A general method of decomposing a difference between two rates into several components. In her work on the components of a difference between two rates, Kitagawa (1955) was successful in dividing the difference into the rate effect and the effect of the factor, for data classified by one factor. Her formulation for data classified by two factors, however, involves an interaction term which is difficult to interpret. Retherford and Cho (1973) devised a method that does not include any interaction terms. However, their method has other limitations, such as the dependence of the results on the order in which the effects of the factors are computed. In this paper, we provide a general method capable of handling any number of factors, which is developed along the lines suggested by Kitagawa and by Retherford and Cho but without the limitations of their methods.


Temazepam (Euhypnos) and chlormethiazole: a comparative study in geriatric patients. The sleep-inducing properties and tolerance of temazepam formulated in solution in soft gelatine capsules were compared with chlormethiazole syrup in two groups of geriatric in-patients. Both compounds appeared to be safe, effective and well-tolerated, but significant differences in favour of temazepam were observed in quality and duration of sleep, ease of awakening and carry-over effects. This formulation of temazepam (Euhypnos) would appear to be an ideal sleep-inducer for geriatric patients.


Influence of sulphinpyranzone (Anturan) on thrombo-elastography. Sulphinpyrazone (Anturan, 200 mg four times daily) was administered orally to 10 patients for two weeks. Thrombo-elastographic determinations revealed no disturbance of coagulation and it may therefore be concluded that Anturan can also be safely administered pre-operatively.


A multicentre evaluation of sustained release oxprenolol in the management of hypertension in hospital out-patient practice. One hundred and two patients with essential hypertension, managed in hospital out-patient clinics in the United Kingdom on a drug regime of beta-receptor antagonist alone, or in combination with a diuretic were successfully transferred to once daily sustained release oxprenolol. Where a diuretic was prescribed the dose remained unchanged. Improved control of blood pressure was recorded in the majority of patients with one or two morning tablets of sustained release oxprenolol. Preference for once daily therapy, enthusiasm for the calendar pack, and a net increase in the mean daily dosage of a beta-receptor antagonist were the probable factors contributing to the improvement recorded. Once daily sustained release oxprenolol would appear, in most hypertensive patients, to be an effective substitute for multi-dose treatment with beta-receptor antagonists in conventional formulation.


Tanderil/chloramphenicol eye ointment in the treatment of the "Red Eye" seen in general practice. An open study is reported in which 35 general practitioners treated 128 patients suffering from 'Red Eye' with a new eye ointment containing 10% Tanderil(oxyphenbutazone) and 1% chloramphenicol. One hundred and seventeen patients completed the seven day treatment period, in which time 99 had completed resolution of the symptoms and were discharged, the remaining 18 patients needed a longer period of treatment. Eleven patients failed to complete the study period, of whom 5 patients were subsequently referred to a specialist and 6 had their treatment changed by the general practitioner. Six patients showed signs of allergy to the ointment, all of whom were being treated for allergic conjunctivitis. Seventeen per cent of patients had some difficulty in applying the eye ointment or complained of subsequent blurring of vision.


A comparison of the efficacy and safety of extra-amniotic prostaglandin E2 and intravenous prostaglandin E2 for the induction of labour in patients with unripe cervices. In a study comparing intravenous prostaglandin E2 (PGE2) with extra-amniotic PGE2 for the induction of labour, in patients with unfavourable induction features, we found no difference between the two methods in either safety or efficacy. However, we would not recommend the use of the extra-amninotic route as a routine method because of some technical difficulties.


Species-specific auditory discrimination in bobtail quail neonates. Incubator-hatched bobwhite quail neonates were tested individually in a variety of single call and simultaneous auditory choice tests involving 6 adult quail vocalizations and a chicken exodus call. The quail showed a high degree of responsiveness (100%) to 3 adult quail vocalizations and significantly less responsiveness (40-50%) to 3 other quail calls and to the chicken exodus call in single call tests. In simultaneous choice tests, the quail were selectively responsive to a call of their own species over the chicken call, and they also showed certain intraspecific preferences. Because of their high degree of responsiveness, coupled with selectivity of their approach responses, bobwhite quail neonates are ideal for the laboratory investigation of the development of auditory perception.


The effect of visual deprivation in the rat on transfer effects after form discrimination training. In 3 experiments the performances of light-reared (LR) and dark-reared (DR) 90-day-old rats were compared on a variety of transfer tests following acquisition of 3 discriminations involving patterns of small squares (dots). Though no significant difference due to rearing condition was found in acquisition of those discriminations consisting of single lines of dots in various orientations, transfer tests did reveal subtle differences in the way LR and DR rats analyze contour information. Significant differences due to rearing were also observed on the acquisition of a complex dot pattern (gradient vs X) and, in spite of overtraining, on subsequent stimulus equivalence tests. Anomalous transfer effects were not observed in any of these test situations.


Postweaning environmental stimulation and somesthetic performance in rats sustaining cortical lesions at maturity. Rats were enucleated at 28 days of age and were assigned to complex or relatively barren tactile environments for the duration of the experiment. Approximately half of the animals in each group received large, bilateral lesions of the somatosensory cortex when they were 60 days of age, and the remainder underwent sham operations. Twenty days later all groups were tested for the ability to master a series of tactile discriminations. Statistical tests revealed a highly significant lesion effect, but no environment or lesion x environment interaction effects. These sensory discriminative findings stand in contrast to some earlier reports which have shown that environmental complexity provided prior to or following other forebrain lesions can minimize error scores on simple learning tasks.


The development of sexual behavior in the rat: role of preadult nutrition and environmental conditions. Rats were subjected to pre- and postnatal undernutrition by restricting the food intake of their mothers (U); another group of rats was normally fed (N). Each nutrition group was divided into 3 subgroups by varying the degree of environmental stimulation: animals in the Max group were stimulated by handling and enriched rearing conditions; the Min group rats were subjected to social isolation; rats in the control condition (C) were raised under ordinary laboratory conditions. The onset of sexual activity was not affected in the U-C male rats, but was delayed in both U-Min and N-Min rats. Although no difference existed in the age of puberty between the N-Max and N-C animals, the U-Max rats displayed an advancement of puberty by 7 days in comparison to the U-C rats.  Undernutrition did not affect female sexual maturation; however the Max condition delayed this process in both nutrition groups.


Exploration, distraction, and habituation in rats reared in isolation. Rats reared in isolation have been reported to show increased motor activity; the purpose of the present experiment was to establish whether they also show enhanced exploratory and orienting responses. Rats were reared in isolation or in social groups from Day 20 to Day 45. Subgroups of each rearing condition were either left undisturbed, received daily handling, or received daily handling and were given objects in their cages. From Day 45 all the rats were rehoused in groups of 6, and testing began at Day 73. In a 1st test exploration was measured by the number of contacts with objects placed in the home cage; and a 2nd test exploration was measured by responses to a holeboard; and in a 3rd test orienting was measured by the distraction produced by the presentation of a tone. When tested in novel situations, in contrast to their enhanced motor activity, isolates showed reduced exploration and orienting. This may have been due to a discrepancy between their adaptation level (established during rearing) and their current level of sensory input. In all the tests the isolates showed normal habituation, both within sessions and between sessions. An inability to habituate is not, as has been claimed, a general characteristic of isolates.


Syntheses of C-peptides and human proinsulin. Syntheses of human, dog, rat, and duck C-peptides and their analogues and preliminary results on the total synthesis of human proinsulin are described. In the syntheses of the C-peptides, chain elongation was performed exclusively by the azide-fragment condensation method in solution. The synthetic human, dog, rat, and duck C-peptides and their analogues were proved to be homogeneous by several analytic means. With these synthetic peptides, radioimmunoassay systems for dog, rat, and duck C-peptides were developed. For the total synthesis of human proinsulin, 10 protected peptide hydrazides were prepared, and the linearly protected hexaoctacontapeptide having the proposed sequence of human proinsulin was constructed by the azide-fragment condensation method in solution starting from the C-terminal undecapeptide (HP 75-86). After deblocking of the alpha-amino protection, the partially protected hexaoctacontapeptide was treated with sodium in liquid ammonia. The ensuing sulfhydryl form was converted to the S-sulfonate form, which was reduced and then air-oxidized. The oxidized material was purified by gel filtration on Sephadex G-50 (fine) followed by ion-exchange chromatography on DEAE-cellulose. The cross-reactivity in the insulin radioimmunoassay of the ensuing product was 62.5 per cent of porcine proinsulin on a weight basis at B/Bo = 60 per cent. Acid hydrolysis and amino acid analysis of this product gave the theoretically expected ratios. In addition, this peptide, as well as the S-sulfonate form of the hexaoctacontapeptide, showed displacement curves superimposable on that of synthetic human C-peptide on an equimolar basis in the human C-peptide radioimmunoassay (antiserum 527). These results confirm the synthesis of human proinsulin.


On the preparation and characterization of standard materials for natural human proinsulin and C-peptide. The preparation and characterization of intact native human proinsulin and C-peptide to serve as reference standards in immunologic and biologic assays is described. The major difficulty encountered in the preparation of human proinsulin from crystalline human insulin is the rather low yield (0.08 per cent), which may be due to postmortem autolysis in the pancreatic specimens. Under such circumstances, minor degrees of contamination of batches by fresh pancreases from other species, such as cows or pigs, may be magnified considerably. Such contamination can be readily detected with various currently available proinsulin- or C-peptide-specific antisera. Autolysis before or during preparation may also affect the yields and quality of human C-peptide preparations. Some of these C-peptide by-products are described, along with methods for their purification and characterization.


Kinetics of human C-peptide in man.

Kinetics of human C-peptide in man. A review of studies concerned with the metabolism of human C-peptide showed that the kidney is the major organ in C-peptide removal. The turnover rate of C-peptide was similar to that of proinsulin but considerably slower than that of insulin. An analysis of corresponding C-peptide and insulin concentrations in normal subjects after the administration of oral glucose or intravenous glucagon was used to define the relationships between the two peptides. These results show that different peripheral vein concentrations of insulin may correspond to identical C-peptide concentrations, depending on sampling conditions.


C-peptide in conditions other than diabetes mellitus. Measurement of serum and urinary C-peptide has been shown to be of value in several conditions other than diabetes mellitus. It is particularly useful because it can distinguish endogenous beta cell secretion from exogenously administered insulin and because circulating insulin-binding antibodies do not interfere with its measurement. Because the liver removes little, if any, C-peptide, peripheral blood values may more accurately reflect beta cell secretion than do peripheral insulin levels. Clinically, serum C-peptide has been most useful in diagnosing hypoglycemic disorders. Diagnosis of insulinomas is facilitated in both diabetic and nondiabetic patients, and surreptitious insulin injection is readily detected. In studies of insulin regulation, circulating C-peptide has been used to demonstrate suppression of endogenous insulin secretion by exogenous insulin. Peripheral insulin and C-peptide levels have been compared in studies of the role of the liver in states of altered insulin homeostasis. Because of its higher urinary clearance, determination of urinary C-peptide is preferable to urinary insulin measurement in situations where frequent blood sampling is impossible or difficult to accomplish.


Early arterial lesions in maturity onset diabetes mellitus detected by an ultrasonic technique. Using an ultrasonic technique preclinical atheroma was studied in maturity onset diabetics. The elasticity of the leg arteries was measured as the elastic modulus in 32 patients and a normal range was established in 13 controls. The elastic modulus was higher (i.e. the arteries were stiffer) in diabetics than controls and this was associated with a higher mean blood pressure in the diabetics. Nine phenformin and 10 chlorpropamide treated diabetics had evidence of more severe arterial disease than 13 diet treated patients. This could not be accounted for by other factors known to influence arterial disease.


Age dependent effects of oxytetracycline in ob/ob mice. The effects of daily oxytetracycline injections on the metabolism and growth of prepubertal, 10 and 24-week old ob/ob and lean mice were examined. Drug treatment (100 mg/kg) between 17 and 28 days of age similarly reduced body weight gain and skeletal growth of both ob/ob and lean mice, but had little effect on obesity, serum glucose, or IRI levels. In older obese mice, 6 days of oxytetracycline led to substantial reductions of serum glucose, serum IRI, and obesity when compared with either ad libitum fed obese mice or food-restricted ob/ob mice serving as weight loss controls. In lean mice oxytetracycline also significantly reduced body weight and serum glucose, while no effects on obesity or IRI levels were noted. The present data show that oxytetracycline reduces the severity of many of the diabetic symptoms of ob/ob mice, but that only the ameliorative effects on obesity and hyperinsulinaemia appear to be specific to the ob/ob genotype.


The effect of insulin on pyruvate dehydrogenase interconversion in heart muscle of alloxan-diabetic rats. Evidence is presented for regulation by insulin of pyruvate dehydrogenase (pdh) interconversion in rat heart muscle in vivo and in vitro. In the alloxan diabetic rat the active (dephospho) enzyme amounted only to 12% of total PDH and was restored to 42% by insulin. Antilipolytic treatment of the dibetic animals was ineffective, indicating that the action of insulin was independent of a lowering of plasma non-esterified fatty acid concentration. On perfusion of isolated hearts from diabetic rats in the presence of glucose the proportion of pyruvate dehydrogenase in the active form remained low but was fully restored upon addition of insulin (2mU/ml) to the medium. No effect of insulin was obtained in the absence of glucose. The correlation  between the rate of pyruvate decarboxylation in the perfused heart and of pyruvate dehydrogenase activity, in vitro, suggests that in the diabetic heart the entry of pyruvate into the citric acid cycle is largely controlled by covalent modification of the pyruvate dehydrogenase complex rather than by feedback inhibition. The possible role of insulin therein is discussed.


Blood lactate and pyruvate levels in diabetic patients treated with biguanides with and without sulphonylureas. Blood lactate and pyruvate were measured two to three hours after breakfast in 153 patients with maturity-onset (type 2) diabetes. Blood lactate was raised in 56% of all patients taking phenformin and in 35% of all patients taking metformin, while 75% and 35% respectively had raised pyruvate. Mean blood lactate level was raised at 2.2 mmol/1 (range 0.2-4.4 mmol/1) in the patients on phenformin and 1.7 mmol/1 (range 0.2-4.3 mmol/1) in those on metformin, with mean blood pyruvate levels of 0.122 mmol/1 (range 0.050-0.215 mmol/1) and 0.111 mmol/1 (range 0.038-0.259 mmol/1) respectively. In patients treated with a sulphonylurea drug alone mean blood lactate and pyruvate levels were not increased and were no different in those receiving sulphonylurea therapy in addition to a biguanide from those receiving a biguanide alone. Blood lactate did not correlate with any clinical or biochemical measurement in any of the treatment groups except for a correlation with serum creatinine in those patients taking metformin alone. The finding of raised blood lactate levels in diabetic patients treated with metformin suggests that this drug should be prescribed with caution.


Change of insulin dosage, circulating free and bound insulin and insulin antibodies on transferring diabetics from conventional to highly purified porcine insulin. Fifty-eight patients on long term conventional mainly bovine insulins have been transferred to highly purified porcine insulin preparations. There was an overall reduction of 22% in daily insulin dosage and improved diabetic control as shown by decreased blood glucose concentration. Increased concentrations of serum free insulin and falls in serum bound insulin levels were also found. There were reductions in the serum binding capacities and affinity constants on changeover from conventional to highly purified insulin due to a combination of the effects of differential conventional/purified porcine binding and the substitution of a low antigenicity insulin. However, 12 of the patients receiving higher doses of insulin experienced marked hypoglycaemic reactions immediately on insulin changeover despite initial dosage reductions of 30% and prior to any changes in antibody characteristics.


[Long-term cardiac pacing: survival above 10 years (author's transl)]. The authors reports data of pacemaker patients surviving above 10 years. They have considered 241 patients undergone pace-maker first insertion from January 1961 to June 1967 (168 treated with epicardial and 73 with transvenous electrodes). At the last control on July 1977, 52 (27 males and 25 females) were surviving, equivalent to 21% of all patients treated in that period. The age of these patients ranged from 5 to 83 (mean 60 years) at first implantation. At present 51 patients are treated with transvenous systems, only 1 patient is stimulated with epicardial pace-maker. 382 pace-makers were used in these 52 patients: the average life of every pacer was 20 months. Complications relative to epicardial and endocardial pacing are reported: with the transvenous system the percent of complications was lower (15,6% to 50,4%). Finally present clinical states of the 52 patients are reported, basing on the reccomendations of Criteria Committee of the New Heart Association.


[Apparently unusual causes of inhibition of demand unipolar pacemakers (author's transl)]. An unusual behaviour observed in five demand endoventricular unipolar pacemakers is reported: the pacing were inhibited by coughing, deep inspirations and Valsalva manoeuvre. The findings allowed to point following remarks: a) the inhibition is related to myopotentials caused by respiratory movements which involve a large number of thoracic skeletal muscles; b) the myopotential characteristics may be differents in different patients; c) even electronic sensing characteristics may be slightly different in the same kinds and models of the same manufacturer.


[Electrophysiological demonstration of more structures in the atrioventricular node (author's transl)]. Three types of atrioventricular nodal conduction curves, relating A1A2 to H1H2, generated with atrial extrastimulus technique, are known. The first type is smooth, suggesting the homogeneous structure of A-V node. The second type, with abrupt increase in H1H2 response over a critical range of A1A2 coupling intervals, suggests the presence of fast and slow A-V nodal pathways. We have found in five patients the third tipe of A-V conduction curve, giving evidence of an intranodal final common pathway, distal to the fast and slow A-V nodal pathways. The thyrd type of curve enables us to know also some alectrophysiological properties of final common pathway. Indeed we have defined effective and functional refractory periods of fast, slow and final common pathways as far as we can in this type of curve. Paced heart rate variations and atropine medications have led the third type of A-V conduction curve to change into the second type in three cases, into first type in one case. These changes of A-V nodal conduction curves are related to different influence of cardiac cycle lenghts and autonomic nervous system on refractory periods and conduction velocity of the outlined intranodal structures.


[Idiopathic congestive cardiomyopathy. Absence of histopatological for adrenergic hyperactivity (author's transl)]. Extensive histopathological investigation of hearts from patients with idiopathic congestive cardiomyopathy failed to reveal "myofibrillar degeneration", a lesion ascribed specifically to cathecolamine cardiac overstimulation. Morphological support of the theory of adrenergic hyperactivity in the development and progression of this disease is not provided by the present study.


[Sick sinus syndrome treated by ventricular inhibited pacemaker and radiofrequency programmed ventricular stimulation (author's transl)]. It is described a patient with sick sinus syndrome (atrial bradycardia and reciprocating junctional tachycardia) treated by a permanent ventricular inhibited pacemaker. The catheter is been also connected with a radiofrequency device implanted in order to interrupt the reciprocating tachyarrhythmia with programmed ventricular stimulation.


Macrophage turnover in Crohn's disease and ulcerative colitis. Monocytopoietic proliferation activity was determined in 8 patients during severe attacks of Crohn's disease and in 6 patients with ulcerative colitis. Similar results were obtained in both groups of patients. A moderate but significant hyperproliferation of monocytopoiesis was found to be present in about half of the patients, and with some of the remainder of cases, part of the criteria for hyperproliferation were also fulfilled. This indicates that Crohn's disease as well as ulcerative colitis are frequently associated with moderate overproduction of monocytes which may be assumed to be induced by macrophage demand of the affected tissues. In comparison with other diseases involving inflammations, the monocytopoietic hyperproliferation was moderate. Therefore, the inflammation in Crohn's disease and ulcerative colitis seems to be characterized by a relatively low macrophage turnover induced by pathogenetic mechanisms of moderate macrophage toxicity.


Macromolecular secretion by isolated gastric mucosa: fundamental differences in pepsinogen and intrinsic factor secretion. The secretion of pepsinogen and intrinsic factor (IF) in response to various known stimulators and inhibitors of gastric acid secretion was examined in isolated rabbit gastric mucosa maintained in organ culture. Acetylcholine (10(-8) M) stimulated stimulated both pepsinogen (P less than 0.01) and IF (P less than 0.01) secretion and this stimulation was blocked by atropine. Parasympatholytic agents did not alter unstimulated (basal) secretion of pepsinogen even at high concentrations (atropine, 10(-2) M or propanthelene bromide, 5 X 10(-3) M), however, at these concentrations basal IF secretion was abolished. Histamine (10(-4) and 10(-2) M) had no effect on pepsinogen secretion but stimulated IF secretion (P less than 0.001). Antagonism of H2 receptors by cimetidine reduced both basal and histamine-stimulated IF secretion, but pepsinogen secretion remained unaltered. Under the conditions of the above experiments the gastric mucosal surface was not exposed to HCl but was constantly buffered by culture medium at pH 7.4. When we applied 50 mN HCl to the mucosal surface of the biopsies, pepsinogen secretion doubled (P less than 0.001) but IF secretion was abolished. These studies have clearly documented that: (1) fundamental differences exist in the responses of pepsin and IF secreting cells; (2) H+ ions bathing the mucosal surface of the stomach may influence the results of experiments designed to examine the mechanisms of gastric mucosal macromolecular secretion.


Histamine augments gastric ulceration produced by intravenous aspirin in cats. In unanesthetized cats, continuous intravenous infusion of aspirin for 36 hr did not produce gastric ulcers when given alone but did when combined with 160 microgram kg-1 hr-1 of histamine-2HCl intravenously. The ulcers were mainly antral in location. The incidence and severity of ulcers increased with duration of the infusion up to 36 hr and with dose of aspirin up to 4 mg kg-1 hr-1. With the highest doses and longest durations some of the antral ulcers perforated. Antral ulcers occurred in more than half of the cats getting 0.25 mg kg-1 hr-1 or more of aspirin for 36 hr or getting 4 mg kg-1 hr-1 of aspirin for 6 or more hr. Intravenous aspirin plus intragastric infusion of 40 ml hr-1 of 150 mM HCl for 16 hr also produced gastric ulcers. Plasma salicylate concentrations were less than 350 microgram ml-1 with all doses and durations of aspirin used (400 microgram ml-1 is regarded as the upper limit of the therapeutic range in man). These studies show that when the stomach is acidified by giving histamine intravenously or HCl intragastrically, intravenous aspirin produces large deep gastric ulcers. The mechanism of the ulcerogenic action of intravenous aspirin is not known.


Hepatic inactivation of gastrins of various chain lengths in dogs. In dogs with gastric fistulae and with transposition of the portal vein and the inferior vena cava, we studied secretion of acid in response to portal or systemic venous infusion of a series of progressively longer fragments of the carboxyl terminal portion of human gastrin. Pentagastrin, G6, G7, G8, G9, G10, G13, G17, and G34 were studied. Potency by portal venous infusion relative to systemic venous infusion was used as an index of hepatic inactivation. Fragments with eight or fewer amino acid residues were more than 90% inactivated by hepatic transit. Fragments with nine or more amino acid residues were more resistant to hepatic inactivation than shorter fragments. For fragments with 7 to 17 amino acid residues, increasing the chain length was accompanied by progressive increase both in hepatic resistance to inactivation and in potency for stimulation of acid secretion, suggesting that resistance to hepatic inactivation may be a major determinant of potency.


Factors affecting delivery of bile to the duodenum in man. Studies utilizing balloon-occludable T or duodenal tubes in subjects with and without gallbladders were undertaken to identify the contribution of the gallbladder, the sphincter of Oddi, and bile salts to the delivery of bile to the duodenum. Patients with and without a functional sphincter of Oddi and with and without a gallbladder were compared. The presence of a functional sphincter of Oddi in duodenal tube patients reduced bile salt output by more than 67% from that observed in T-tube patients. When cholecystectomized and normal patients were compared using the duodenal tube, peak bile salt output was significantly increased in normal subjects, reflecting gallbladder contraction, but total bile salt output was not significantly increased suggesting that the gallbladder has a minor role in bile delivery. Exogenous infusion of cholecystokinin produced much more stable bile secretion than did endogenous release of cholecystokinin by intraduodenal infusion of essential amino acids. This rhythmic release of bile after endogenous cholecystokinin release was related to the concentration of bile salts in the intestinal lumen. Thus, delivery of bile to the duodenum is wave-like and is predominantly controlled by the sphincter of Oddi.


Pool size, synthesis, and turnover of sulfated and nonsulfated cholic acid and chenodeoxycholic acid in patients with cirrhosis of the liver. In 5 patients with cirrhosis of the liver sulfated and nonsulfated [14C]cholic acid and [14C]chenodeoxycholic acid were administered intravenously and the specific activity curves were determined. Specific activities declined exponentially and pool sizes, synthesis rates, and turnover rates of bile acids were calculated on the basis of a one-pool system. The biological half-life of cholic acid was 4.3 +/- 1.6 days (mean +/- SEM) and of chenodeoxycholic acid was 2.8 +/- 1.2 days. The half-life of cholic acid sulfate was 0.7 +/- 0.5 day and of chenodeoxycholic acid sulfate was 0.8 +/- 0.5 day. The pool size of cholic acid was 513 +/- 103 mg, of chenodeoxycholic acid, 477 +/- 77 mg, of cholic acid sulfate, 4.7 +/- 1.0 mg, and of chenodeoxycholic acid sulfate, 38.7 +/- 4.0 mg. The daily synthesis of cholic acid was 90 +/- 14 mg, of chenodeoxycholic acid, 118 +/- 6 mg, of cholic acid sulfate, 7.2 +/- 2.1 mg, and of chenodeoxycholic acid sulfate was 32.6 +/- 3.2 mg. The data indicate that sulfate esters of bile acids are significantly more rapidly excreted than are unsulfated bile acids. More than one-fourth of the chenodeoxycholic acid but less than one-tenth of the cholic acid formed was sulfated. The preferential sulfation of chenodeoxycholic acid is responsible for the more rapid turnover of chenodeoxycholic acid in comparison to cholic acid. Sulfation enhances the excretion and thereby prevents the accumulation of hepatotoxic concentrations of chenodeoxycholic acid in patients with cirrhosis of the liver.


Left-sided heart failure presenting as hepatitis. Overt liver disease caused by left-sided heart failure is seldom recognized unless there is obvious hypotension. We now report 4 patients whose initial diagnosis was hepatitis but who were later shown to have central hepatic necrosis associated with left ventricular failure. Signs of right-sided heart failure were absent. Hepatitis was initially suspected in 3 patients because of striking transaminase elevations and in 1 patient because of jaundice and symptoms compatible with hepatitis. Liver biopsies performed on all patients revealed central hepatic necrosis without evidence of acute or chronic hepatitis. Left ventricular failure was documented in all 4 patients. One patient had coronary artery disease, and the other three patients had valvular heart disease. Liver function tests became normal or improved in all cases as the underlying heart disease was treated. We believe that liver dysfunction secondary to left ventricular failure is not uncommon and can be seen in the absence of right-sided heart failure or hypotension.


Hepatic failure and death from erythropoietic protoporphyria. A 60-year-old white male presenting with a clinical picture of obstructive jaundice was subsequently found to have erythropoietic protoporphyria. The diagnosis was suspected because of a history of life-long photosensitivity and was confirmed by finding high levels of erythrocyte protoporphyrin. Liver biopsy revealed birefringent deposits of protoporphyrin by polarization microscopy accompanied by severe hepatic injury and fibrosis. The patient died rapidly from liver failure, and at autopsy the biliary tree was patent. Despite the autosomal dominant transmission of erythropoietic protoporphyria, we failed to detect any family members with the disease. This report is concluded with a brief discussion of the liver involvement in erythropoietic protoporphyria.


Longitudinal esophageal bands associated with esophageal aperistalsis: speculations on pathogenesis. A 6-year-old girl with ataxia telangiectasia syndrome was found to have multiple bands longitudinally traversing her esophagus, and esophageal aperistalsis. In the past, the patient was also known to have had esophageal candidiasis. The bands may have been congenital or may have been produced when linear ulcers caused by fungal esophagitis undermined mucosal strips and then healed, leaving tissue bands attached only at their extremities to the esophageal wall. The esophageal motor dysfunction may have been attributable to esophageal candidiasis, or may have been a hitherto unrecognized component of the ataxia telangiectasia syndrome.


Portal hypertension in systemic mastocytosis. We report the case of a 66-year-old male patient with portal hypertension related to systemic mastocytosis. The liver was enlarged; microscopic examination showed portal mast cell infiltration and fibrosis. Portal hypertension was evidenced by splenomegaly, esophageal varices, and increased wedged-free hepatic venous pressure gradient. Arteriography showed that portal vein was patent. Portal hypertension could be the consequence of intrahepatic block due to mast cell infiltration and/or fibrosis of the liver.


Liver support systems: the low clearance of model hepatic excretory anions by charcoal hemoperfusion. The removal of cholephilic anions (unconjugated bilirubin, bromosulfophthalein, and indocyanine green) by charcoal hemoperfusion was assessed in normal dogs. None of these model excretory compounds was effectively removed by the charcoal columns. In vitro studies suggested that poor removal of the anions was related to albumin binding in that, when the anions were in molecular solution, their extraction by the charcoal column was high; however, when albumin was added, their extraction was negligible. Therefore, if the removal from plasma of strongly bound toxins is important in the treatment of acute hepatitic failure, additional support devices may have to be encompassed into the ultimately hepatic support system.


A model of fulminant hepatic failure in the rabbit. A highly reproducible model of fulminant hepatic failure was developed by administering intravenously the selective hepatotoxin galactosamine hydrochloride (4.25 mmoles per kg) to genetically uniform rabbits. The great majority of rabbits died between 21 and 44 hr after injection following a period of coma which lasted 2.6 hr on average. Serum biochemical tests and liver histology reflected massive hepatic injury. Changes in plasma ammonia and amino acid concentrations, in coagulation parameters,  and in the electroencephalogram were similar to those found in human fulminant hepatic failure. This model appears promising for future studies of the pathogenesis and treatment of fulminant hepatic failure.


Alcohol, amino acids, and albumin synthesis. III. Effects of ethanol, acetaldehyde, and 4-methylpyrazole. The effects of ethanol, 4-methylpyrazole (4-MP), and acetaldehyde on albumin and urea synthesis, and on polysome aggregation were studied in isolated perfused rabbit livers. Fed or fasted males served as donors and the perfusate contained ethanol, 200 mg per 100 ml, with and without 1.5 mM 4-MP; or acetaldehyde, 2 mg per 100 ml, with and without 1.5 mM 4-MP. The results indicate that in livers from fed donors ethanol depressed albumin and urea synthesis and bound polysomes were disaggregated. Perfusion with acetaldehyde caused a similar decrease in albumin and urea synthesis, but did not cause polysome disaggregation. The addition of 4-MP to the ethanol perfusates did not enhance albumin or urea synthesis but did prevent polysome disaggregation. When the donor was fasted, the addition of 4-MP to the ethanol perfusates restored urea synthesis and polysome aggregation to fasted control levels. In the livers from fasted donors, acetaldehyde did not lower albumin or urea synthesis and had no effect on polysome aggregation. The results indicate that the hepatic responses to ethanol and acetaldehyde are different if the livers are derived from fed or fasted donors, and it is not possible to ascribe the toxic effects of acetaldehyde or ethanol on albumin and urea synthesis to either agent, per se.


Evidence for the existence of a countercurrent exchanger in the small intestine in man. The vasculature in the human villus forms vascular loops by the supplying arterial vessel and the draining capillaries and/or veins. This study reports two experimental observations that strongly suggest that these vascular loops function as countercurrent exchangers. (1) The elimination of intraarterially injected 85Kr from the human small bowel exhibits an initial very rapid component of the type earlier reported in the feline gut. This component in all probability reflects the extravascular "shunting" in the exchanger of the injected radioactive tracer. (2) When exposing the intestinal mucosa to an isotonic electrolyte solution containing glucose, an osmolality gradient from the tip to the base of the human villi was demonstrated, the tips having an osmolality of around 700 milliosmoles per kg H2O. This hyperosmolality is created by the exchanger acting as a countercurrent multiplier.


Inhibitory role of the distal small intestine on the gastric secretory response to meals in man. The role of the distal small intestine on postprandial gastric function was determined in 6 healthy volunteers by diverting chyme from the intestine at a site 100 cm distal to the ligament of Treitz and comparing the results with those observed in the same subjects when chyme was exposed to the entire gut. Diversion of chyme increased the gastric secretory response, which suggests that the distal small intestine has an inhibitory role in postprandial gastric secretion.


Vasoactive intestinal peptide: quantification by radioimmunoassay in isolated cells, mucosa, and muscle of the hamster intestine. Vasoactive intestinal peptide (VIP) levels were quantified by radioimmunoassay in three strata of hamster bowel wall, namely, epithelial cells isolated by a vibration technique, scrapings of the vibrated intestine, and in the remaining muscle. Expressed on a wet weight basis, highest levels of the peptide (as a percentage of total bowel wall content) were found in the muscle (72%) followed by high levels in scrapings of denuded villi (27%). Villus and crypt epithelial cells, isolated as one fraction, contained very low levels (less than 1%) of total VIP. To correct for differences in water content of the various strata, data were also calculated on the basis of tissue protein. When expressed in this manner, scrapings of denuded villi and the remaining muscle, both areas of dense autonomic innervation, were virtually equal in their VIP content (mean +/- SE, 9.5 +/- 4 and 11 +/- 2 ng per mg of protein, respectively). However, the VIP concentration of the cells was over two orders of magnitude less than the muscle or scrapings of denuded villi (0.02 +/- 0.007 ng per mg of protein). These results suggest that VIP is concentrated with or near the neural elements of the gut.


Factors affecting the absorption and excretion of lead in the rat. A reliable method for studying lead absorption and excretion in rats is described. Lead absorption occurs primarily in theduodenum where lead enters the epithelial mucosal cells. There is a relative mucosal block for lead with increasing intraluminal doses. Certain substances which bind lead and increase its solubility enhance its absorption. Iron, zinc, and calcium decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. The total body burden of lead does not affect lead absorption. Thus, lead does not have a feedback mechanism which limits absorption. Lead absorption is increased during rapid periods of growth and in iron-deficient animals. It is diminished with starvation and in iron-overloaded animals. The excretion and kinetics of tracer doses of radiolead were quantified. Erythrocytes seem to serve an important role in transport. Excretion occurs in urine and stool. Bile is an important route of excretion in the gut. Although most of a tracer dose is rapidly excreted, the excretory process is limited permitting lead accumulation primarily in bone.


Herpes simplex esophagitis after trigeminal nerve surgery. While being followed for reactivation of latent herpes virus infection after surgery for tic douloureux, a patient developed herpetic esophagitis. The patient was not an immunocompromised host in the usual sense of the term. Two possible interrelated, predisposing conditions were identified: (1) oropharyngeal shedding of herpes simplex virus, which frequently follows surgery on the trigeminal nerve, in association with (2) esophageal intubation and presumed mucosal trauma. Symptoms began within 24 hr after virus excretion in the mouth was documented. Esophageal lesions were present and herpes simplex virus was recovered from the biopsy 6 days after symptoms developed. Herpetic esophagitis should be considered when patients developed odynophagia after esophageal instrumentation in association with possible reactivation of latent herpes infection.


Hepatic hemangiomas: pitfalls in scintigraphic detection. The evaluation of solitary hepatic lesions detected on scintiscans is a common clinical problem. It is usually assumed that radionuclide rapid sequence flow studies and blood pool images are reliable and accurate methods of demonstrating the vascularity of hepatic lesions. Our recent experience with 3 patients with angiographically proven hepatic hemangiomas indicates that radionuclide techniques may fail to detect the vascularity of hemangiomas. We speculate that blood flow within a hepatic hemangioma may be sluggish and its vascularity may be appreciated only by arteriography. Therefore, we alert the clinician to assess the vascularity of solitary hepatic tumors by angiography before percutaneous liver biopsy and thereby avert the possibility of life-threatening exsanguination, as occurred in one of our patients.


[Outpatient termination of pregnancy in the first trimester during paracervical blockade with Carticain (author's transl)]. Sparing termination of pregnancy with a low incidence of complications, using the drainage method in local anaesthesia, can be effected on an outpatient basis. Carticain, which is a rapidacting anaesthetic with good analgesic effect, enables practically painless dilatation of the cervical channel with subsequent evacuation, when combined with good psychological guidance of the patient. When questioned postoperatively, practically all patients were in favor of local anaesthesia. Another positive aspect, in their opinion, was the fact that they could be discharged after brief hospitalization. Furthermore, treatment on an outpatient basis is cost-saving.


[Differential diagnosis of tumors in the pelvis of gynecologic patients by angiography (author's transl)]. The value of angiography in differential diagnosis of tumours of the pelvis is discussed based on 15 cases and the relevant literature. Inflammatory infiltrates and neoplasms arising from the sigmoid colon can be separated from gynaecologic tumours by angiography. In 4 cases with pelvic masses in which differentiation between a myomatous uterus and an ovarian tumour was not possible clinically, unequivocal evidence was cleaned from a selective injection into the internal iliac artery. Angiography is particularly well suited for the delineation of parietal pelvic tumours--especially of vascular malformation.


[Fetal damage due to mushroom poisoning with amanita phalloides during the first trimester of pregnancy (author's transl)]. A 25-year old para II suffered of mushroom poisoning by amanita phalloides at 9 weeks gestation. When the life threatening maternal illness was overcome a therapeutic abortion was carried out at 12 weeks gestation. Prostaglandin F2 alpha was injected retro-amniotically. The damage to the fetus by the toxins of amanita phalloides is described and discussed.


[Seasonal variations in the incidence of the conception of multiple pregnancies in two centuries (author's transl)]. Seasonal variations in the incidence of the conception of multiple pregnancies are compared in the same population area in two centuries. 12,617 singleton and 101 twin pregnancies from 1803 to 1852 are compared to 63,967 singleton, 473 twin and 5 triplet pregnancies from 1965 to 1970. In both groups the percentage decrease of multiple conceptions during the first three months of the year was higher than the percentage decrease of singleton conceptions. In both groups the percentage increase of multiple conceptions during the summer months was higher than the percentage increase of singleton conceptions. The question of the influence of light on the hypothalamic-pituitary centres as a cause of the variations in multiple conceptions is discussed. The incidence of multiple conceptions has decreased since the beginning of the 19th century independant of the progress in obstetrics and perinatology. The decreased rate of multiparas and especially older multiparas is suggested as the likely cause for this decrease.


[The therapy of the hypertensive form of late gestosis (author's transl)]. Based on five cases of intrauterine death associated with preeclamptic toxemia, a possible relationship between the antihypertensive treatment with Catapres and the fatal outcome of the fetus is discussed. Catapres is known to decrease cardiac output and, in addition, diminishes the utero-placental circulation. For effective prevention of hemodynamic failure in such cases, it is advisable to use Catapres only in combination with adequate intravenous infusion therapy. Further investigations concerning this possible relationship should be done to determine sufficiently whether or not Catapres can be used without risk as a hypertensive drug in late gestosis.


[Examination of two sampling methods (pistolet and jet washing) for endometrial tissue (author's transl)]. The Pistolet-Aspiration and Gravlee Jet-Wash Techniques were used to examine 112 patients at random and the efficacy of each technique compared. The Pistolet-Aspiration technique is more often applicable and significantly provides sufficient material for cytologic and histologic evaluation. The histologic diagnosis was compared with the histologic diagnosis of the uteri after hysterectomy in all cases. In consideration of our results, the easier practicability and because of its economy we prefer the Pistolet-Aspiration technique versus Gravlee Jet-Washing. A catalogue of indications for Pistolet-Aspiration is also given in the discussion.


[Inguinal lymph node metastasis as primary symptom of endometrial carcinoma (author's transl)]. Two cases of postmenopausal women with inguinal lymph node metastases of papillary adeno-carcinoma are reported. Enlarged inguinal glands appeared for six months and two years, respectively. The search for the primary tumour site over several months was negative. The existence of an endometrial carcinoma had not been considered, because the symptom of vaginal bleeding was absent.


[Optimation of postoperative prophylaxis of thrombosis in gynaecology (author's transl)]. The prophylactic effect of heparin dihydroergotamine, the combination of these two (Heparin-Dihydergot)  and acetylsalicylic-acid in the prevention of deep vein thrombosis was investigated in a prospective randomized clinical trial involving 454 patients. Evidence of thrombosis was detected by the 125I-fibrinogen-uptake-test in 22 out of 75 patients (29.3%) in the control group. The application of 2 x 0.5 mgDHE or 2 x 5000 IU of heparin reduced the incidence of deep vein thrombosis to 7%, which is statistically significant. After simultaneous prophylaxis with both drugs the incidence dropped to 2%. The combined use of DHE and heparin may be considered the best prophylactic regimen available for lowering postoperative DVT. After application of 3 x 0.5 g of ASS frequency of DVT decreased only to 15.3% and shows poor prophylactic efficacy.


Heritability of quasi-continuous skeletal traits in a randombred population of house mice. Heritabilities of 11 quasi-continuous skeletal traits were estimated in randombred house mice of three separate ages (1, 3, and 5 months). Three separate methods--regression, maximum likelihood correlation, and Falconer's Method--were used to obtain heritabilities for each of the separate age groups. Significant differences in the incidences of seven of the skeletal traits were found among ages, but they did not affect the heritability estimates, these estimates being pooled over ages. Heritabilities calcuated from female parents were consistently higher (by about 13%) than those from male parents, indicating the presence of maternal effects. Mid-parent estimates made by all three methods gave very similar mean levels (0.17--0.20). Although low, this level compared favorably with that expected on the basis of previously estimated rates of accumulation of genetic variance. Maternal effects estimated from full sib correlations averaged 0.08.


Crossover suppressors and balanced recessive lethals in Caenorhabditis elegans. Two dominant suppressors of crossing over have been identified following X-ray treatment of the small nematode C. elegans. They suppress crossing over in linkage group II (LGII) about 100-fold and 50-fold and are both tightly linked to LGII markers. One, called C1, segregates independently of all other linkage groups and is homozygous fertile. The other is a translocation involving LGII and X. The translocation also suppresses crossing over along the right half of X and is homozygous lethal. C1 has been used as a balancer of LGII recessive lethal and sterile mutations induced by EMS. The frequencies of occurrence of lethals and steriles were approximately equal. Fourteen mutations were assigned to complementation groups and mapped. They tended to map in the same region where LGII visibles are clustered.


Recognition sequence of a restriction endonuclease from Haemophilus gallinarum. From comparison of the sequences in and around the cleavage sites of restriction endonuclease HgaI isolated from Haemophilus gallinarum, the recognition sequence and cleavage site of this enzyme was deduced as below: (formula: see text) This enzyme recognizes a specific but asymmetric penta-nucleotide sequence, GCGTC, and introduces staggered cleavages at appointed positions away from the recognition sequence, generating protruding 5'-ends of five nucleotides. The sequences surrounding the cleavage sites bear no obvious relation to one another.


Differential diagnosis of urinary incontinence. Some degree of bladder instability is common in elderly people because aging changes in the portion of the frontal cortex concerned with micturition allow uninhibited bladder contractions. Although this in itself is not a cause of urinary incontinence, it may be an important predisposing factor and must be differentiated from all other causes. Stress incontinence occurs when the bladder outlet becomes incompetent because of weakness of the supporting pelvic muscles. Incontinence also can be a symptom of atrophic urethritis, acute cystitis, chronic bacteriuria, or bladder carcinoma. Overflow incontinence results from retention of urine, which can be caused by impacted feces, prostatic enlargement, autonomic neuropathy, or anticholinergic drugs. A complete history and thorough physical examination, with special attention to neurologic signs, vulval appearance, and rectal examination often will reveal the cause of urinary incontinence. If the cause is not readily apparent, cystometrography is indicated, and if the bladder is normal, cystoscopy should be done immediately. A more limited examination is acceptable only in demented patients who may not be able to cooperate in the examination and subsequent treatment.


Nutrition counseling needs in a geriatric population. The diet of many elderly people is low in essential nutrients, apparently because of the physiologic and psychosocial changes that accompany aging and a lack of nutrition counseling. Many older Americans are also overweight. Others require special diets that modify long-established eating patterns and nutrient intake. A study of nutrition in 680 elderly people showed that demographic variables significantly related to weight were marital status, education, income, and living arrangements. Inadequacy of calcium or vitamin A or C was not affected by marital status. However, living arrangements influenced dietary adequacy of calcium, and income and education affected intake of vitamins A and C. Data obtained in this study showed that subjects both were interested in and needed nutrition counseling; 36% wanted more information on a balanced diet. Nutrition counseling should play a major role in geriatric treatment programs.


When autoimmune hemolytic anemia complicates chronic lymphocytic leukemia. Autoimmune hemolytic anemia often develops in patients with chronic lymphocytic leukemia, particularly elderly women. It is heralded by a drop in the hematocrit, elevation of reticulocytes, development of jaundice, or a rise in the indirect fraction of serum bilirubin. Evidence of hemolysis supports the diagnosis, and a positive result of the Coombs test confirms it. Survival time is considerably shorter in patients who have both diseases than in those with chronic lymphocytic leukemia alone. Presenting symptoms in patients with the two diseases may include weakness, dizziness, fever, or hemorrhagic phenomena. If the anemia is severe, palpitations, otic pulsations, and cardiac decompensation are common. Physical examination may show enlargement of reticuloendothelial structures. On the other hand, some patients may be essentially asymptomatic. The hemolytic process must be treated as a separate entity, as even vigorous treatment of the leukemia often does not control it. Corticosteroid therapy is preferred, with splenectomy as a second line of defense. If the patient is not a good surgical risk, chemotherapy should be considered. Transfusions are usually incompatible but should be risked if progressive congestive failure, neurologic disturbance, angina, or signs of an impending infarct are present.


Evaluating dysfunction of the autonomic nervous system. Simple bedside measurements of blood pressure and systolic pressure response to the Valsalva maneuver will confirm a clinical impression of orthostatic hypotension. Careful questioning of the patient usually elicits other symptoms of autonomic nervous system dysfunction, such as impotence, urinary and fecal incontinence, constipation or diarrhea, blurred vision, or sweating changes. Drugs are the most common cause of autonomic dysfunction, and their benefits should be weighed against the severity of the dysfunction. In addition, diabetes mellitus, uremia, amyloidosis, acute intermittent porphyria, myeloma, tabes dorsalis, and alcohol-nutritional problems may produce symptoms of autonomic dysfunction. Thus, patients who present with autonomic features but no history of dysfunction-producing drugs should undergo complete laboratory evaluation. A regimen of tyramine or L-dopa or a diet rich in cheese, processed meats, and wine (a monoamine), coupled with a monoamine oxidase inhibitor have beneficial effects in patients with orthostatic hypotension due to preganglionic autonomic dysfunction. Patients who do not respond to catecholamine precursors have stable, isolated orthostatic hypotension or a polyneuropathy such as that caused by diabetes.


Direct effect of bile salts and phospholipids on the physical properties of mucus. Reflux of duodenal contents into the stomach has been implicated in the disruption of mucosal defence and the subsequent occurrence of gastric ulcer. The change produced in the rheological properties following the addition of bile salts and phospholipids to mucus samples was used to assess resultant structural changes. Sodium deoxycholate, sodium taurodeoxycholate, sodium glycocholate, and lysophosphatidylcholine decreased both viscosity and elasticity, indicating that structural breakdown had occurred, whereas phosphatidylcholine could not be shown to have any effect. It is therefore suggested that some of the ulcerogenic activity of naturally occurring surfactants may be associated with their ability directly to reduce mucus consistency.


Autoradiographic study of the permeability characteristics of the small intestine. This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: 14C-urea, 3H-mannose, 3H-inulin, and 125I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it is not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier is greater than that of the capillary barrier.


Coeliac disease in Sudanese children.

Coeliac disease in Sudanese children. Coeliac disease has not hitherto been documented in Sudanese children. This report describes seven Sudanese children with coeliac disease of whom two are siblings. They all had evidence of impaired intestinal absorption, severe histological changes of their jejunal mucosa with clinical and histological improvement on gluten free/sorgham free diet. Subsequently one patient had a clinical relapse when gluten was reintroduced; four had positive gluten challenge using serial one hour blood xylose estimation. They all belonged to the upper socioeconomic group of the society in the north of the Sudan.


Cell-mediated immunity to gluten fraction III in adult coeliac disease. A migration inhibition test was used to assess sensitisation of blood leucocytes, and thus cell-mediated immunity, to gluten fraction III in controls and patients with coeliac disease. Migration indices were significantly less (indicating sensitisation) in untreated and in treated patients than in controls, and significantly less in treated patients than in untreated patients. At a concentration of 1 mg/ml gluten fraction III, 13% of untreated patients and 54% of treated patients had migration indices in the sensitised range. At 2 mg/ml gluten fraction III, sensitisation was demonstrated in 8% of untreated patients and 48% of treated patients. After starting a gluten free diet, migration indices fell into the sensitised range in all patients followed. After at least nine months on a gluten free diet, migration indices were significantly higher in those patients with a normal interepithelial lymphocyte count than in those patients with a raised interepithelial lymphocyte count. Cell-mediated immunity to gluten fraction III can be detected in the peripheral blood of certain patients with coeliac disease. Detectable sensitivity is related to the time on a gluten free diet, and the interepithelial lymphocyte count.


Selective angiography in acute mid-gut ischaemia. Acute mesenteric ischaemia has a high mortality. Early diagnosis and treatment appropriate to the type and extent of vascular insufficiency are essential. Selective angiography can establish the diagnosis and distinguish patients with acute vascular occlusion who require urgent surgery from those with non-occlusive ischaemia for which early surgery is contraindicated.


Variability of colonic function in healthy subjects. Twenty healthy subjects eating normal diets made repeated five-day stool collections, the 10 females making their collections in four to six successive weeks. In most subjects there were striking variations in transit time, measured by Hinton's method. The variability of average faecal wet and dry weight, faecal volume, and the frequency of defaecation was equally great, suggesting that the transit time variations were genuine. The size of individual stools varied even more, often tenfold or more. Faecal water content was relatively constant. There were no significant differences between males and females, and in the females there were no obvious changes related to the phases of the menstrual cycle. The normal variability of colonic function should be taken into account in planning experiments and in interpreting existing data.


Comparison of 14C-labelled polyethylene glycol (PEG) with carrier PEG and 14C-PEG alone as a volume indicator in the human jejunum. 14C-labelled polyethylene glycol (PEG) (5 muCi/l) was used as a non-absorbable marker in human jejunum both with and without carrier PEG (5 g/l). Calculation of net water flux was virtually identical whether or not the carrier PEG was included in the perfusion solution. 14C-PEG alone is a satisfactory non-absorbable marker for perfusion studies in the human jejunum.


Treatment of HBsAg-positive chronic active hepatitis with human fibroblast interferon. Two patients with HBsAg positive chronic active hepatitis have been treated with human fibroblast interferon 10(7) units daily for two weeks. Before treatment, both patients had high levels of hepatitis B surface antigen, core antibody, and DNA-binding antibody in the blood and one patient had a fourfold rise in serum AST. During treatment there was a striking fall in the core antibody titre and also in the DNA-binding antibody, which has been maintained for several months subsequently; in one patient the initially high AST level fell to normal. No significant adverse effects occurred, and these observations should encourage further trials of fibroblasts interferon in hepatitis B.


Duodenal bile acid conjugation patterns and dietary sulphur amino acids in the newborn. Patterns of glycine and taurine conjugation of bile acids in duodenal juice have been studied in 20 low birth weight babies at 12 and 22 days of age. They were fed from birth on one of three feeds containing different amounts of taurine and its precursors, cysteine and methionone. Taurine conjugation predominated in those fed on human milk throughout the first three weeks of life. In those fed on SMA or S26 infant feeding formulae, both of which contain very little taurine, concentrations of glycine conjugates were found to exceed those of taurine conjugates by the 12th day. The low glycine-taurine conjugate ratios previously described in newborn babies are, therefore, probably related to the taurine content of the milk which they received. Glycine-taurine conjugate ratios less than 1.0 occur in breast fed infants during the first three weeks of life.


Lower oesophageal sphincter response to gastrin--pharmacological or physiological? The response of the lower oesophageal sphincter (LOS) to intragastric instillation of protein was assessed in 10 healthy volunteers. Sphincter pressures were measured by a rapid pull-through technique and serum gastrin concentrations during each test were determined by radioimmunoassay. Despite stimulation of gastrin release by protein instillation, no significant change in LOS pressure was observed. However, intravenous pentagastrin (0.25 and 0.5 microgram/kg) produced an immediate increase in sphincter pressure, which then returned to the basal level within four minutes. Thus, although pentagastrin is an effective pharmacological stimulant of the sphincter, endogenous gastrin appears not to be a physiological determinant of LOS pressure in man.


Selection of patients for bile diversion surgery: use of bile acid measurement in fasting gastric aspirates. Eighteen patients with dyspepsia and vomiting which followed surgery for peptic ulcer have completed a study to examine the role of diverting bile from the stomach by a Roux-en-Y procedure. Bile regurgitation and mild epigastric pain relieved by vomiting were abolished. Measurements of bile acids in the fasting gastric aspirate were useful in predicting the outcome of surgery; good results were obtained when initially there was reflex into the stomach of more than 120 mumol/hour of bile acids. A wider group of patients than those selected in previous series may benefit from this operation, as good results can be obtained in patients with dyspepsia relieved by alkali and without achlorhydria or gastritis. Endoscopy was repeated one year after Roux-en-Y operation. Erythema of the mucosa was improved, but gastritis did not improve.


Measurement of bile acids in fasting gastric aspirates: an objective test for bile reflux after gastric surgery. We measured the concentration of bile acids in gastric aspirates from patients who had had operations for peptic ulcer. Some patients were asymptomatic and some had postoperative symptoms of the type that have been attributed to duodenogastric reflux. Samples were obtained via a nasogastric tube when the patients were fasting, after food, after pentagastrin, and overnight. We related the concentration and amount of bile acid and the volume aspirated to the presence or absence of symptoms and compared the results with radiological and endoscopic assessments of duodenogastric reflux. The most useful index to discriminate between symptomatic and asymptomatic patients was the amount of bile reflux in half an hour's aspiration from the fasting stomach; this we have termed 'fasting bile reflux' (FBR) and expressed as mumol bile acids refluxing/hour. A figure greater than 120 mumol/h was present in 17 of 22 symptomatic patients and in all who complained of bile regurgitation or bile vomiting. The FBR was less than 120 mumol/h in all of 20 asymptomatic patients, although some of them had reflux detected radiologically and endoscopically.


Serum prolactin in liver disease and its relationship to gynaecomastia. Serum immunoreactive prolactin was measured in 150 patients with liver disease of varying aetiology and severity and in 45 control subjects. The upper limit of the reference range for serum prolactin was 331 mU/l. Eighteen patients with liver disease (12%) had unexplained hyperprolactinaemia. No relationship existed between the prolactin value and the sex of the patient, the aetiology of the liver disease, the severity of the liver disease, or the presence of gynaecomastia. The cause of the hyperprolactinaemia in patients with liver disease and its clinical implications need further investigation.


Exocrine pancreatic secretion and immunoreactive secretin (IRS) release after intraduodenal instillation of bile in man. Six subjects with a normal endoscopic pancreatogram were investigated after an overnight fast by means of a side-viewing duodenoscope. After cannulation of the main pancreatic duct, juice was collected in five-minute samples for 20 minutes. An iso-osmolar solution of 6 g cattle bile was then infused into the duodenum through a separate catheter attached to the outside of the duodenoscope, and pancreatic juice collected in five-minute samples for another 20 minutes. Blood was frequently drawn from an arm vein through an indwelling catheter for estimation of immunoreactive secretin (IRS) by radioimmunassay. The flow rate of pancreatic juice and outputs of bicarbonate, amylase, and protein increased significantly after intraduodenal infusion of bile. A significant rise in plasma IRS was also found after instillation of bile in the duodenum.


Lymphocytotoxicity test against rabbit hepatocytes in chronic liver diseases. We have studied the cytotoxicity against rabbit liver cells of lymphocytes from the peripheral blood of 71 patients with various liver diseases. The group with chronic active hepatitis and three patients with acute alcoholic hepatitis showed significantly higher mean values of lymphocytotoxicity (P less than 0.001) compared with the other patients with chronic persistent hepatitis, post-necrotic fibrosis and cirrhosis. Wilson's disease, and prolonged viral hepatitis. The mean cytotoxicity of these last groups did not differ significantly from controls. In four out of six patients with chronic active hepatitis a significant decrease of lymphocytotoxicity was found after immunosuppressive therapy with oral prednisolone. A good correlation between the lymphocytotoxicity test and histological signs of activity suggests that a cell-mediated immune aggression is present in this disease.


Effect of continuous jejunal perfusion of elemental and complex nutritional solutions on pancreatic enzyme secretion in human subjects. Pancreatic secretion of lipase and chymotrypsin in response to elemental diets and a crushed food homogenate was studied in normal subjects. The solutions were infused at constant flow rates at the ligament of Treitz with polyethylene glycol as a nonabsorbable marker. A triple lumen tube was used, enabling collection of secretions at 35 and 70 cm from the infusion point. The results show that a crushed food homogenate has a greater stimulative effect on pancreatic enzyme secretion than the elemental solutions and that this can be directly related to its greater nitrogen content. The osmolality of the infused solutions does not appear to be important. The relative merits of the solutions tested and total parental nutrition in reducing pancreatic enzyme secretion are discussed.


Nitrite studies in oesophageal cancer.

Nitrite studies in oesophageal cancer. As nitrate consumption may have considerable importance for the in vivo formation of nitrites and potentially carcinogenic N-Nitroso compounds, we have studied salivary nitrite levels in patients with oesophageal cancer and adult volunteers before and after administering 100 ml beet juice containing 160 mg nitrate. Initial salivary nitrite levels were slightly lower in the cancer patients, perhaps because of previous malnutrition. In both groups there was a marked increase in salivary nitrite levels 90 minutes after ingesting beet juice and the attained levels in the two groups were similar. The results imply that formation of salivary nitrite is highly dependent on exogenous dietary nitrate and that there is no difference in the capacity to form nitrites between oesophageal cancer patients and healthy adult subjects.


Increased sensitivity of gastrin release to adrenaline in duodenal ulcer. Serum gastrin concentrations were measured in patients with duodenal ulcer and controls before, during, and after one-hour intravenous infusion of various doses of adrenaline (0.12 microgram to 6 microgram/min). Gastrin concentrations in the basal state were significantly increased in duodenal ulcer patients compared to controls. The maximal rise in serum gastrin concentrations was obtained at a dose of 4 microgram/min adrenaline in both groups of subjects, and the increase was significantly higher in duodenal ulcer patients than in controls. Adrenaline increased predominantly the gastrin III component (gastrin-17 like) in both duodenal ulcer patients and controls. The threshold level of adrenaline-induced gastrin release was significantly lower in duodenal ulcer patients: intravenous infusion of adrenaline in a dose of 0.12 microgram and 0.25 microgram/min increased serum gastrin concentrations 23 and 43%, respectively, but had no effect in controls. Rises in plasma adrenaline concentrations were similar in both groups of subjects in response to the various doses of adrenaline employed. Only the smallest dose of adrenaline (0.12 microgram/min) resulted in clearly physiological variations in plasma adrenaline concentrations. The results indicate that endogenous adrenaline may stimulate the secretion of gastrin during physiological conditions in patients with duodenal ulcer.


Calcium carbonate in human gallstones and total CO2 in bile. Measurement of total CO2 concentrations in bile from patients undergoing cholecystectomy because of gallstones has shown that the presence of calcium carbonate in the stones can be associated with a raised total CO2 concentration in the common duct bile. In bile from functioning and poorly-functioning gallbladders, total CO2 was nearly always related to pH irrespective of stone composition.


Serum and faecal lysozyme in inflammatory bowel disease. Lysozyme (EC 3.2.1.17) concentrations were measured in the serum and stools of patients with inflammatory bowel disease and compared with the concentrations in similar material from normal controls, patints with non-inflammatory gastrointestinal disease, and patients without gastrointestinal disease. By the turbidometric method, values of lysozyme (microgram/ml +/- SD) are considerably greater in the serum of patients with active Crohn's disease (9.2 +/- 2.7) than in the serum of healthy controls (4.4 +/- 2.0). They do not, however, distinguish individual patients with Crohn's disease from those with ulcerative colitis nor from those with a variety of other gastrointestinal conditions. The lysoplate method gives much higher values for serum lysozyme than the turbidometric method but there is a considerable overlap between the results for patients with Crohn's disease (60.1 +/- 30.7) and normal controls (27.4 +/- 17.5). There is only a moderate correlation between the results given by the two methods (r = 0.56) and it is suggested that factors other than enzyme activity and methodological variation are responsible for the observed differences. This is supported by the finding that, with Crohn's disease in remission, serum lysozyme values (lysoplate) return to normal values but with the turbidometric method remain raised. Mean faecal lysozyme levels, expressed either as a concentration or as total daily excretion, in patients with inflammatory bowel disease are very significantly greater than values in healthy controls and in diseased subjects without diarrhoea but are not significantly different from those subjects with other causes of diarrhoea.


Digestion of native collagen in the gut. The digestion and absorption of collagen, native and artificially cross-linked, has been examined in the rat and the Gaboon viper, by feeding known quantities and measuring the hydroxy-proline content of the faeces and of the contents of the gut at different levels, and comparing with an unabsorbable marker (polyethylene glycol). Incubation of collagen in vitro with pepsin at 37 degrees C at pH 1.5 followed by trypsin or chymotrypsin converted about 40% into dialysable material.


Use of ERCP in the diagnosis of internal pancreatic fistula. Two cases of internal pancreatic fistula, causing pancreatic ascites, were demonstrated by the use of ERCP. This new technique is a useful way of establishing the diagnosis, and treatment may in the future be determined by the ERCP findings.


[The atrial sound over the carotid artery]. The appearance of carotid atrial sounds has been observed in 6 out of 19 patients with stroke. It is assumed that these patients have obstructions in the carotid-subclavian area. Further studies to prove this working hypothesis are in progress.


["Grading" and "staging". Significance for clinical oncology]. "Grading" and "staging" means histological classification of tumors, determination of the histological grade of malignancy, clinical and, if possible, surgical-evaluative or postoperative pathological TNM classification and stage classification of tumor patients. Grading and staging are necessary for prognosis, for evaluation of diagnostic standard, for statistical analysis of end results and for therapeutic decisions. The prerequisites for a modern cancer therapy are meticulous histological examination, exact morphological classification of tumor extension, and histological grading of tumors. Therefore, today's pathologist not only diagnosis cancer but also he has an important responsibility in determining the methods of cancer therapy in each individual patient.


The identification of sympathomimetic amines by Raman spectroscopy. This study was undertaken to explore the feasibility of using Raman spectroscopy as a means of identifying drugs in the forensic laboratory. Raman spectra of a group of sympathomimetic amines, in pure form and in pharmaceutical preparations, were obtained and compared; group similarities and individual differences were found, and satisfactory identifications could be made. Water solutions as well as solids were examined. The procedure is rapid, sensitive, simple, and non-destructive.


[Insane offenders. Forensic psychiatry and criminal jurisprudence]. Care and treatment of mentally abnormal offenders constitute a special problem for the traditional penal system as well as for conventional psychiatric services. Persons who are not responsible for their criminal acts need more rather than less security. In this paper 348 criminal offenders were analyzed according to type of offence and diagnosis. This population constitutes 3.11% of all psychiatric in-patients in Austrian psychiatric hospitals. In order to improve possibilities of research and at the same time make custody and release better manageable it is suggested to establish special institutions for mentally abnormal offenders. Special attention is also paid to the problem of suicide and self-injuring of prisoners and especially to personality changes ("functional psychosyndrome") due to chronic imprisonment in cases of long-term criminal inmates.


[Objective criteria for the evaluation of the vocal function]. In search of an objective method for the evaluation of vocal function it was investigated, whether there exists a relationship between the capability of kinesthetic phonatory control, i.e. the operational efficiency of the neuromuscular phonatory control system, and the quality of vocal function. In three groups of subjects with different quality of vocal function (singers, normal subjects and dysphonic patients) pitch and intensity changes of the speaking and singing voice during interruption of auditory feedback (by means of binaural maskings) were measured by means of fundamental frequency analysis. Results showed a much better kinesthetic control ability in singers than in normals and especially in dysphonic patients thus revealing, that the measurement of this ability can be used for evaluating individual vocal function objectively. The main evaluation criteria are: the degree of vocal pitch elevation while speaking under masking conditions, the accuracy of the singing voice without auditory control and the width of pitch perturbations of a sustained voice.


[Polyneuropathy, adrenal insufficiency and diarrhea of unknown origin]. Clinico-pathological conference concerning a syndrome, characterized by considerable diagnostic problems. Polyneuropathy, adrenocortical insufficiency and diarrhea without typical changes in laboratory or functional data should always lead to the suspicion of primary amyloidosis. This diagnosis could be confirmed in the discussed case report. Its clinical relevance in regard to the type of spreading--perireticular or pericollagenous--is discussed, methods for identification are mentioned.


[The oral application of berotec in the therapy of obstructive airway diseases]. The intensity and duration of action of Berotec (fenoterol) syrup in doses of 2.5 mg and 5.0 mg were investigated in an acute cross-over study in comparison with placebo, using the double blind technique. By measurement of the forced expiratory volume (FEV1) and the forced expiratory flow rate (FEF200-1200) significant improvement in pulmonary function could be detected from 1 to 4 hours after administration of 2.5 mg and from 1 to 8 hours after administration fo 5.0 mg Berotec syrup. The intensity of action exhibited a statistically significant dose dependence and was greater after the 5.0 mg dose (p=0.05) than after 2 puffs from Berotec metered aerosol taken by the patients in a pre-test. Minor side effects were observed in 2 cases: in one patient on the 5.0 mg dose they were clearly sympathomimetic and accompanied by a stronger bronchodilating effect.


[Glucose-6-phosphate dehydrogenase deficiency of the mediterranean type B minus. 2. Etiological basis for severe hyperbilirubinemia in the newborn]. After having described in detail the pathophysiology, symptomatology, X-chromosomal inheritance and some laboratory methods in detecting G-6-PD-deficiency by demonstrating a case of favism (Schulz et al. 1977), the authors now discuss the particularities of the enzyme deficiency in the newborn. These are complicated by additional physiological and transient deficiency of the enzymes catalase, NAD-diaphorase, glutathione peroxidase, and glucuronyl transferase. Several chemical substances, acidosis, hypoxia, hypoglycemia, and immaturity may cause a severe hyperbilirubinemia in G-6-PD-deficient newborns. The development of a kern-icterus in these cases may be prevented by early exchange transfusion. From clinical findings and some observations in different regions of Greece an additional factor influencing the liver function has been postulated which favors the development of hyperbilirubinemias in G-6-PD-deficient newborns. The nature of this possible factor is discussed. The authors emphasize the necessity of screening for G-6-PD-deficiency during pregnancy in families of mediterranian descent.


[Increased insulin secretion in dystrophia myotonica]. Serum insulin levels were determined in patients with myotonic dystrophy after intravenous administration of glucose and were found to be higher than in control persons in about 60%. Although several interpretations of this observation are possible we favor the assumption, that an increased sensitivity of the insulin producing system of the pancreas is the reason. With regard to the most accepted hypothesis that myotonic dystrophy is a disorder due to impaired membrane function, it is tempting to explain our findings by an altered membranal function of the insulin producing cells, too.


[Cerebro-organic syndrome during gold therapy. Possible correlation between gold therapy in chronic seronegative polyarthritis and the appearance of a cerebro-organic syndrome. A case contribution]. In this article the possible relationship between gold therapy of a chronic seronegative polyarthritis and the appearance of a cerebro-organic syndrome in a 56-year-old postmenopausal woman will be discussed. We take into consideration the basic illness, the biography, the hormonal situation, the simultaneous chloroquin therapy and the overdosage of the gold drug. After a careful consideration of the different diagnostical possibilities following the above mentioned factors, not only a temporal but also a causative relationship of gold therapy and cerebro-organic syndrome seems to be possible.


[Evaluation of the central venous pressure as a measure for fluid and volume therapy]. Pulmonary capillary wedge pressure more accurately reflects left ventricular function than does central venous pressure. However, left ventricular function is the best measure for peripheral perfusion and, therefore, for adequate fluid volume therapy. In only 13 out of 32 patients monitorized by Swan-Ganz catheter we found a correlation among central venous pressure and pulmonary capillary wedge pressure. Studying the histories of the group without correlation we found significant cardiac and pulmonary diseases. Therefore, if central venous pressure is used for monitoring of fluid volume administration the history and physical findings of the pulmonary cardiac system have to be strictly considered. Sharp rises of the central venous pressure after small amounts of fluid intake carry the risk of pulmonary edema.


[Stimulation of hepatic gluconeogenesis from amino acids in acute uremia]. Investigations on the role of alterations in hepatic carbohydrate metabolism in so-called pseudodiabetes of uremic subjects are reported. All experiments were carried out in acutely uremic rats produced by bilateral nephrectomy. The results are summarized in Fig. 5. From this follows that by some still unknown mechanism an altered hormonal equilibrium seems to develop. From a stimulation of endogenous hepatic proteolysis, acceleration of amino acid transport into the liver cell, and activation of L-serine-dehydratase and other key enzymes of amino acid metabolism, an increased supply of substrate for gluconeogenesis can be expected, thus leading to enhanced formation of glucose by the liver in acute uremia.


[The diagnostic efficiency of tonography]. There are three methods for increasing the diagnostic efficiency of tonography: The improvement of tonographical technique, the combination of tonography with provocative tests and methods of mathematical differentiation. Our own bulbar-compression isotonographical method is described. This method allows a choice of different pressure gradients. Our method was applied to 28 normal and 40 glaucomatous eyes. This method was carried out twice on all patients using two pressure gradients: Pt = Po + 30 and Pt = Po + 10. Also, the outflow facility (L) was determined by Grant's tonography. Thus, 3 L-values were obtained with 3 varying pressure differences (Pt -- Po = deltaP). With this differential tonography the mathematical determination and the graphic representation of a real L-value (Ldiff) by deltaP = 0 are possible. With normal eyes the average L-values were indirectly proportional to the pressure differences. This relationship was found to be directly proportional to glaucomatous eyes. The tonographical coefficients Po/L, P3/L3-7,Po -- 10/L and Po/Lintegral were calculated on 104 normal and 312 glaucomatous eyes. The diagnostic efficiency of tonography is increased by the determination of Ldiff (percentage of positive values = 70%) and the calculation of Po/Ldiff value (95%).


[The value of the radio-allergo-sorbent test (RAST) in the diagnosis of pollinosis]. Conclusions for pollinosis: 1. RAST is not necessary for the diagnosis when history and skin tests are characteristic. 2. If RAST is indicated (e.g. small children, urticaria factitia, eczema) tests with two or three grasses or a grass-mixture are sufficient. 3. RAST classes 1 and 2 have no diagnostic value. 4. If skin tests give no clearcut results provocation tests are preferable to RAST.


[Corpus carcinoma and myomatous uterus. Incidence and course during the last 25 years]. The incidence of carcinoma corporis uteri and myoma uteri in the last 25 years was studied. The number of carcinoma of the uterine body is increasing in relation to other gynaecological cancers. Most cases occurred in the 6th and 7th decade of life. Small uterine cavities (up to 7.5 cm) and uterine weight of less than 100 grams show increasing frequency. The incidence of cavities larger than 10 cm and uteri weighing more than 200 grams is decreasing. The uterine cavity was in 47% larger than 9 cm. Uterine weight was more than 100 grams in 46% of the cases.


[Nuclearmedical tumor diagnosis].

[Nuclearmedical tumor diagnosis]. Nuclear medicine diagnosis is an important discipline in cancer searching. By using reliable radiopharmaceuticals practically all organs can be investigated, especially bone cancer.


[Treatment of severe lung embolism under conditions of reanimation]. Despite intensive conservative treatment a 35-year-old woman with massive pulmonary embolism and cardiogenic shock developed cardiac arrest. After 45 minutes resuscitation, mechanical heart action reappeared with a systolic blood pressure at 60 mmHg. Though cardiogenic shock persisted, the patient survived operative embolectomy without any damage. Presenting this case as well as newest clinical reports, the chances of treatment of acute massive pulmonary embolism, conservative or operative, are discussed.


[Drug therapy of shock].

[Drug therapy of shock]. Shock is to define by clinical symptoms, measurable haemodynamic and metabolic changes, clotting failure and disorders of fluid, electrolyte and acid-base balance. It is essential to remove hypovolemia, acidosis, cardiovascular failure, pulmonary and renal insufficiency. Quite a lot of proved and controversial pharmacological substances are placed at physician's disposal. However, the mortality of cardiogenic shock and gram-negative septic shock is more than 80% respectively 30%, often caused by shock lung or irreversible injury to the kidneys. Shock due to depletion of extracellular fluid, poisoning and acute pancreatitis require specific treatment.


[Biochemical and pharmacological properties of new 2-substituted aziridines. Contribution to experimental tumor research]. A new class of compounds, the 2-cyanaziridines, has immune-modulating properties. This immune-modulation was proved by the influence on the delayed type hypersensitivity reaction, the increase of the lymphocyte transformation by T-cell-specific mitogens ConA and PHA, the increase of phagocytosis of macrophages, the increase of resistance against bacterial, fungal and virus infections and by the influence on various transplantation tumors in mice and rats.


[Immune status after tetanus vaccination. Possibilities and indications for a quantitative rapid determination of tetanus antibodies in human serum]. Active and passive immunization against tetanus is one of the most used vaccination procedures in our population. Detection of size and duration of protection till now failed due to expensive methods. Counter-Immuno-Electrophoresis (CIE) is presented as a simple and non-expensive method with adequate sensitivity, and allows to obtain data concerning immunity of tetanus-immunized persons in almost any case. Rarely positive results as to antitoxin level are obtainable only by more sensitive methods. Further detection methods, and examinations of tetanus-immunity of "problem patients" showing immunofailure and of collectives immunized on various schedules will be reported later.


[Will Salk's polio vaccination be used again?]. The value and special problems of application of killed and life polio vaccines are compared and discussed. The vaccination with life polio vaccine will be continued generally. Killed polio vaccine may be useful in children with immunodeficiency only.


[Therapy for cholelithiasis].

[Therapy for cholelithiasis]. It is recommended that elective cholecystectomy for cholelithiasis be performed right away after the first colic. This decreases the operative mortality to 0.3-1.0%. 2. The occurrence of local complications leads to a ten-fold increase in mortality. 3. Patients with gallstones but without symptoms should be operated during their 5th decade of life because half of these patients will later on develop serious symptoms and 25% even critical local complications requiring surgery. Operative mortality in the old age group, however, is considerably higher at 7-20%. 4. The acute cholecystitis should nowadays be treated by surgeons because early operation usually results in an operative mortality of as low as 1-1.5%. 5. The postoperative treatment of choice for residual common duct stones is either chemical dissolution via the T-tube extraction via the T-tube canal or endoscopic retrograde extraction of the stone after papillotomy. A reoperation is indicated only in the rare event that these methods should fail.


[Clinical aspects of a new, very low dose combination contraceptive]. In a multicentre trial in Yugoslavia 150 fertile women were treated during 2541 menstrual cycles with Ovoresta M, a new low-dosed combined oral contraceptive pill. Each tablet contains 0.75 mg lynestrenol and 0.0375 mg ethinyloestradiol. Evaluation of the results shows that there were no pregnancies. Irregular bleedings occurred in 8.1% of all cycles. The side effects recorded were mainly due to the fact that for 140 of the 150 participants this was the first oral contraceptive they ever used. 2 women dropped out for relevant reasons (irregular bleedings). Because of the low dosage of active ingredients the authors consider Ovoresta M a welcome supplement to the existing oral contraceptives.


[Prostatectomy incontinence].

[Prostatectomy incontinence]. Urinary continence is guaranteed by the system of smooth urethral musculature, the so-called sphincter internus. The striated sphincter externus has primarily no responsibility for continence. One of its most important functions is the initiation of a voluntary micturition. Further functions are: the voluntary interruption of the urinary stream, the reflectory occlusion by elevated intraabdominal pressure (coughing, sneezing, laughing, heavy physical work), expression of the rest of urine in the urethra after micturition, stabilization of the proximal urethra in the urogenital diaphragm. To get an optimal function after prostatectomy an intact sphincter externus becomes important for the smooth urethral muscular system which is further responsible for the continence. About 90% of all patients with a postprostatectomy incontinence have an intact sphincter externus. In these cases we have a high incidence of incontinence cure. Only in 10% of incontinence after prostatectomy the sphincter externus is damaged. In those cases the incontinence operation is inadequate.


[Studies on the estimation of the postmortem interval. 2. The postmortem lividity (author's transl)]. The authors have investigated the relationship between the postmortem interval and the postmortem lividity of 430 persons who had died at known times and had been subjected to medico-legal autopsies. 1) For determining the postmortem interval from the postmortem lividity, the examination of the fading of the lividity upon pressure is most reliable. Among various methods of pressing, the pressing by means of a narrow side-edge of a hard instrument such as a pincette offers more accurate results than those by means of the fingerpressure which is commonly adopted in the present medico-legal practice. 2) The rate of nonfading is higher in summer among the cadavers within 6-12 hours after death, while over 12 hours it does not show any seasonal variation. Considering the influence of the cause of death, death by asphyxia and death by intracranial injuries show lower nonfading rate than death by exsanguination and natural death. These differences are observed merely within 24 hours after death. 3) Nonfading occupies one-third of cases during 6-12 hours after death and exceeds a half during 12-24 hours and exceeds two-thirds during 1-3 days and occupies almost all cases over 3 days. Namely, complete fading is observed within 3 days after death.


Studies on the estimation of the postmortem interval. 3. Rigor mortis (author's transl). The authors have devised a method for classifying rigor mortis into 10 types based on its appearance and strength in various parts of a cadaver. By applying the method to the findings of 436 cadavers which were subjected to medico-legal autopsies in our laboratory during the last 10 years, it has been demonstrated that the classifying method is effective for analyzing the phenomenon of onset, persistence and disappearance of rigor mortis statistically. The investigation of the relationship between each type of rigor mortis and the postmortem interval has demonstrated that rigor mortis may be utilized as a basis for estimating the postmortem interval but the values have greater deviation than those described in current textbooks.


Macroscopical observations on a human anencephalous fetus with multiple malformations (author's transl). The present report treats a female stillborn human anencephalous fetus with the craniorrhachischisis, cleft palate, left-sided congenital diaphragmatic hernia, hypoplasia of lungs, imperforate vagina and anus, absent left kidney and sternal muscle on the left side. In view of the rarity of the records of autopsied cases of anencephaly, authors made efforts to obtain informations on how all the organs in this fetus and their topographical relation in each other are affected by the anencephaly. The findings are summarized as follows. 1) This case falls under Anencephalus craniorrhachischisis in NANAGAS (1925)'S classification. 2) The greater part of thoracic and lumbar vertebral column except T10, 11, 12 and L1 segments shows several segmental malformations. The lumbar vertebral column is twisted towards right and the left posterior abdominal wall is nearly absent. Due to these changes, only two ribs are present on the left side. 3) In this case, there is a congenital diaphragmatic hernia through persistent left sided pleuroperitoneal canal. The abdominal viscera protruded into the pleural cavity are the caecum, vermiform appendix, colon, spleen and pancreas. 4) On both sides, the ventral rami of the thoracic, lumbar and sacral nerves are normal in number. Their spinal ganglia situated on these nerve roots are, however, fused to form eight ganglionic masses. 5) The five short left thoracic ventral rami arise from a ganglion lying on the posterior thoracic wall. This ganglion gives off the two branches communicating with the right 7th, 8th and 11th thoracic nerves. On the other hand, the right lumbar plexus receives the left 1st, 2nd and 3rd lumbar nerves. In the left pelvic part, there is another ganglion which gives off the two large branches to the right 1st and 2nd sacral nerves. 6) From the findings mentioned above, it is advisable to examine not only the ectodermal structures but also mesodermal ones to promote the studies on a factor in the genesis of anencephaly.