nerves have importance for duodenal motility, but do not influence the gastrin release from the antrum and the small bowel or the acid secretion from a Heidenhain pouch.


Effect of alcohol on the heme and porphyrin synthesis interaction with phenobarbital and pyrazole.

The effect of alcohol in addition with respectively phenobarbital and pyrazole on the heme porphyrin synthesis in the liver of male rats was studied. After a single dose of 2 g alcohol/kg p.o. the activity of the delta-aminolevulinic acid synthetase (ALA synthetase) in the liver of starving rats increased 2- to 3-fold within 3 h. The porphyrin concentration in the liver of these animals was increased maximally by 75%. The activity of the delta-aminolevulinic acid dehydratase (ALA dehydratase), of the microsomal monoxygenase and of the concentration of cytochrome P-450 and ATP in the liver were not altered. A previous injection of pyrazole (6 mumol/kg) could abolish the inducing effect of alcohol on the ALA synthetase. The inducing effect of alcohol was increased by a previous injection of phenobarbital (80 mg/kg). The activity of the microsomal monoxygenase and the concentration of cytochrome P-450 was not altered by administration of an 8% alcohol solution instead of drinking water. The activity of the ALA synthetase in the liver of these animals was increased 3- to 4-fold only when they starved before sacrifice. In fed animals the activity of this enzyme was in the range of the control animals. The increase of the cytochrome P-450 concentration in the liver after 80 mg phenobarbital sodium/kg was lowered by alcohol. The experiments show that alcohol differs from other known porphyrinogenic agents. An alteration of the cytochrome P-450 concentration could not be demonstrated as the cause of the induction of the ALA synthetase. The observed porphyrinogenic effect is not caused by alcohol itself by either by its metabolites or by the changes of the liver metabolism caused by the effect of alcohol on the NAD/NADH ratio.


Relation between cholic acid synthesis rate and faecal radioisotope excretion following oral administration of 14C-cholic acid.

Bile acid kinetics were evaluated after oral administration of 14C-labelled cholic acid in ten normal subjects and two patients with severe bile acid malabsorption. The faecal 14C excretion was measured during the turnover study. Cholic acid synthesis rate was significantly correlated to 14C output in stools. The faecal radioisotope excretion is recommended for detection and semi-quantitation of bile acid malabsorption.


Somatostatin mode of action on gastric acid secretion in dogs.

The aim of the present study was to investigate the mode of the inhibitory effect of somatostatin on gastric acid secretion. This was done in Heidenhain-pouch dogs studying the effect of somatostatin on cumulative dose response curves of pentagastrin, carbachol and histamine. Somatostatin inhibited gastric secretion after all three stimuli, with decreasing potency against carbachol, pentagastrin and histamine. The pentagastrin-stimulated acid secretion was inhibited in a noncompetitive way; in contrary to this the carbachol and also the histamine-stimulated secretion was inhibited in a competitive way.


Glucagon levels in normal and diabetic subjects: use of a specific immunoabsorbent for glucagon radioimmunoassay.

Non-specific plasma effects may produce major errors in the estimation of true plasma pancreatic glucagon concentrations by radioimmunoassay. This has been circumvented by the production of glucagon-free plasma for each individual investigated, by means of glucagon antibody, coupled to sepharose beads. True fasting pancreatic glucagon levels (mean+/-SEM) in 18 healthy subjects (24+/-3 pg/ml) were significantly lower (p less than .005) than in 10 non-ketotic non-obese diabetics (38+/-3 pg/ml). It is suggested that, in the presence of decreased insulin-effect in the diabetic, this 55% glucagon elevation in diabetics may be of biological importance and contribute to the fasting hyperglycaemia.


HLA-types, C-peptide and insulin antibodies in juvenile diabetes.

HLA-types were determined in 102 juvenile diabetics. HLA-B8 was found in 39 patients (RR 2.64; p less than 0.01) and HLA-BW15 in 32 patients (RR 1.33; n.s.). HLA-B7 was found in 14 patients (RR 0.40; p less than 0;05). There were no correlations between HLA-B8 or BW15 and family history of diabetes, occurrence of infection before onset of diabetes, ketonuria at onset or the age at onset of diabetes. Serum C-peptide, insulin binding capacity of IgG and total serum insulin, IRI, were determined in 94 patients who had had diabetes for more than two years and who were beyond the remission period. Measurable amounts of C-peptide were found in 33 patients (34.7%). There was no evidence of a relationship between any particular HLA-antigen and the B-cell function except for an increased incidence of do a decreased incidence of detectable C-peptide in patients with the combination HLA-B8, W15. Only four patients (4.3%) were lacking insulin antibodies; HLA-BW15 positive patients had higher levels of insulin antibodies than other groups, while HLA-B7 positive patients had lower levels; The results suggest that HLA-B7 and HLA-B18 might be associated with a different and perhaps milder form of juvenile diabetes.


Plasma corticosterone concentrations in diabetic (db) mice.

Plasma corticosterone concentrations in diabetic (db) mice maintained on two different inbred backgrounds were found to be elevated significantly when compared to normal controls. These data are similar to that reported with the phenotypically similar obese (ob) mouse. These results suggest that the hyperadrenolcorticism is not related to the primary gene action of either gene but rather is a consequence of the development of the obesity-diabetes syndromes.


Is a lag-storage curve an early sign of diabetes? Early insulin responses to i.v. glucose in normal subjects, mild maturity-onset diabetics and patients with lag-storage curves.

Early insulin responses were measured after a high dose (50 g/1.73 m2) of rapidly injected glucose in 31 subjects who had repeatedly shown "lag-storage" curves in the OGTT, in 24 controls and in 19 mild maturity-onset diabetics. Division between controls and diabetics was virtually complete, when the insulin responses were expressed as "insulinogenic index" (delta insulin/delta glucose). Twenty out of 31 patients with lag curves showed normal early insulin responses and 11 patients showed diabetic responses. In patients with lag curves, presence of obesity, and absence of family history of diabetes were associated with normal insulin responses. It is concluded that the finding of a lag curve is of little consequence in obese persons but, when in conjunction with a genetic background of diabetes, is suggestive of diabetes.


Glomerular size and structure in diabetes mellitus. II. Late abnormalities.

A study of autopsy kidney material from six long-term diabetics and four controls was performed in order to elucidate the mechanism of the glomerular enlargement in long-term diabetics. The volume and the severity of the glomerular lesions were measured in each of a number of randomly selected, open glomeruli. The relative amount of solid material was taken as an expression of the severity of the glomerular lesion. In the long-term diabetics the volume of open glomeruli was almost doubled compared to that of controls and in the individual subject the enlargement was found to be inversely related to the relative amount of solid material in the glomeruli. This indicates that the enlargement of open glomeruli in long-term diabetics is due to a compensatory hypertrophy rather than to the excessive deposition of basement membrane material. The number of nuclei per open glomerulus was increased in long-term diabetics, but nuclear size was unchanged. Most of the long-term diabetics had a large number of occluded glomeruli and the individual, relative number of such glomeruli correlated closely both with the duration of diabetes above 15 years and the concentration of creatinine in serum. It is concluded that the destruction of glomeruli due to diabetic microangiopathy is compensated for some years by hypertrophy of the least affected glomeruli. This compensatory hypertrophy of glomeruli might well account for the preservation of renal funtion in long-term diabetics for a number of years despite the progressive basement membrane lesions of diabetic microangiopathy.


Effects of exogenous glucagon and epinephrine in physiological amounts on the blood levels of free fatty acids and glycerol in dogs.

Exogenous glucagon or epinephrine were infused into normal overnight fasted dogs to raise circulating hormone levels to concentrations within the physiologic range. Plasma levels of glycerol and free fatty acids remained unchanged during the glucagon infusion, but rose significantly during the administration of epinephrine. Plasma insulin in the systemic circulation remained unchanged during the glucagon infusion and increased slightly during the infusion of thecatecholamine. The data suggest that in normal dogs glucagon in physiological amounts has no lipolytic effect. The importance of the sympathetic nervous system in regulating lipolysis in normal mammals is stressed.


The influence of age on the development of hypertriglyceridaemia and hypercholesterolaemia in genetically diabetic mice.

The effect of spontaneous diabetes on plasma lipids during the natural course of the disease was studied in genetically diabetic mice (C57BL/KsJ-db/db). Hyperlipidaemia developed uniformly in all mice studied and was found to be a characteristic part of the diabetic syndrome, as compared to normal littermates. The hyperlipidaemia was characterized by a marked rise in plasma triglyceride levels with age and severity of the disease increaing from 120+/-6 mg/dl at 5 weeks of age to 400+/-91 mg/dl at 19 weeks of age. In addition, db/db mice were observed to be hypercholesterolaemic as compared to age-matched normal littermates, The plasma cholesterol levels of diabetic mice were elevated early in the disease, as compared to control mice (200+/-6 vs. 130+/-7 mg/dl, respectively), and the mean level remained elevated throughout the period of observation.


Persistent metabolic abnormalities in diabetes in the absence of glucagon.

In order to investigate the contribution of glucagon to the abnormalities of carbohydrate and lipid metabolism in diabetes, hormones and metabolites were measured in response to IV arginine in 5 juvenile onset (control) diabetics and 5 totally pancreatectomised subjects. In the basal state, both control diabetics and pancreatectomised patients showed abnormally elevated levels of plasma glucose, blood 3-hydroxybutyrate, glycerol and plasma free fatty acids (NEFA), although no glucagon was detectable in the plasma of the pancreatectomised subjects. Blood concentrations of the gluconeogenic precursors alanine and glycerol were higher pancreatectomised patients than in the diabetics. Following infusion of arginine, the rise in glucagon observed in the diabetics was accompanied by a significant increase in plasma glucose and a fall in blood lactate when compared to the pancreatectomised subjects. In spite of the rise in glucagon in the control diabetics, no sigficant change was found in the concentrations of ketone bodies, glycerol or NEFA. Thus glucagon does not seem to have a primary role in producing the metabolic abnormalities of diabetes.


Separation of isolated cell nuclei of tissues of the meal moth, Ephestia kuehniella Z. by metrizamide density gradient centrifugation.

The behaviour of isolated cell nuclei of different tissues in the mediterranean meal moth has been studied in metrizamide density gradients to find whether differences exist in the bouyant density between nuclei derived from different specialized tissues. The different nuclei studied have buoyant densities ranging form 1.228-1.295 g/cm3 in metrizamide density gradients and clear differences exist between different populations of nuclei. The different buoyant densities make it possible to separate isolated nuclei from a heterogeneous population of nuclei according to their characteristic densities. This has been tested by the separation of silk gland nuclei from follicle cell nuclei by the density centrifugation method. The degree of polyploidy of the nuclei is not correlated to a decrease or increase of the buoyant density, which suggests that different amounts of nuclear proteins, ribonucleoproteins or RNA are responsible for the differences determined. These tissue-specific differences of the nuclear densities might be correlated to different transcriptional activities. In addition to this, the isopycnic sedimentation technique in metrizamide density gradient provides a method to purify nuclei very carefully without any visible alteration of their morphology and integrity.


Structures indicative of keratinization in lactating cells of bovine mammary gland.

Keratohyalin granule-like aggregates and tangles of filaments similar to epidermal prekeratin fibrils have been observed in lactating cells of bovine mammary epithelium. The concomitant occurence of such structures, which are characteristic of early stages of keratinization, with typical secretory products such as casein micelles demonstrates that keratinization can take place in functional secretory cells. The observations are discussed in relation to current concepts of keratinization in epidermal and in non-epidermal epithelia.


The effect of alpha-amanitin on nucleic acid synthesis in preimplantation mouse embryos.

It has been hypothesized that multiple forms of RNA polymerase may play a role in the control of development and differentiation in eukaryotic organisms. For this to be true, three criteria must be met. First, multiple forms of RNA polymerase must be demonstrated. Second, the relative proportion of the enzyme forms must be shown to change with development or differentiation. And third, the types of RNA synthesized must correlate with the types of RNA polymerase present at each developmental stage. We have previously reported data satisfying the first two criteria for preimplantation mouse embryos. The present paper probes the third criterion in this differentiating system. It was found that although the proportion of the RNA polymerase enzyme forms changes from the 8-cell to the blastocyst stage of development, the types of newly synthesized nucleic acids at each of these stages were similar. Furthermore, inhibition of rRNA, mRNA, and tRNA, by alpha-amanitin, was identical for 8-cell and blastocyst embryos. The only difference between these two stages was that DNA synthesis in blastocysts was more sensitive to inhibition by alpha-amanitin than DNA synthesis in 8-cell embryos. We conclude that the synthesis of different classes of RNA by preimplantation mouse embryos is not simply controlled by changes in the levels of the multiple forms of RNA polymerase.


Ribosomal RNA synthesis in the Eastern North-American Newt, Notophthalmus viridescens.

Ribosomal RNA (rRNA) synthesis, the initiation of which is an early major event during the transformation of iris into lens in the newt, was characterized in the TVI cell-line derived from the eastern North-American newt Notophthalmus viridescens. Employing the technique of polyacrylamide gel electrophoresis, molecular-weight measurements were made on newt rRNAs using Xenopus laevis and E. coli rRNAs as standards. The molecular weights of N. viridescens 28S and 18S rRNA were found to be 1.4 X 10(6) and 0.7 X 10(6) respectively. The precursor to these RNAs had a molecular weight of 3.1 X 10(6). Three probable intermediates in the processing of precursor to mature rRNA were also identified. On the basis of the molecular weights of all species of RNA identified, a processing pathway, similar to that of Xenopus, has been suggested. Some unusual features in the kinetics of precursor rRNA labelling and processing suggest the possibility that newt-cell rRNA synthesis may be controlled by the availability of essential amino acids in a manner similar to that observed in mammalian cells. A possible relationship between the availability of essential amino acids, the initiation of rRNA synthesis in the newt iris, and the control of lens regeneration is discussed.


Direct transhepatic measurement of portal vein pressure using a thin needle. Comparison with wedged hepatic vein pressure.

A technique for the direct measurement of portal vein pressure in fully conscious patients is described. This uses a percutaneous transhepatic approach with a thin Chiba needle and is shown to be simple and safe. The technique has been applied to 123 patients with a variety of liver disorders and the pressure measurements have been compared with those obtained by the indirect technique of wedge hepatic vein catheterization. Close agreement was found between portal vein pressure and wedged hepatic vein pressure in quiescent alcoholic liver disease and alcoholic hepatitis. In chronic active hepatitis, portal vein pressure tended to be higher than wedged hepatic vein pressure, indicating a presinusoidal component to the portal hypertension. This technique is shown to be useful in assessing idiopathic protal hypertension and in demonstrating hepatofugal flow.


Antibody to hepatitis B core antigen in chronic hepatitis and primary biliary cirrhosis: evaluation by a new autologous solid phase radioimmunoassay.

Anti-HBc, the antibody to core antigen of hepatitis B virions, was assayed by a new solid phase sandwich radioimmunoassay inhibition method in the sera of 26 patients with HBsAg-negative chronic active hepatitis (CAH) and 31 patients with primary biliary cirrhosis (PBC). The sensitivity of the method was validated by finding anti-Hb titers averaging greater than 1:1000 in a group of 8 chronically HBsAG-positive individuals, 4 of whom had chronic persistent hepatitis and 4 of whom had no histological or biochemical evidence of liver disease. However, anti-HBc was not detectable in any of the 26 patients with HBsAg-negative CAH. Sera from 2 of the 31 PBC patients contained anti-HBc but only in low titers, a distribution of anti-HBc similar to that found among a comparison group of medical personnel. Anti-HBc testing among PBC patients and control subjects identified a few persons in whom negative tests for HBsAg and anti-HBs failed to identify previous hepatitis B infections. Nevertheless, the uniformly negative tests for anti-HBc among our HBsAg-negative patients with CAH provide additional evidence that this subgroup, typically young-middle age females, seldom derive CAH from hepatitis B infection.


"Nonalcoholic" chronic hepatitis in the alcoholic.

Ten alcoholic patients with biopsy proved chronic active or chronic persistent hepatitis were observed. In each patient, the responsible etiological agent appeared to be ethanol. Laboratory abnormalities could be distinguished statistically from those in a group of 121 patients with alcoholic hepatitis by their higher SGPT (262 +/- 139 versus 62 +/- 7 U per ml, P is less than 0.01), lower ratio of SGOT:SGPT (1.96 +/- 0.34 versus 4.71 +/- 0.40, P is less than 0.01), and lower white blood cell count 5,833 +/- 763 versus 10,370 +/- 742, P is less than 0.01). However, the overlap between the groups was sufficiently large that without histological confirmation the correct diagnosis was in doubt for any given patient.


Dantrolene-associated hepatic injury. Incidence and character.

Hepatic injury during long term dantrolene sodium therapy occurred in 19 of 1044 patients (1.8%) monitored for at least 60 days. Six had icteric hepatitis (0.6%) and 3 died (0.3%). After the marketing of the drug, an additional 31 cases of dantrolene-associated liver disease were available for analysis. Of these 16 had icteric hepatitis with a favorable outcome, whereas 11 died. The injury was mainly hepatocellular with a pattern of acute or subacute hepatic disease or chronic active hepatitis. Analysis of total of 50 cases showed a 28% case fatality rate. All the fatalities occurred in patients above 30 years of age and after at least 2 months of therapy, with 57% cases exposed for at least 6 months. Eleven of the 14 fatalities occurred in females (P is less than 0.05). No cases of hepatic disease occurred in patients exposed for less than 1 month or under the age of 10. The majority of adverse reactions (71%) occurred between 1 and 6 months of therapy. Daily dosage of 300 mg or more is associated with higher incidenceof hepatotoxic reactions and with the majority (85%) of the fatalities. The idiosyncratic hepatic injury does not appear to involve hypersensitivity to the drug. A careful assessment of the benefit-risk ratio in the therapeutic use of dantrolene sodium is proposed.


Protein content of thoracic duct lymph in patients with bilharzial hepatic fibrosis.

The proteins in the thoracic duct lymph were studied in 46 patients with bilharzial hepatic disease in various stages. The thoracic duct proteins were compared to those of serum and ascitic fluid. Total protein and albumin in thoracic duct lymph were 66 and 69% of the concentration of those in the serum of nonascitic patients. The proteins in the thoracic duct lymph were 29% of the serum level in patients with tense ascites. The lymph to serum and ascitic fluid to serum ratios of the total protein and albumin were similar to each other in moderate and severe ascites, reflecting a low protein content in both the ascitic fluid and thoracic duct lymph. The gamma-globulin concentration was raised in the serum of all patients as well as in the ascitic fluid of those with tense ascites. A contrasting pattern of the proteins is present in the thoracic duct lymph in bilharzial hepatic fibrosis. In the early stages the lymph has a relatively high concentration of protein, which decreases as the disease advances.


Intrahepatic branching patterns of portal vein. A study by corrosion cast.

Eighty-five corrosion casts of human portal veins were studied. The following observations were made: (1) In 88% of the cases, the portal vein divided into right and left branches, and in 12% of the cases, it divided into the left branch of the portal vein and anterior and posterior segmental n:veins; (2) Anterior and posterior segmental veins were branches of the right branch of the portal vein in 88% of the cases and arose directly from the portal trunk in 12% of the cases. In all cases, the anterior and posterior segmental veins in turn divided into superior and inferior area veins. (3) The left branch of the portal vein underwent a sharp kink leading into two parts: pars transversa nad pars umbilicalis. (4) The lateral superior area vein either sprang from the left side of the kink (69%), or from pars transversa near the kink (16%), or from the left side of pars umbilicalis near the kink (14%). The lateral inferior area vein arose from the left side of pars umbilicalis in all cases. (5) The medical segmental veins originated from the right side of pars umbilicalis. The number of branches varied from two to four. Further division of these into area branches were not fixed. (6) The right portion of the caudate lobe received portal blood either from the pars transversa (68%), or from the right branch of portal trunk (14%), or from the portal trunk (18%). The left portion of the caudate lobe received portal blood always from the pars transversa of the left trunk. (7) The branches to the caudate process arose from right branch of the portal vein in the majority of cases (72%). In the rest of the cases, these arose either from portal trunk (16% cases) or from pars transversa of the left trunk (12% cases).


Factors affecting bilirubin excretion in patients with cholesterol or pigment gallstones.

To identify factors affecting bilirubin excretion, the effects of bile flow and bile salt excretion on bilirubin output into bile have been examined in normobilirubinemic, cholecystectomized patients with balloon-occludable, reinfusion T-tubes, 8 patients with cholesterol (CS) and 2 with pigment (PS) gallstones. Another patient with pigment gallstones, sickle cell disease (SS), and stable jaundice was studied to examine the mechanism by which an increased bilirubin load was excreted. Total bilirubin was almost entirely conjugated and excretion was related linearly to bile salt excretion PS and CS subjects; one-third of bilirubin excretion was bile salt independent and two-thirds was bile salt associated. In the SS patient 90% of the bilirubin excretion was independent of bile salt output. In PS and CS patients, bilirubin output was linearly related to bile flow, but the SS patient showed significant bilirubin excretion at low flow rates. CS and PS patients had similar patterns of bilirubin excretion, but the increased bilirubin load in the SS patient was excreted independently of bile salts. In the SS patient, unconjugated bilirubin output was hyperbolically related to bile salts output and represented a maximum of 3% of the total bilirubin output. The bile salt-independent excretion of conjugated bilirubin suggests that micelles were not required for transport into bile; whereas the hyperbolic relationship for unconjugated bilirubin and bile salt output, similar to that of the micellar lipids. cholesterol, and phospholipids, suggests interaction with micelles.


An experimental method for studying in vivo gallbladder absorption.

A perfusion technique has been developed for the study of net absorption in the gallbaldder of the cat. The lumen of the gallbladder in situ with intact blood vessels and nerves is perfused at a constant rate with bile or a solution of known composition. Differences in volume input and output from the gallbladder are measured with a volume transducer, which in the absence of changes in gallbladder volume reflects net water absorption. By adding polyethylene glycol to the perfusate, net water absorption rate can be calculated from the changes in concentration of this test substance regardless of gallbladder motility. A combined use of these two methods makes possible a concomitant estimation of net water absorption and changes in gallbladder volume. The technique was tested and used for the study of net water absorption from bile, saline and isotonic mannitol solution in the gallbladder lumen.


Effects of intravenous secretin and cholecystokinin on gallbladder net water absorption and motility in the cat.

A perfusion technique has been used for the simultaneous study of the concentrating mechanism and the motility of the gallbladder in the anesthetized cat. It was found that intravenous secretin abolished the net water absorption from bile in the gallbladder and thereby impeded its concentrating mechanism, but alone did not influence gallbladder motility. It was sometimes seen that secretin even reversed the net water transport in the gallbladder, producing a secretion. Intravenous cholecystokinin was found not to influence the net water transport but to induce a strong contraction of the gallbladder. These results are discussed in relation to those from earlier in vitro studies.


Fiberoptic pansigmoidoscopy. An evaluation and comparison with rigid sigmoidoscopy.

A flexible 60-cm fiberoptic sigmoidoscope was evaluated in 139 patients. In 120 patients flexible sigmoidoscopy was compared with routine rigid sigmoidoscopy with respect to patient tolerance, distance of inspection, procedure time, and diagnostic yield. All patients were prepared with a single cleansing enema, and given no analgesia. Despite the fact that the flexible instrument was inserted nearly 3 times as far into the colon (55 cm versus 20 cm), more patients preferred the flexible examination. Significant pathological lesions were discovered by the flexible examination in 39% of patients, whereas rigid sigmoidoscopy discovered lesions in only 13%. Fluoroscopy performed during flexible sigmoidoscopy in 19 additional patients revealed that the instrument tip had reached the descending colon or beyond in 84% of patients. There were no complications. The flexible fiberoptic pansigmoidoscope offers promise as a practical diagnostic tool for a rapid and complete examination in patients with suspected colorectal diseases.


Minimal bile acid malabsorption and normal bile acid breath tests in cystic fibrosis and acquired pancreatic insufficiency.

This study was undertaken because of reports of a marked increase in fecal bile acid excretion by children with cystic fibrosis. We attempted to confirm this finding by performing [1-14C]cholylglycine breath tests and by measuring fecal bile acid and fat excretion in patients with cystic fibrosis and acquired pancreatic insufficiency. Studies were done when patients were taking pancreatic enzymes (Cotazym) and also without medication. 14CO2 excretion in breath was normal in patients with acquired pancreatic insufficiency and even lower in cystic fibrosis, both with and without Cotazym therapy. Fecal bile acid excretion was slightly elevated in both groups without Cotazym and became normal with Cotazym in patients with acquired pancreatic insufficiency. Steatorrhea was present in both patient groups and improved during Cotazym therapy. Bile acid malabsorption in cystic fibrosis and acquired pancreatic insufficiency is minimal and probably not clinically important.


Regnerative of cardiac type mucosa and acquisition of Barrett mucosa after esophagogastrostomy.

The surgically created squamocolumnar junction in patients who have undergone an esophagogastrostomy after partial esophagogastrectomy provides a unique opportunity to study mucosal regeneration in the setting of gastroesophageal reflux. The pathological and clinical findings in 17 such patients are presented. In each patient the anastomosis had been performed between histologically documented squamous-lined esophagus and gastric fundus. Cardiac type mucosa had regenerated in the region of the anastomosis in 9 patients and was detected as early as 2 months after operation. In addition, 3 patients, 2 of whom had cardiac type mucosa, had acquired Barrett or Barrett-like mucosa on the distal esophagus by 76 to 119 months. Gastroesophageal reflux was prominent in all 3 of these patients. The findings strongly support the hypothesis that the distinctive mucosa of Barrett's esophagus develops after reflux-induced ulceration and subsequent mucosal regeneration by immature cells that are derived from cardiac and/or fundic mucosa, and which undergo specialized differentiation in the presence of reflux.


Symptomatic intestinal disaccharidase deficiency in alcoholics.

Lactase and sucrase activities were measured in jejunal biopsies from a group of alcoholic and nonalcoholic men of similar nutritional status, consisting of American blacks, and whites of northern European origin. When measured withing 10 days of alcohol withdrawal, sucrase activity was decreased by 33% in the alcoholics. Lactase activity was less than 1 U per g in 100% of the black and 20% of the white alcholics as compared to 50% of the black and none of the white control subjects. Lactase activity was virtually absent in 45% of the black alcoholics. A second jejunal biopsy after an additional 2-week period of alcohol abstinenece exhibited significant secondary increases in the activities of both disaccharidases. Oral administration of lactose (1 g per kg of body weight) resulted in significantly lower blood glucose concentration and higher incidence of adverse effects in alcoholics, mainly among the blacks. Although data from larger populations are needed to confirm our observations, these findings suggest that chronic alcohol ingestion decreases intestinal disaccharidase activities even in the absence of overt malnutrition. The decrease in enzyme activity produced by alcohol is associated with increased morbidity after lactose administration.


Effect of protonated 2,4,6-triaminopyrimidine, a tight junction blocker, on intestinal transport in dog ileum in vivo.

Previous in vitro experiments suggest that protonated 2,4,6-triaminopyrimidine (TAP+) inhibits passive Na+ movement across tight junctions of various epithelial tissues. So far no evidence has been found that TAP+ interferes with other mucosal transport processes. Because blockage of the tight junctions would be a promising tool in studying intestinal transport physiology, the effect of TAP+ was investigated in the dog ileum in vivo. When TAP+ was added to a sodium-free mannitol solution, the transepithelial sodium diffusion potential was significantly decreased (60% inhibition with 34 mm TAP+); this would be expected if TAP+ inhibited NA+ permeation through tight junctions. However, TAP+ was also found to diminish Na+ and Cl- absorption. Furthermore, TAP+ increased unidirectional Na+ flux from plasma to lumen; this is opposite to the expected result of tight junction blockage. In addition, TAP+ reduced glucose, fructose, and xylose absorption by about 50%. In ileal loops exposed to cholera toxin, TAP+ enhanced secretion by a rate equal to the rate by which it reduced absorption in loops not exposed to cholera toxin. All changes induced by TAP+ approached normal within 4 hr of its removal from the perfusate. TAP+ did not cause nay mucosal damage that could be detected by protein leakage or by light microscopy. These studies show that TAP+ has many effects on intestinal transport processes that cannot be explained on the basis of tight junction blockage.


Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed.

Thirty days after resection of 10 to 80% of the midportion of the small intestine, excluding the duodenum, several cell kinetic parameters were investigated in the residual intestine. The degree of intestinal response increased in a stepwise fashion as the amount of tissue removed was increased. The response involved marked increases in: DNA synthesis per crypt expressed as disintegrations per minute of tritium (3H) reflecting (3H)thymidine incorporation, cells per crypt column, 3H-labelled cells per crypt column, cells per villus column, and thickness of all intestinal wall components. These changes occureed throughout the small intestine even at lesser resections. ""Crypt profiles'' reflected changes in cell counts, but when the labeling frequency of proliferative cells was expressed as a percentage of the total crypt height, there was no change. The total number of crypts in the duodenum remained unchanged and the total number of cyrpts in the residual jejunum plus ileum decreased proportionally to the amount of tissue removed. Intestinal compensation occurred by increasing the size of the structures present in the residual intestine, not by increasing the number of structural units.


Compensation by the residual intestine after intestinal resection in the rat. II. Influence of postoperative time interval.

The sequence of events which comprise the early response of the residual intestine to 70% resection of the combined jejunum and ileum was investigated. Animals were killed at 2,4,6,8, and 12 postoperative days. Marked increases in DNA synthesis expressed as disintegraions per minute per crypt, cells per cyrypt column, labeled cells per crypt column, thickness of intestinal wall components, and cells per villus column were apparent as early as 2 to 4 postoperative days. By 12 days, the values had reached the 30-day postoperative levels found in earlier experiments, indicating that a new steady state had already been reached. Jejunal and ileal crypts responded nearly the same during the first 12 days with their sizes increasing to about 150% of control values. However, although jejunal villus cell counts increased to 125% of controls, the ileal villus cell counts  increased to 180% of controls, indicating that the sizes of the two crypt and villus epithelial cell populations are independently controlled.


Direct and indirect effects of dextrose and amino acids on gut mass.

Oral intake of an elemental diet maintains small intestinal mucosal mass compared to the atrophy seen after intravenous infusion of the same diet. The greatest difference in intestinal mass occurs in the proximal bowel and is thought to occur because of rapid absorption in the proximal small bowel. This study was designed to determine the effects of the individual components of the elemental diet and their site of administration within the small bowel on small intestinal mass. Rats were maintained on intravenous alimentation and the proximal gut (by intragastric infusion) or the ileum was continuously infused with equal volumes of 30% dextrose, 5% dextrose, 5% amino acids, saline, or 30% mannitol. After 1 week of combined intravenous alimentation and gut infusion, the rats were killed and parameters of small intestinal epithelial mass were determined sequentially for the entire bowel. Although saline- and mannitol-infused controls did not differ from uninfused intravenously fed rats, proximal infusion of 30% dextrose reproduced the effects of a complete elemental diet. Proximal infusion of amino acids but not 5% dextrose had a limited effect on the duodenum and jejunum. Ileal infusion of 30% dextrose led to local hyperplasia of the site of infusion and in addition produced hyperplasia of the proximal gut. Ileal amino acid infusion, but not 5% dextrose infusion, led to local ileal hyperplasia. We conclude that: (1) intraluminal dextrose and amino acids have direct effects in maintaining gut mass (2) the gut is more responsive to amino acids compared to 5% dextrose, and (3) ileal 30% dextrose infusion leads to remote effects in the proximal gut, perhaps mediated by hormonal or neurovascular factors.


Effects of catecholamines and their inhibitors on the isolated canine pancreas. I. Noradrenaline and isoprenaline.

alpha Adrenergic agonist (noradrenaline, 2, 20, and 200 mug) and antagonist (phenoxybenzamine, 15 mg), and beta adrenergic agonist (isoproterenol, 2, 20, and 200 mug), and antagonist (propranolol, 6 mg), were tested on isolated perfused canine pancreas under basal conditions, and under stimulation by a background of secretin (0.5 clinical unit per hr), or of caerulein (600 to 1200 ng per hr). Noradrenaline induced a strong vasoconstriction (inhibited by phenoxybenzamine), followed by a moderate vasodilation (possibly mechanical). Noradrenaline did not stimulate a resting pancreas and inhibited a pancreas from secreting in response to secretin or caerulein. After phenoxybenzamine, in the absence of vasoconstriction, this latter effect was reversed into a dose-dependent stimulation of hydrelatic secretion, suggesting that noradrenaline had a direct action on the secretory cell. There was no stimulation of protein and no acinar degranulation. Propranolol and atropine did not modify the effectiveness of noradrenaline. Isoprenaline had a weak vasodilatory effect but no effect on the secretion. Adrenergic blocking agents did not alter the response to secretin or caerulein.


Effects of catecholamines and their inhibitors on the isolated canine pancreas. II. Dopamine.

Dopaminergic agonists (dopamine, 2, 10, 50, and 250 mug; apomorphine, 1 mg; noradrenaline, 2, 20, and 200 mug), and inhibitors (haloperidol, 5 mg; pentamethonium, 500 mg; phenoxybenzamine, 15 mg, and atropine sulfate, 10 mg), were tested on isolated perfused canine pancreas; under basal conditions and under stimulation by a background of secretin (0.1, 0.5, and 10.0 clinical unit per hr), or of caerulein (1200 ng per hr). Low doses of dopamine induced a vasodilation inhibited by haloperidol Large doses induced a vasoconstriction, presumably by stimulation of alpha adrenergic receptors. Dopamine stimulated hydrelatic secretion. The calculated maximal response was about one-half that of secretin. This response was inhibited by haloperidol but not by atropine, pentamethonium, and phenoxybenzamine. No acinar degranulation was observed after stimulation by dopamine. The response to secretin was not altered by haloperidol. It was concluded that blood vessels and pancreatic tissue contain specific receptors to dopamine different from secretin receptors. Secretory response to noradrenaline after phenoxy benzamine was inhibited by haloperidol, suggesting that this effect was mediated by the stimulation of dopamine receptors of the cells. A hypothetical representation of the interrelation between dopamine, secretin, and noradrenaline is discussed.


Salicylate hepatitis.

Two patients developed acute hepatic injury as a result of salicylate therapy. In each patient serum salicylate levels were below 25 mg per 100 ml during the development of hepatic dysfunction. Liver biopsies, obtained a few days after the peak abnormalities in serum transaminases, revealed nonspecific acute hepatitis. Normal liver tissue was found before the beginning of salicylate treatment in 1 patient, who had systemic lupus erythematosus and drug rechallenge was not attempted. In the other patient, who had rheumatoid arthritis, rechallenge with salicylate evoked hepatic dysfunction and recurrent symptoms. Salicylate-induced liver injury should be considered in the differential diagnosis of hepatic disease occurring in patients receiving high dose salicylate therapy, regardless of serum salicylate levels.


Celiac sprue and Crohn's disease: an association causing severe growth retardation.

Celiac sprue and Crohn's disease have very rarely been documented in the same patient. We report a case involving an adolescent male with known Crohn's disease who had extreme wasting, growth retardation, intractable diarrhea, and delay in development of secondary sexual characteristics. Peroral jejunal biopsy showed a nonspecific flat mucosal lesion compatible with celiac sprue. An 8.0-kg weight increase occurred within 4 weeks of institution of a gluten-free diet. Jejunal rebiopsy documented significant improvement with a mild to moderate villous abnormality. After 2 years on a gluten-free diet, a rebiopsy of the jejunum documented only a mild villous abnormality.


Meconium ileus equivalent complicating cystic fibrosis in postneonatal children and young adults. Report of 12 cases.

Twelve patients with meconium ileus equivalent complicating cystic fibrosis in the postneonatal period were seen at the Mayo Clinic in the years 1950 through 1975. In a child or young adult with known or suspected cystic fibrosis, the triad of recurrent colicky abdominal pain, a mass in the right lower quadrant, and mechanical intestinal obstruction provides a clue to diagnosis of meconium ileus equivalent. The clinical suspicion of meconium ileus equivalent may be confirmed by meglumine diatrizoate (Gastrografin) enema, which in most uncomplicated cases also serves as treatment.


New aspects of the trophic action of gastrointestinal hormones.

This paper deals with several new findings regarding the trophic action of gastrointestinal hormones. Naturally occurring gastrins (G-17 I, G-17 II, G-34 II) stimulated DNA synthesis and increased total DNA content of gastric mucosa. These were several times more potent than pentagastrin on a molar basis. In a survey of various tissues from the gastrointestinal tract, pentagastrin exerted trophic effects on mucosa of the oxyntic gland area, duodenum, and colon; it had no effect on the esophagus, antrum, or diaphragm. Maximal stimulation (200% of control) of colonic DNA synthesis was produced by 250 mug of pentagastrin per kg. Vasoactive intestinal peptide did not stimulate DNA synthesis when given alone and inhibited the trophic effect of pentagastrin when administered simultaneously. Glucagon stimulated DNA synthesis in both colon and oxyntic gland mucosa to 40% of the increase caused by pentagastrin and did not inhibit the effects of pentagastrin when administered concurrently.


Chemical and biological properties of porcine secretin and secretin analogues modified in positions 3 and 4.

The synthesis of secretin does not offer fundamental difficulties any longer. The problem of the stability of the hormone seems to be solved from a practical point of view. However, the mechanism of the inactivation of secretin in solution is not yet satisfactorily explained, alpha-beta Rearrangement of the Asp-Gly bond may play a role, but some observations indicate that inactivation is not a straight reaction. Like secretion [Ala-4] secretin shows beta-sympathomimetic activity. The availability of a suitable depot preparation permits physiological studies with secretin and its analogues after subcutaneous administration.


The role of some polar amino acid residues in secretin.

Three analogues of S5-27, the tricosapeptide with the carboxyl-terminal sequence of secretin, were studied. In the analogues, the acidic residues at positions 9 and 15 of S5-27 were replaced by the neutral residues glutamine and asparagine. These changes resulted in a decrease in immunoreactivity. Binding to an antibody against secretin could be correlated with the changes in the conformation of the synthetic analogues.


Immunological aspects of secretin, substance P, and VIP.

Secretin, substance P, and vasoactive intestinal peptide (VIP) were studied from the immunological point of view using synthetic hormones and their related peptides which were prepared by the conventional method for peptide synthesis. Immunological properties of these hormones were characterized by radioimmunoassays specific to the respective hormones. Antisecretin antisera (NCC-R-1 and R-801) were generated in rabbits with synthetic porcine secretin absorbed on polyvinylpyrrolidone. Antiserum to substance P (R-400) was produced in a rabbit with synthetic substance P-human alpha-globulin conjugate. Generation of anti-VIP antiserum (R-502) was carried out by immunizing rabbits with synthetic VIP absorbed on polyvinylpyrrolidone. Synthetic polypeptides related to the three hormones that were examined in this study include secretin(4-27), secretin(5-27), secretin(7-27), secretin(11-27), secretin(14-27), secretin(18-27), secretin(1-22)amide, secretin(7-22)amide, Nalpha-tyrosyl-secretin, [1-Tyr]secretin, [4-Ala]secretin, [4-D-Ala]secretin, [4-Ala,5-Val]secretin, [6-Tyr]secretin, substance P(2-11), substance P (3-11), substance P(4-11), substance P(5-11), substance P(6-11), Nalpha-tyrosyl-substance P, [1-Tyr]substance P, [8-Tyr]substance P, [11-Leu]substance P, des-11-Met-substance P, VIP(7-28), VIP(11-28), VIP(18-28), VIP(1-18)amide, and VIP(1-22)AMIDE. The results revealed two antigenic regions at the amino- and carboxylterminal portions of the secretin and VIP molecules. As to substance P, the major antigenic region was located within the 3 to 11 sequence. The proline residue in position 4 and methionine in position 11 seemed to be of special importance. The immunoassays demonstrated the existence of immunoreactivities of these hormones in hot water extracts from various porcine tissues. In the pituitary, VIP and substance P immunoreactivities were detected, whereas secretin was not. Secretin, VIP, and substance P were found in the pancreas, but at low concentrations. Distributions of these hormones in various sites of the gastrointestinal tract were also demonstrated.


[Ancillary chemotherapy in the primary treatment of carcinoma of the breast. On the growth pattern of carcinoma of the breast and the establishment of a new concept in treatment (author's transl)].

A prospective study of 25 cases of primary carcinoma of the breast was established. The patients were treated by radical mastectomy and lymphadenectomy followed by chemotherapy with Vincristin, Adriblastin and Endoxan. No radiotherapy was employed. During a 12 month follow-up, no patient, had recurrence or progression of the tumor. It is too early to evaluate the treatment definitively regarding survival and definite value of the method. The theoretical and experimental considerations for ancillary chemotherapy are discussed.


[Psychological and sexual acceptance of vaginal hysterectomy for sterilization (author's transl)].

Psychological and sexual sequelae of hysterectomy were studied in 1007 cases between 1 1/2 and 8 years following the operation. Younger women had more often vaginal and older women more ofter abdominal hysterectomies. 78% of the patients thought they had been fully informed about the operation. 4.1% of the patients regretted the hysterectomy. 8% of the patients regretted the loss of menstruation. Most of these did not think they were fully informed. Full information on the type of operation can reduce negative postoperative sequelae. As many patients gained as lost weight following the hysterectomy. Postoperative coital difference did not show any relationship to the type of hysterectomy. In 57% of the cases, improvement occured one year later and in 10% of the cases improvement occurred 2 years later. Sexual relationships were not adversely affected by hysterectomy. Deterioration of the sexual relationship regarding libido and frequency of orgasms was a more frequent complaint in the control group. Improvement of libido and frequency of organsms can still occur 2 years following hysterectomy. Covert and overt depression was as frequent in the hysterectomized group as in the control group. The adverse effects of sterilization by tubal ligation were identical to those found in our group of hysterectomies according to the literature. Therefore we prefer vaginal hysterectomy for voluntary sterilization to tubal ligation.


[Extreme oedema of the ovaries: a contribution to conservative surgery for ovarian "tumours" (author's transl)].

A laparotomy for a suspected cystic ovarian tumour which was thought to extent as far as the costal arch, was carried out on a 24-year-old patient with a long history of oligomenorrhea and sterility. Due to excessive oedema, both ovaries were tremendously enlarged. The right ovary was twisted 360 degrees. No haemorrhagic infarct, however, was present. Both ovaries, which were about 40% of the normal size due to pressure from the oedema, were incized. The ovaries were than sutured and left in situ. Laparoscopy 9 weeks later confirmed that the ovaries had returned to a normal size. The patient's menstrual cycle became regular. Even though the process may be unusually extensive, conservative methods should be given preference when the patient is so young.


[Combined therapy of ovarian cancer (author's transl].

Following the introduction of massive triple drug therapy with high doses of Endoxan, Proresid and Methotrexat instead of the earlier long-term Endoxan treatment in addition of surgery, percutaneous irradiation and intraperitoneal radio-gold, 3 year survival of advanced stages IIb-IV of ovarian carcinoma rose from 19.6% to 42.6%. The 3 year survival of all malignant ovarian tumors (primary or secondary) rose from 38.3% to 51.0%. Further development led to targeted multiple drug therapy (ultrahigh Endoxan, Proresid/VM26, Methotrexat and Adriblastin) according to oncobiogram. The main side-effects, their control and experience with combined chemotherapy and irradiation are described.


[Increasing individualization of the treatment of carcinoma of the endometrium (author's transl)].

Metrium seen from 1969 to 1973 are reported. These results were compared to the results of treatment of carcinoma of the endometrium at the same institution between 1944 and 1960. There was a considerable increase of the mean age of the patients. Consequently the operability was reduced to 74.3%. The necessity to resort to primary radiotherapy rose to 25.7%. Diseases of old age were contra-indications to operative treatment. In cases generally fit for operation the contra-indications to vaginal surgery increased. Vaginal hysterectomy was therefore only employed in 78.5% of the operations. An individualization of the treatment of carcinoma of the endometrium is recommended. Continually good or improved results of the treatment are expected by individualization in the group of patients which already showed impaired health by age or concomittant diseases.


[Prophylactic procedures to prevent respiratory distress syndrome in prematures (author's transl)].

A controlled trial of antepartum glucocorticoid treatment for prevention of Respiratory Distress Syndrome (RDS) or Hyaline Membrane Syndrome (HMS) was carried out. 91 mothers, in whom premature delivery threatened between 27 and 37 weeks of gestation, were given intramuscular injections of 8-12 mg of betamethasone as well as medication inhibiting uterine activity (tocolytica and sedation) and strict bedrest to delay premature delivery for at least 24 to 48 hours. A control group of 118 mothers, who were hospitalized late and premature delivery could not be delayed, had no betamethasone treatment. There was no significant differerence in the incidence of Respiratory Distress Syndrome in premature infants in both groups, but there was a 50% lower mortality rate of Respiratory Distress Syndrome in the betamethasone treated group, due to a milder course of Respiratory Distress Syndrome Disease. Harmful effects from corticosteroids given to pregnant women prior to premature delivery were not observed in our group. The prophylactic treatment with betamethasone to diminish the mortality rate of Respiratory Distress Syndrome is therefore considered encouraging and profitable.


[Lymphografy--a meaningful diagnostic method for classification of gynaecological tumours (author's transl)].

The data about the significance of lymphografy vary between 50% and 90%. The histological findings of the lymphnodes by patients with carcinoma of the cervix uteri operated according to the method of Wertheim-Meigs showed that the findings of lymphografy agree in 68% of the cases with the histological ones. An agreement of lymphografy and histological diagnosis however had been demonstrated in 84% of the cases when there was more than a suspect praetherapeutic lymphografical finding. Although the indication of lymphografy as a searching method is reasonably doubtful in early cancer cases this possibility of an exact verification of the extension of the tumour should not be neglected. An exact praetherapeutic exploration about the consistance of the lymphonodes is of great importance of an optimal therapeutic effect. The presented data show that the lymphografy should be applicated by patients with gynaecological carcinoma if there is no contraindication.


[The activity of L-cysteine aminopeptidase (Oxytocinase) during premature labour and tocolytic treatment (author's transl)].

The normal levels of L-Cysteine aminopeptidase in the maternal serum from 20 to 41 weeks gestation were tested in 240 samples of serum. The normal levels rise from 0.82 mU/ml at 24 weeks to 4.63 mU/ml at term. In 14 patients with premature labour the enzyme levels were tested during the treatment to inhibit labour with fenotero-hydrobromide. There was no decrease of oxytocinase as a cause of the onset of premature labour. During treatment to inhibit labour the L-Cysteine aminopeptidase showed no deviatiameter of placental function even in patients undergoing treatment to inhibit premature labour.


[Venous flow studies by ultrasound prior and following vaginal hysterectomy (author's transl)].

The flow in the femoral veins was studied by systematic ultrasound examinations in 100 patients before and after vaginal hysterectomies. The following observations were made: 1. In the diagnosis of thrombosis the Valsalyamaneuver is important and preferable to an evaluation of the spontaneous flow with deeprespirations. 2. Postoperatively slight deterioration of the function of the walls of the veins and a slight increase in venous stasis due to impeded venous return is found. 3. The Doppler ultrasound examination does not appear to be efficient enough for routine use. 4. In cases with a history of thrombosis or clinical suspicion of thrombosis the Doppler examination should be used with a specific diagnostic question in mind. In these cases the diagnostic gap between clinical examination and phlebography can be closed by the Doppler examination.


[Submucous lipoma of the uterus (author's transl)].

A case of submucous lipoma of the uterus is described. The suspected location in the curettings was confirmed in the hysterectomy specimen.


Patterns of molecular variation. II. associations of electrophoretic mobility and larval substrate within species of the Drosophila mulleri complex.

Electromorphic variation among populations of Drosophila mojavensis, D. arizonensis and D. longicornis was examined for seven genetic loci. The average electrophoretic mobility for a population was used as the metric. D. mojavensis and D. arizonensis use larval substrates in different parts of their geographic ranges, while D. longicornis is more narrowly restricted to different species of the cactus Opuntia in different localities. There is marked electromorphic variation among populations of either D. mojavensis of D. arizonensis, and the bulk of this variation is accounted for by differences in laval substrate. There is somewhat less variation among populations of D. longicornis, and only a moderate portion of this is accounted for by larval substrate differences. There appears to be an association between the taxonomic diversity of the larval substrates and the electromorphic diversity of the Drosophila populations utilizing those substrates. Evidence is reviewed that suggests physiological mechanisms for these possibly adaptive associations.


Regions of stable equilibria for models of differential selection in the two sexes under random mating.

The equilibrium structure of models of differential selection in the sexes is investigated. It is shown that opposing additive selection leads to stable polymorphic equilibria for only a restricted set of selection intensities, and that for weak selection intensities must be of approximately the same magnitude in the sexes. General models of opposing directional selection, with arbitrary dominance, are investigated by considering simultaneously the stability properties of the trivial equilibria and the curve along which multiple roots appear. Numerical calculations lead us to infer that the average degree of dominance determines the equilibrium characteristics of models of opposing selection. It appears that if the favored alleles are, on the average, recessive, there may be multiple polymorphic equilibria, whereas only a single polymorphic equilibrium can occur when the favored alleles are, on the average, dominant. The principle that the average degree of dominance controls equilibrium behavior is then extended to models allowing directional selection in one sex with overdominance in the other sex, by showing that polymorphism is maintained if and only if the average fitness in heterozygotes exceeds one.


The nature of quantitative genetic variation in Drosophila. III. Mechanism of dosage compensation for sex-linked abdominal bristle polygenes.

Seventeen lines, each homozygous for a different X chromosome but all with a common autosomal genetic blackground, were constructed and assayed for abdominal bristle number to determine whether dosage compensation operates for sex-linked genes affecting this character. --The regression coefficient of male mean on female mean using a logarithmic scale was 0.90 +/- 0.13 and the genetic regression coefficient 0.92, neither differing significantly from unity. The genetic components of variance in males and females were also very similar (0.000234 or 0.000228, respectively). These results indicate that dosage compensation is complete (or nearly so) for sex-linked genes affecting this character. The bristle scores of females did not differ in reciprocal crosses between these lines, thus dosage compensation does not operate by paternal X inactivation. --The question of an adequate scale for abdominal bristle number had to be examined during the study. A logarithmic scale appeared to be adequate for both genotypic and environmental differences.


Delayed formation of chromosome aberrations in mouse pachytene spermatocytes treated with triethylenemelamine (TEM).

Induction of chromosome aberrations in pachytene spermatocytes of mice by 2 mg/kg TEM was compared with induction by 400 R X rays. These doses induced comparably high dominant lethal effects in pachytene spermatocytes of mice. Cytological analysis at diakinesis-metaphase I stage showed that whereas 76.4% of the cells treated with X rays at pachytene stage had aberrations, the frequencies observed in two TEM experiments were only 0.8 and 2.2%. On the other hand, 5% of the progeny from TEM-treated pachytene spermatocytes were found to be translocation heterozygotes. This is the first report on the recovery of heritable translocations from treated spermatocytes of mice. The aberration frequencies observed for TEM in diakinesis-metaphase I were much too low to account for all the lethal mutations and heritable translocations. Thus, the formation of the bulk of aberrations induced by TEM in pachytene spermatocytes was delayed--a marked contrast to the more immediate formation of X-ray-induced aberrations. It is postulated that the formation of the bulk of TEM-induced aberrations in pachytene spermatocytes and in certain postmeiotic stages occurs sometime during spermiogenesis, and not through the operation of postfertilization pronuclear DNA synthesis.


Linkage of genetic determinants for mouse beta-galactosidase electrophoresis and activity.

An electrophoretic polymorphism for beta-galactosidase has been identified among common inbred strains of mice. It is inherited as a single Mendelian factor with two alleles showing codominant expression. This structural gene, Bge, is closely linked (0/163 recombinants) with the Bgs site on chromosome 9 which regulates systemic levels of beta-galactosidase. The distribution of electrophoretic and activity phenotypes among inbred strains is not concordant, indicating that they result from separate mutations. Three aspects of beta-galactosidase realization, its structure, systemic regulation and developmental program, are now known to be organized in close proximity on chromosome 9. Considered in conjuction with evidence from other mammalian systems, this suggests that the mammalian genome, like Drosophila, is organized into large functional units in which relevant regulatory and developmental information is closely associated with individual structural genes.


Chromosomal polymorphisms of constitutive heterochromatin and inversions in Drosophila.

A simple technique for preparing mitotic metaphases from a larval ganglion of Drosophila is described. Parallel examination of polytene and metaphase chromosome groups shows that inversion polymorphism in chromosome 3 of D. recticilia from East Maui (Hawaii) manifests a one-to-one correlation with a metaphase karyotype polymorphism due to the presence of an extra heterochromatic portion. These observations are consistent with the previous findings on other species of Hawaiian Drosophila. They strongly support the hypothesis that when one breakpoint of a long inverted segment of a chromosome element occurs in the vicinity of the constitutive heterochromatin, it may exert an effect in eliciting the production of heterochromatic material in the same chromosome.


The population genetics of sperm displacement.

This article reports the results of some sperm displacement experiments, as well as the results of a theoretical study of selection arising from genetic differences in displacing ability. The experimental work involved the use of three genetic marker stocks in double and triple matings. The speed of displacement following the matings was determined by scoring the progeny of each female daily. There were clear differences between strains in their displacing ability. It is shown how new information concerning the displacement process results when three markers are used; however, no new light is shed by these experiments on the mechanism of displacement. The theoretical study of selection resulting from displacement uses a one-locus, two-allele model in which three diploid male genotypes confer different displacing abilities. The results indicate stable equilibria if (1) there is heterosis, and (2) there are certain nontransitive relationships in displacing ability among the different kinds of double matings. Some evolutionary consequences are discussed in which sperm displacement is regarded as a form of sexual selection.


Cardiopathy of aging: are the changes related to congestive heart failure?

Over the years, hemodynamic stresses and biologic changes bring about reduced cardiac function. The addition of one or more types of organic heart disease leds to further deterioration of fuction. This is why elderly patients require special consideration and management, why their clinical manifestations and therapeutic responses differ from those in young patients. Although no single abnormality characterizes the aging process, cellular, functional, and structural changes support the existence of a cardiopathy. However, there are insufficient data to link so-called senile cardiopathy directly to otherwise unexplained heart failure. Failure is usually due to the typical reasons, i.e., coronary artery or valvular disease, hypertension, amyloidosis, and chronic pulmonary lesions. Nevertheless, the possibility of senile heart failure should not be overlooked in case of impending or actual myocardial failure. In patients over 60, edema, dyspnea, or tachycardia cannot always be attributed to heart disease. It is hazardous to diagnose and prescribe treatment for cardiac failure if the heart shadow is not enlarged on the x-ray,the circulation time is not prolonged, and the heart sounds and rhythmare normal. Other reasons for the complaints should be looked for, even when the heart rate is fast.


The special problems of heart disease in old people.

The major difference between heart disease in the old and the young is that elderly people almost have one or more other major, even life-threateninng conditions. These associated diseases challenge the physician in establishing a diagnosis and prognosis, understanding the pathogenesis of the symptoms and signs, and determining the best managemnt. Another important difference is that old persons have senescent changes in all organ systems, whether the heart is normal or diseased. Dyspnea, especially on exertion, is common, and so is edema of the feet and ankles. Chest x-rays show changes typical of old age, e.g., small lung fields, mild to moderate pulmonary fibrosis, and calcium plaques in the aorta. In the absence of cardiac disease, the heart is normal in size or even small. Translationg experience in managing heart disease in young patients to elderly patients must be done cautiously. Old people tend to be confused, delicate, mentally and physically slow, feeble, and unreliable, and they are more sensitive to most-if not all-drugs, especially digitalis. The physician should see them often and question them routinely about their symptoms, signs, and medication. Decisions on management should not be hurried, except in an emergency situation.


Using noninvasive methods to study the aging heart.

Except in unusual cases, complex or invasive techniques aren't necessary to examine the heart of an elderly patient. Noninvasive methods currently being used are electrocardiography, arterial and venous pulse tracings, echocardiography, and roentgenology. Interesting data have been collected by correlating phonocardiographic with echocardiographic tracings of the mitral valve, as well as with arterial pulse tracings. Two findings that should prevent a hasty diagnosis of heart disease are that the senile heart often has an abnormal fouth sound and that a systolic murmur can be heard in one of five persons. Other studies have shown that about one-third of patients have some type of heart block and that the interval between the aortic component of the second heart sound and the peak of the early diastolic wave of the mitral echogram is longer in old persons.


The issues in geriatric medical education and postgraduate training: old problems in a new field.

To meet the needs of old patients and young physicians, all medical schools and hospitals should have geriatric courses, residency training programs, and geriatricians to lead these programs.


The establishment of criteria for "quiescence" in ageing human embryo cell cultures and their response to a proliferative stimulus.

Experimental observations have shown that late passage cultured cells have a different growth pattern from early passage cells. For a meaningful comparison of the response of "quiescent" ageing cells to a proliferative stimulus it was, therefore, necessary to use cells in comparable states of "quiescence". Criteria have been established for defining quiescence in ageing cells which include alterations in cell number, ability to transport non-metabolizable substrates and inability to incorporate 3H-thymidine. Using cells of different ages in comparable quiescent states, it has been shown that a smaller proportion of older cells reacted to a proliferative stimulus, and the time taken to respond was longer.


Sex differences in overt personality patterns in older men and women.

A population of 118 older persons, 59--90 years of age, completed an adaptation of the short version of the Bortner rating scale. The seven scales and a total score were analyzed in separate 2 (sex) X 2 (age) analyses of variance to examine sex and age differences in overt personality patterns in men and women under and over the age of 70. Although the results in no way presume to characterize these older persons as prototype A-B personalities, for theoretical reasons, the women reflected significantly stronger pattern A behavior than the men regardless of age. The Bortner scale appears to offer a crude but effective measure of overt "Type Active" behavior -- aggressiveness, expressiveness, and time-conscious activity -- which is consistent with reports of sex differences in intrapsychic and psychosocial adaptive measures of personality. The lack of any main effect due to age is also in line with previous reports that age appears to be a significant variable in internal personality processes rather than external or overt aspects of personality.


Alterations in the numerical density of perichromatin granules in different tissues during ageing and cell differentiation.

Perichromatin granules (PG) were counted on electron micrographs of different tissues taken from young and old female Wistar rats as well as in the basal and spinous layers of adult human epidermis. A significant age-dependent decrease was observed in the following cell types: large brain cortical cells, cerebellar granular cells, hepatocytes, parotid gland cells. No significant decrease was found in the heart muscle nuclei and in the erythroblasts of identical maturation level. The number of PG decreased during the erythroblast maturation almost to zero, and increased in the cells of spinous layer of human epidermis as compared to the basal cells. There is a very wide variation in the number of PG per nucleus between the different tissues. The correlation between the transcriptional activity, the protein synthesis, ageing and cell differentiation is discussed.


Influence of age and different drugs on the healing process in human skin wounds.

The paper contains the results the authors obtained when following, by means of electron-microscopic examination, the healing process of skin specimens after tetracyclin and hydrocortisone administration with regard to age. The results were compared to those in experiments, in which the healing of skin wounds in animals was judged by both mechanical tests and autoradiographic evaluations of the fibroblastic and epithelial reaction. It has been found that in the electron-optical picture age reduces the functional activity of the fibroblasts, delays contraction and permits the phase of exudation pass over to that of proliferation. After tetracyclin and hydrocortisone there were no structural changes in the fibroblasts; on the contrary, tetracyclin supported collagenization and both of them further suppressed exudation, which proved to be very favourable in the process of healing.


Gastric histology and its relation to anaemia in the elderly.

During 1 year 725 consecutive patients admitted to a geriatric unit were investigated for anaemia. 51% of men had haemoglobin levels below 13.5 g/dl and 41% of women had levels below 12 g/dl. 657 patients had an azuresin tubeless test meal following an augmented dose of histamine acid phosphate and 450 (68%) had achlorhydria. Gastric biopsies were performed on 240 of the patients with achloryhdria and 201 satisfactory biopsies were obtained. These were graded into five categories: (1) normal; (2) surface gastritis; (3) diffuse gastritis; (4) chronic atrophic gastritis, and (5) chronic atrophic gastritis with intestinal metaplasia. The grades of mucosal change could not be correlated with the presence or absence of anaemia, the state of gastric function as measured by the Schilling test for absorption of vitamin B12, or the level of vitamin B12 in the serum.


Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5'-phosphate.

Plasma levels of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be significantly lower than normal in 22 out of 31 patients with decompensated cirrhosis or subacute hepatic necrosis. There was no significant difference in plasma PLP levels between those with liver disease due to alcohol and those with other varieties. When intravenous supplements with pyridoxine hydrochloride were given only 33% responded with an increase in plasma PLP. In contrast, all patients given PLP responded, although peak plasma levels were variable, the response being significantly less than that found in normal control subjects. After supplementation with pyridoxine hydrochloride, and with PLP, the urinary excretion of 4-pyridoxic acid, which is derived from the degradation of PLP, was higher in patients who showed the least increase in plasma PLP levels. Although impaired phosphorylation of pyridoxine hydrochloride may be one factor, the most likely explanation for these findings is an increased rate of PLP degradation which may be important in the pathogenesis of vitamin B6 deficiency in patients with severe liver disease.


Detection, by three techniques, of hepatitis B surface antigen (HBsAg) and determination of HBsAg and anti-HBs titres in patients with chronic liver disease.

The sensitivities of three technqiues used to detect serum hepatitis B surface antigen (HBsAg) were compared in 411 patients with various types of chronic liver disease. Counterimmunoelectrophoresis proved an unreliable test. Two haemagglutination technqiues were slightly less sensitive than radioimmunoassay but were more rapidly performed. Less sensitive techniques were particularly unreliable in active liver disease where HBsAg titres were low. HBsAg was detected in patients with chronic persistent hepatitis, alcoholic liver disease, chronic active liver disease with or without cirrhosis, and primary liver cell carcinoma. Forty-six of the 68 (68%) HBsAg positive subjects were males coming from outside the United Kingdom. The HBsAg titres in 13 subjects with chronic persistent hepatitis were significantly higher (P less than 0-001) than those in 43 subjects with chronic active liver disease. Corticosteroid therapy did not alter the HBsAg titre significantly. None of the 28 HBsAg positive subjects studied serially for up to two years cleared HBsAg from the serum. Anti-HBs was examined by passive haemagglutination and found in 35 subjects, 26 of whom had no evidence of liver disease, 80% came from abroad. Anti-HBs was believed to be of epidemiological rather than of pathological importance.


Consequences of partial and subtotal colectomy in the rat.

Rats were subjects to right hemicolectomy (including removal of the caecum), left hemicolectomy or subtotal colectomy. Body weight resumed and maintained a rate of increase very similar to that in control rats. After hemicolectomy, food intake showed no change. Faecal weight increased by about one-third after right hemicolectomy, but did not increase after left hemicolectomy. After right hemicolectomy, the remaining--that is, downstream--portion of the colon showed increase in weight, and so did the (upstream) small intestine, in which the increase involved all three-thirds of its length and was predominantly mucosal. No such changes in the remaining colon or in small intestine were found after left hemicolectomy. After subtotal hemicolectomy, rats ate 30-40% more food than control rats, and faecal weight increased 60% at three months after operation. Study of energy intake and output indicated diminished absorption. All three-thirds of the small intestine showed increase in weight, predominantly mucosal in the upper two-thirds and predominantly seromuscular in the lowest third; villi were taller at all levels. Evidence suggests that the increase in food intake is not due to cessation of coprophagy, and that the small intestine changes are not due solely to increased food intake and occur when the colon is bypassed but not removed.


Lactate dehydrogenase isoenzyme pattern in uninvolved mucosa of patients with colorectal carcinoma.

Colorectal mucosa from patients with colorectal carcinoma was compared with rectal mucosa from a control group. It was found that the LDH isoenzyme pattern of uninvolved mucosa proximal and distal to the carcinoma differed from that of normal tissue and resembled that of carcinoma tissue except in the case of the uninvolved mucosa proximal to the carcinoma of the sigmoid colon, which did not differ from normal mucosa.


Reinvestigation of lactose intolerant children: lack of correlation between continuing lactose intolerance and small intestinal morphology, disaccharidase activity, and lactose tolerance tests.

Thirty children on a lactose-free diet aged from 2-38 months who had previously been diagnosed as having secondary lactose intolerance were reinvestigated on 32 occasions by an oral lactose tolerance test, small intestinal biopsy, and measurement of disaccharidase activity in order to detect the presence of continuing lactose intolerance before reintroduction of milk. No correlation was found between continuing lactose intolerance, as diagnosed by the development of watery stools containing excess reducing substances after an oral load of lactose, and maximum blood glucose rise during a lactose tolerance test, lactase levels, and small intestinal morphology.


Coxsackie and mumpsvirus infection in a prospective study of acute pancreatitis.

A prospective study of 116 patients with acute pancreatitis included routine screening for evidence of viral infection. Five patients (all female) exhibited significant rising antibody titres to Coxsackie B or mumpsvirus, while none of the remaining 111 patients did. Diarrhoea was a prodromal feature of the pancreatitis in those patients with evidence of viral disease. Screening patients with acute pancreatitis for Coxsackie B and mumpsvirus infections is worthwhile in the identification of aetiological factors and may minimise protracted biliary investigations. The incidence of "idiopathic" acute pancreatitis in this study was 5-2% (six patients).


Basal gastric secretion: reproducibility and relationship with duodenal ulceration.

Basal gastric secretion was examined in control subjects, patients with duodenal ulcer, and patients after vagotomy with or without a drainage procedure, not only in terms of conventional indices of secretion--volume, titratable aciditiy, and acid output--but also in terms of the volume corrected for pyloric losses and duodenal reflux (Vg). In all groups, secretion was less in the second than in the first half-hour of a one-hour basal collection. Basal secretion was examined on more than one occasion in non-operated subjects and patients after vagotomy with or without a drainage procedure. In both groups extreme variability in secretion was found from one study to the next, and the variability was the same whether secretion was expressed in terms of conventional indices or VG. It is concluded that such variability is physiological rather than due to experimental errors. Basal secretion was found on average to be greater in duodenal ulcer patients than in control subjects, and, after vagotomy, to be greater in patients with recurrent ulcer than in asymptomatic patients. However, despite all the corrections made, the overlap in the results from the different groups was so great that basal secretion could not be ascribed an aetiological role in the majority of patients with duodenal ulcer.


Significance of Ca-soap formation for calcium absorption in the rat.

The significance of calcium soap formation in the inhibition of calcium absorption has been studied in rats. 47Ca labelled soaps of fatty acids were introduced into the duodenum and the absorption of calcium measured after four hours in a whole body counter. The absorption of calcium was inversely correlated with the chain length of the fatty acid varying from 1% for Ca-stearate to 60% for Ca-hexanoate. Increasing the degree of unsaturation of the fatty acid was accompanied by increased calcium absorption. The availability of calcium for absorption from the soaps was correlated with their solubility in 1% aqueous Na-tauroglycocholate. The percentages of calcium as soap in the small intestine and the faeces after intragastric administration of calcium and fats were similar, which suggests that the faecal content of calcium soaps is an index of intestinal soap formation. Soap formation was negligible when CaCl2 was given with tristearate, triolaeate, or tridecanoate and no depression of calcium absorption was observed. Calcium absorption was markedly impaired by the addition of phosphates at a Ca/P ratio of 1:1 irrespective of the presence of neutral fats. Stearic acid resulted in significant soap formation and reduced calcium absorption. The degree of Ca-soap formation and the inhibition of calcium absorption were well correlated. The results suggest that, although calcium soap formation may markedly depress calcium absorption in the rat, no significant soap formation takes place when fats are given in the form of triglycerides.


Speed of change in biliary lipids and bile acids with chenodeoxycholic acid--is intermittent therapy feasible?

To see whehter intermittent chenodeoxycholic acid (CDCA) therapy is a potential alternative to continous treatment for gallstone dissolution, the speed of change in bile lipid composition was studied after starting and stopping CDCA therapy. In addition, the relationship between bile lipid composition and the proportions of the bile acids was examined. Bile-rich duodenal fluid was collected twice in the first week and then at approximately weekly intervals for four to six weeks, from six gallstone patients starting 13-15 mg CDCA.kg BW-1 day-1 and from another group of six patients whose treatment was stopped after gallstone dissolution. After starting treatment, the mean biliary cholesterol saturation index (based on criteria of Hegardt and Dam, 1971) decreased from 1-49 +/- SEM 0-17 to 0-92 +/- 0-13 at three weeks and 0-88 +/- 0-10 at four weeks, by which time bile lipid composition had become relatively constant. In patients whose treatment was stopped, bile reverted to its supersaturated state within one week, changing from an on-treatment mean saturation index of 0-74 +/- 0-10 to 1-15 +/- 0-15 in six to eight days after withdrawing CDCA. The proportion of conjugated CDCA in the biliary bile acids increased from 27-9 +/- 2-5% to 60-5 +/- 4-2% within four days and to 80-7 +/- 6-2% by four weeks after starting CDCA. When treatment was stopped, the proportion of CDCA reverted to pretreatment levels by two to three weeks. The saturation index was significantly related (P less than 0-001) to the percent of conjugated CDCA present, such that when the proportion of CDCA exceeded 70%, bile was almost invariably unsaturated. Since the mean time taken for bile to become unsaturated was not shorter than the time taken for bile to revert to its supersaturated state, it seems that intermittent treatment would not be adequate to maintain an unsaturated bile and is, therefore, unlikely to be as effective as continuous treatment in dissolving gallstones.


Nitrite and thiocyanate in the fasting and secreting stomach and in saliva.

The concentrations of nitrite and thiocyanate in fasting and pentagastrin stimulated gastric juice and in saliva have been examined. Nitrite was found in all of 17 samples of fasting gastric juice, mean 4-9 +/- 1-1 muM. Stimulation of gastric secretion with pentagastrin caused no significant change in nitrite concentration. Thiocyanate was detected in all of 21 samples of fasting gastric juice and the difference in concentration between smokers and non-smokers probably reflects similar differences in saliva. In contrast to the nitrite data there was a significant drop in thiocyanate concentration of gastric juice after pentagastrin from 0-9 +/- 0-1 mM to 0-3 +/- 0-04 mM, suggesting a salivary origin for the thiocyanate in gastric juice. Thiocyanate is a powerful catalyst of nitrosation, which, together with small amounts of nitrite and naturally occurring amines could lead to the intragastric formation of carcinogenic nitrosamines and in certain circumstances be a factor in the aetiology of gastric cancer.


Production and characteristics of the exocellular polysaccharide in mutant strains of Xanthomonas fuscans.

Production of the exocellular polysaccharide of the phytopathogenic bacterium Xanthomonas fuscans was investigated with respect to its possible use in utilization of industrial wastes containing lactose. Six stable lac+ mutants were obtained after the treatment with N-methyl-N-nitroso-N'-nitroguanidine. The mutants were compared with the parent strain. Morphological and cultivation characteristics, as well as production of the exocellular polysaccharide were compared. The production was found to be maximal during the stationary phase of growth in strains cultivated under submerged conditions. Gas chromatography revealed that the polysaccharide of the parent strain is formed by alpha- and beta-D-glucose and alpha- and beta-D-mannose with a small amount of D-ribose and 6-deoxy-L-mannose. Composition of the polysaccharides produced by the mutant strains (lac+) does not qualitatively differ from that of the parent strain. However, they were found to contain a higher quantity of D-mannose, which is favourable for their industrial utilization.


Relationship between amino acid production and phosphate-dissolving capacity of bacteria.

The ability of soil bacteria to produce amino acids (alanine, aspartic acid, leucine, arginine, glutamic acid, and lysine) was related to the ability to dissolve inorganic phosphate. With the exception of lysine, amino acid production increased with increasing ability to dissolve phosphate.


alpha-Mannosidase and mannanase of some wood-rotting fungi.

Cultivation media from 11 wood-rotting fungi contained alpha-mannosidase and mannanase activity, alpha-Mannosidase was studied in more detail in Phellinus abietis and mannanase was studied more intimately in basidiomycetes Phellinus abietis, Trametes sanguinea and Pholiota aurivella. Suitable cultivation conditions and optimum conditions for the production of alpha-mannosidase and mannanase were determined. Both enzymes are constitutive; mannanase is extracellular, alpha-mannosidase was found in both mycelium and cultivation medium.


Contribution of pantomography to forensic odontology.

Dento-maxillary pantomography is an excellent means of investigating the oral sphere and its maxillary connections. This type of radiographic recording can be particularly useful in forensic odontology when trying to identify a person from certain selected indications [9] or from a greater range of data [7]. In the first case, the original picture provides sufficient support for the evaluation of the reference indications. In the second case, our proposed method should enable the expert to normalize his examinations with the assistance of analytical patterns consistent with a conventional classification. The processing of the pictures submitted to the expert is performed by the use of 3 different analyzers which facilitate the integral transcription of the data. It thus becomes possible for the expert to establish a rigorously exact relation through comparison and assimilation of previously recorded standards. This method should permit specialists to construct information files for all particularly exposed professional groups. It is suited for data processing of the collected formulas and may allow certain statistical evaluations (e.g. pathological, anthropological).


Toxicological investigations of cases of death involving codeine and dihydrocodeine.

Drug levels in post-mortem specimens from 6 cases of poisoning involving codeine or dihydrocodeine have been determined using a direct extraction method followed by gas liquid chromatography. The relevant case histories are described. A preliminary qualitative investigation of dihydrocodeine metabolism has been described involving the analysis of urine samples by thin layer and gas chromatography.


Fatal poisoning by potassium in human and rabbit.

An unusual case of suicidal poisoning by intra venous injection of K+ is presented to demonstrate the limitations of toxicological analysis of post-mortem examination in such a case. Its potential for a "clean undetectable murder" in a homicidal situation is indicated, the parallel being intra muscular insulin/penicillin poisoning which on the other hand are detectable. The intra venous lethal dose is approximately 30-35 mg K+/kg (Human/Rabbits).


[The copper IUD as an alternative to the "pill". Experiences with the intrauterine device Gyne-T].

The author reports upon his experiences with the copper-IUCD Gyne-T in 100 cases. With careful selection of appropriate patients and wary procedure there were no difficulties of insertion, not even in nulliparous women. In the majority of cases the IUCD was inserted because of contraindication or intolerance of hormonal contraceptives. 68 women had no complaints at all, 32 showed unwanted reactions, mostly bleeding disturbances, dysmenorrhoea or inflammation. These, however, occurred only temporarily or could be relieved by therapy. In 4 cases only the IUD had to be removed for medical reasons; in 2 cases it was expelled. Perforations or pregnancies did not occur. Thus the insertion of Gyne-T seems to be an effective, practicable and acceptable contraceptive method, particularly as alternative to hormonal contraception.


[Injuries and emergencies in othorhinolaryngology. Diagnosis and immediate therapy. 1. Injuries of the ear].

Following the general discussion of the causes of accidents and emergencies in the ENT-field, important accident-situations are classified and explained according to anatomical criteria. The differential diagnostic aspects as well as possibilities of first aid are discussed. The most important aspect of first aid is to assess the situation correctly in regard to acute dangers and prospective damage. Important problems and correct guide-lines for first aid at the site of accident are mentioned and discussed.


[Therapy of herpes zoster through active premunization. 2. Treatment of zoster patients, results of experimental and clinical studies, treatment results].

A brief review of the previous and generally inadequate methods for the treatment of  Herpes Zoster is presented. The concept of "active premunization" by appropriate inducer to provide an objective treatment is  defined. A "Premunization Inducer" (PIND) based on a particular non-infectious preparation of an avian pox ("avipox") virus has been shown to enhance non-specific defence mechanisms in the host by T-cell stimulation and to inhibit virus proliferation by the induction of Interferon. The mode of action, efficacy against different viruses and the safety of the preparation is described and discussed. 114 patients with Herpes Zoster were treated with this "premunization Inducer" either orally (for buccal absorption) or by means of a nasal spray. There were no side effects and in all cases there was a marked reduction in the duration of the illness up to the shedding of the last scab (about 15 days instead of the more usual 31 days). Pain was relieved in some cases within 6 hours and in the remainder within 2 days: a rapid resolution of the inflammation could be observed. There were practically no signs of postherpetic neurological complications among the patients treated (the usual incidence of post-herpetic neuritis is around 18%). The treatment of Herpes I and Herpes II infection other viral conditions will be reported elsewhere.


Possibilities of determining the person steering a surface-craft or an aircraft at the time of accident (impact).

Accident investigators are often confronted with the fact that there are doubts with regard to the person who has piloted a vehicle at the time of the accident. By securing all traces in or on the vehicle and on the clothes of the persons on board it will be possible to identify the person who has been piloting the vehicle. Evidence can also be obtained from blood-traces, the remnants of human tissue and hair and textile fibres and by the abrasion of synthetics and of paint as well as by characteristic deformations. The controls (steering-wheel or horn, pedals, etc.) and their traces on the gloves and shoes of the pilot must be taken into account, and vice versa.