[Anatomically corrected malposition of the great arteries (author's transl)].

Anatomically corrected malposition of the great arteries is defined as a trunco-conal malformation characterized by an aorta arising anteriorly from a morphologically left ventricle and by the presence of a subaortic muscular conus. This malalignment determines a conotruncal-ventricular discordance: d-loop and l-position or l-loop and d-position of the aorta. Two additional cases of this very rate lesion are reported, both associated with left juxtaposition of the atrial appendages, tricuspid atresia, ventricular malrotation and destrocardia in situs solitus with d-loop. Because of the high frequency of this association, observed also in the majority of the previously published cases, its morphogenetic significance and implications are discussed.


[Behaviour of blood digoxin, determined by the radioimmunity method, in patients with renal failure (author's transl)].

The authors used radioimmunity to study blood digoxin behaviour in patients with normal renal function and with variable BUN. The computerized and mathematically considered data showed that digitalic intoxication occurs with higher digoxin blood levels in patients with renal failure than in normal renal function cases. In the first case, moreover, it occurs sooner than in the second one, and the total digoxin dose is smaller than in normal patients. We have found that the large range of digosin blood levels is vital in deciding the therapeutic and toxic dose; that may be done, for most cases, following the estimate of the theoretical saturation dose using our method.


[Behaviour of left ventricular systolic time intervals after isometric exercise in patients with ischemic heart disease (author's transl)].

The authors describe differences in behaviour of left ventricular systolic time intervals after isometric exercise between patients with ischemic heart disease and normal control. Isometric exercise consists of tonic hand-grip, which is to be gauged by hand-grip dynamometer for 5 minutes at 30% of the patient's maximum voluntary contraction or for 2-3 minutes at 50%. The parameters referred to are pre-ejection period and left ventricular ejection time index (PEPI, TETI), the PEP/TET ration, heart rate and arterial pressure. The authors conclude that from isometric exercise it is possible to point out the heart failure degree in patients with ischemic heart disease.


[A study of segmentary arterial blood pressure in the evaluation of obstructive arteriopathy of the lower limbs (author's transl)].

The pressure segmentary systolic blood pressure of lower limbs is described in normal and arteriopathic subjects. After reviewing the various methods currently used, the authors emphasize the diagnostic value of ankle/arm pressure index and segmentary gradient. The limits of the method are also discussed. The changes in ankle pressure after exercise are then considered, as a noninvasive useful technique in the functional evaluation of obstructive arterial disease in the lower limbs.


[Long term treatment of familial hypercholesterolemia with Colestipol, a new anionic exchange resin (author's transl)].

Results relative to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolemia, 12 with Type II A, 8 with Type II B and 3 homozygotes are reported. The patients had previously undergone treatment with clofibrate together with a hypocholesterolemic diet. After six weeks with placebo, the patients were given 15 g/die active drug for a period of 12 months and a double dose (30 g/die) for a successive period of 4 months. During the experimental trial the same hypocholesterolemic, isocaloric diet which had been followed during the previous hypolipidemic treatment was maintained. In the entire group taken as a whole, the total mean decrease was --56,9 +/- 15 mg/dl (P less than 0,01) after 12 months of 15 g/die Colestipol and --62,8 +/- 13 mg/dl (P less than 0,01) during the following 4 months with 30 g/die Colestipol. The difference between the two periods of treatment (15 g and 30 g/die) is not statistically significant. During the active drug treatment a slight but not statistically significant triglyceride increase was observed. The increase was most marked in the Type II B patients: the triglyceride variations in this group could be partly caused by slight variations in mean body weight. Starting from a mean basal value of 3,9 +/- 0,2 mg/dl, serum uric acid showed a significant increase which was maintained throughout the entire period of treatment, reaching a peak of 5,6 +/- 0,3 mg/dl (P less than 0,001) at the twelfth month. During the experimental trial no significant modifications were observed in the hematological routine analysis and liver functional tests, no malabsorption syndrome and no signs of toxicity were seen. Most frequent side effects were constipation, nausea, metheorism which, with the exception of four cases, which were withdrawn from the study, were reported as being transitory and mild. In conclusion, since Colestipol treatment significantly lowers cholesterol levels in patients with familial hypercholesterolemia and does not manifest any toxicity or serious side effects, it can be used effectively in the long term treatment of this disease which is characterized by an elevated frequency of cardiovascular complications.


[Intra-aortic balloon counterpulsation: first clinical experiences (author's transl)].

Three cases of acute myocardial infarction treated with intra-aortic balloon counterpulsation (IABP) are reported. In the first patient cardiogenic shock and pulmonary oedema were the complicating features; the second one had pulmonary oedema refractory to medical treatment. Both patients promptly improved, shock and heart failure having been reverted to clinically satisfactory conditions. Nevertheless the first patient could not be weaned efficiently and died on the sixth admission day. A huge myocardial involvement was found autoptically. The second patient died on the third day mainly because of a haemorrhagic complication. The third patient started the treatment with IABP at the 68th hour because medically unresponsive left heart failure and persisting ECG signs of widespread myocardial ischemia. Improvement of haemodynamic parameters and disappearance of subepicardial lesion were achieved. Eventually this patient was discharged on the usual rehabilitation regimen.


[Phono-mechanographic surveys of a patient with Björk mitral valve prosthesis and complete atrio-ventricular block (author's transl)].

A study of a patient with Björk-Shiley mitral valve prosthesis and complete artrio-ventricular block recorded the presystolic valve closure with -r intervals equal to or higher than 290 m.sec. After applying a permanent pacemaker, closure of the prosthesis of the presystole occurred when the atrial systole preceeded the spike by at least 190 m.sec. This survey demonstrates that the atrial systole can provoke, by itself, the closure of the mitralic valve.


[Surgical correction of a case of valsalva sinus aneurysm and aortic insufficiency caused by salmonella typhi (author's transl)].

The authors describe a case of aneurysm of the non-coronary sinus of Valsalva and aortic insufficiency caused by Salmonella Tiphi in a 7 year old child. The exceptional ethiology is discussed as well as the problems connected with surgical correction.


[Coronarographic evaluation of dystrophic cardiomiopathy (author's transl)].

A 22 year old man with Duchenne's progressive muscular dystrophy is presented. Because of electro-and vectorcardiographic features compatible with ischemic heart disease, coronary angiography was performed in order to rule out obstructive coronary disease, which has been excluded in our case. The coronary tree presented the same characteristics of idiopathic primitive cardiomyopathy. The authors assert that the coronary arteriography is a necessary complement to the diagnosis of Duchenne's muscular dystrophy.


[The association between primitive pulmonary hypertension and essential systemic arterial hypertension. Remarks on two personal observations (author's transl)].

The clinical, laboratory, haemodynamic, cardioangiographic and anatomo-pathological features are described in two patients in whom the association of "Primary Pulmonary Hypertension and Arterial Essential Systemic Hypertension" was noticed. On the basis of a hyperactive neurohormonal mechanism, a hypothetical, ethiological relationship between the pure hypertensive state of both the circulations is discussed. The occurrence of hypertensive systemic episodes and Raynard's phenomena lend weight to the hypothesis that neurohormonal mechanisms might participate in the pathophysiology of this syndrome.


[Self-measurement of blood pressure in hypertensive patients. A psychological study (author's transl)].

Risks and complications of arterial hypertension can be reduced by an active and prolonged treatment. However, only a small number of hypertensive subjects is treated effectively. The co-operation of patients in the management of the disease may be useful in the treatment of hypertension. The authors report the results of a study of thirty hypertensive patients chosen at random, who checked their arterial pressure by themselves. The psychological reactions, the advantages and disadvantages of this experience and the attitude of the attending physicians were analyzed. The majority of the patients had no difficulty in the self-measurement of blood pressure and succeeded in reaching and maintaining the values of blood pressure within satisfactory levels, getting favourable psychological effects as well. Six patients (out of the ten who were indifferent or contrary to this practice) went on measuring the arteria pressure, giving in this way a contribution to a better management of the disease. The attitude of the attending physicians was on the whole indifferent or negative towards this experience.


Chromatographic separation of autofluorescent and quenching substances from the hydrocarbon in tissue.

In spite of the recent progress in fluorometry, the measurement of carcinogenic hydrocarbons in tissue has been carried out with insufficient accuracy because of the presence of substances in the tissue interfering with fluorometry. Such substances, autofluorescent and quenching substances, were removed from ethanol extracts of the tissue by Sephadex LH-20 column chromatography. By elution of the column with ethanol, the interfering substances appeared in fractions of the void volume for 3-methylcholanthrene chromatography. In addition, the excitation wavelength for autofluorescent substances was found to be far from that for 3-methylcholanthrene, for which the excitation was at 300 nm and the luminescence was measured at 400 nm. Chromatographic separation of 3-methylcholanthrene and its metabolites in the bile and veces obtained from rats was done and only one peak consisting of conjugated metabolites was found on the chromatogram of the bile, though three peaks consisting respectively of the parent hydrocarbon with some metabolites, nonconjugated metabolites, and conjugated metabolites were observed in the feces. Total amounts of 3-methylcholanthrene and its metabolites, though the majority of the fluorescent substances were the parent hydrocarbon, in the lung and other organs were measured at various intervals after an intrabronchial application of 1 or 5 mg of 3-methylcholanthrene in Freund's incomplete adjuvant to rats. Preservation of the hydrocarbons in the treated lung was confirmed and this was considered to take part in the enhanced occurrence of epidermoid tumors in the lung.


Origin of leukemic cells in mouse leukemia induced by N-butylnitrosourea.

Administration of N-butylnitrosourea (BNU) induces leukemia in thymectomized C57BL/6J and C3Hf/Bi mice with almost the same high frequency as in non-thymectomized mice. Thymectomized and BNU-treated (C3Hf/Bi times CBA/H-T6T6)F1 mice receiving neonatal thymus tissues from C3Hf donors developed leukemias with or without marked enlargement of the grafts. The origin of leukemic cells was analysed by T6 marker chromosome and thymus allo-antigen theta in this hybrid system. Cells from leukemia with enlarged thymus grafts possessed the sigma-antigen detected by cytotoxicity tests. Cells from leukemia without thymus involvement had no sigma antigen. The leukemic cells arising at the site of thymus grafts were derived from the graft itself (C3Hf) or from the host (C3Hf times CBA/H-T6T6)F1 cells, most probably bone marrow cells which are repopulating into the graft. When the mice were treated with BNU after the lymphoid elements in the grafted thymus had been replaced by host cells, leukemia mainly composed of host-origin cells developed. Leukemia in which neoplastic cells in the thymus grafts were of donor origin and those in other hematopoietic tissues were of host origin was found not infrequently. The present results mean that the target cells in BNU leukemogenesis are distributed within and outside the thymus and that some leukemias are of multifocal tissue origin.


Effect of injection of nuclear fraction from Rhodamine sarcoma on turnover of liver catalase.

1) When nuclear fraction prepared from Rhodamine sarcoma (sarcoma nuclear fraction) was injected into mice three times every 24 hr, the catalase activity of the liver decreased to one-third of the original activity. 2) By the injection of sarcoma nuclear fraction into mice, the catalase activity with the soluble fraction from homogenates of the liver decreased more significantly than that with the particulate fraction from them. 3) Immunological titration proved that the decrease of catalase activity in the liver of mice injected with sarcoma nuclear fraction was brought about by decrease in the amount of catalase protein. 4) In the mice, whose liver catalase activity had been irreversibly inhibited by injection of 3-amino-1,2,4-triazole, the initial rate for the restoration of the liver catalase activity was significantly showed by further injection of sarcoma nuclear fraction. 5) When the inhibitor of catalase biosynthesis, allylisopropylacetamide, was injected into mice, the activity level of the liver catalase decreased. The extent of decrease by the injection of the inhibitor was slightly lower than that by the injection with sarcoma nuclear fraction, which was almost the same as the extent of decrease by the injection of sarcoma nuclear fraction plus allylisopropylacetamide. 6) It is conceivable that the catalase biosynthesis in the liver was inhibited by the injection of sarcoma nuclear fraction in almost the same manner as by the injection of allylisopropylacetamide. However, it is not certain whether the degradation of liver catalase was slightly stimulated by the injection of sarcoma nuclear fraction.


A variant of hexokinase isoenzymes detected in ascites tumor cells.

In the hexokinase isoenzyme pattern on the cellulose acetate membrane electropherogram of the supernatant fraction of Ehrlich ascites tumor cells, a band was detected moving slower than of common Type I isoenzyme. This band was assumed to be due to the presence of a variant of the hexokinase isoenzymes in the cells, since such a band was not detected in the normal tissues, and a change in the intensity of the band in response to a sulfhydryl agent, etc., differed from that of the common Type I and II isoenzymes. The band was also found in AH-7974 and MH-134 ascites tumor cells, in spite of the difference in the species of the tumor-bearing animals and originating tissue.


Induction of hepatocellular mitosis with carbon tetrachloride in late-phase Ehrlich ascites tumour-bearing mice.

Hepatocellular mitoses are scanty or absent in livers of animals in the late stages of growth of Ehrlich ascites tumours. The challenge of CCl4-induced liver necrosis in such animals is, however, met by a massive hepatocellular mitotic response. Thus general debility of the animal, imposing a block on liver cell division cannot be an explantation for the cessation of tumour-associated liver cell mitosis in late-stage tumour-bearing animals. Possible explantations for the pattern of hepatocellular mitosis in relation to duration of tumour growth are discussed.


Effect of feeding and lighting on the regulation of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the liver, small intestine, and lung of mice.

The effect of feeding and lighting on the regulation of aryl hydrocarbon hydroxylase activity in liver, small intestine, and lung from C3H/He, DBA/2, and Swiss albino mice was investigated. A circadian rhythm of aryl hydrocarbon hydroxylase activity in the liver from DBA/2 mice was observed under the controlled lighting conditions, showing higher activity at the end of the light period of a day and lower activity in the dark period. Contrasting to the change of the enzyme activity in mice fed freely in the continuous dark period, inconsistent and variable results of the enzyme activity and its induction by 3-methylcholanthrene were observed in the mice that were fed during the continuous light period, depending on the sex and strain of the mice used. Different responses in the induction of aryl hydrocarbon hydroxylase to different routes of 3-methylcholanthrene administration were found between the liver and small intestine of the mice, but not in the lung. The higher levels of the enzyme activity induced in the liver and small intestine were detected after the intraperitoneal and intragastric administration of 3-methylcholanthrene. The significance of controlled feeding schedules for obtaining reproducible experimental results in the regulation of aryl hydrocarbon hydroxylase activity in the mice was discussed.


Cell kinetics of gastric carcinoma and other gastric lesions in rats by N-methyl-N'-nitro-N-nitrosoguanidine with or without Tween 60.

Male Wistar rats were divided into three groups for studying the chronic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), in continuous dose of 50 mg/L in drinking water, or 50 mg/L MNNG and 0.4% Tween 60 in drinking water. From the 2nd to 50th week after the administration of MNNG, every 3 or 5 rats were sacrificed and autopsied after the intraperitoneal injection of 1 muCi 3-H-thymidine/g body weight at 2- or 3-week intervals. The resected stomachs were studied morphologically and autoradiographically. Six cases of experimental gastric cancer were produced that fulfilled Stewart's criteria. Autoradiographically, there was no significant different in the flash labeling index in the normal antral mucosa, in the non-pathologic antral mucosa, and in the cancerous lesion, but generation time and DNA synthesizing time of the cancerous lesion were 2 or 3 times longer than those of the glandular stomach of normal rats reported by Galjaard. They were also longer than those of the non-pathologic antral mucosa of rats treated with MNNG. These experiments results were discussed, comparing with cell kinetics of the gastrointestinal tracts in man.


Effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl[-1(2-chloroethyl)-1-nitrosourea hydrochloride on lymphoid leukemia L-1210.

A water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), was tested for antitumor activity against lymphoid leukemia L-1210 in BDF1 mice. The results obtained were as follows: (1) ip--ip system: By daily administrations optimal dose for 12 days, MED (ILS40), and therapeutic ratio were found to be 18 mg/kg, 1.3 mg/kg, and 14, respectively, and by a single injection, those were found to be 46 mg/kg, 4.2 mg/kg, and 11, respectively. The therapeutic ratio of ACNU was the highest of all the drugs tested. At the neighboring dose level to optimal dose most of leukemic mice survived more than 60 days. (2) ip--iv system: Remarkable prolongation of life-span was observed by a single injection. Majority of mice administered more than 32 mg/kg of ACNU survived more than 60 days. (3) ip--po system: Remarkable prolongation of life-span was shown by a single administration and most of leukemic mice given more than 46 mg/kg of ACNU survived over 60 days. (4) iv--ip system: By a single administration of ACNU remarkable prolongation of life-span was seen and majority of leukemic mice were rescused at doses of 32 mg/kg or more. (5) iv--iv system: Result almost similar to iv--ip system was obtained. (6) iv--po system: The result in this system was similar to that in ip--po system.  Thus, the compound was highly effective in leukemic mice by either its parenteral or oral administration.


Change in immunosensitivity of Yoshida sarcoma produced by chemical modification of cell-surface membrane.

Change in immunosensitivity of various chemically modified cells to the specific antibody was investigated in the Donryu rat-Yoshida sarcoma system. Among various agents, Amphotericin-B and cetyltrimethylammonium bromide were effective in increasing the immunosensitivity. This effect was not due to the general damage of cell membrane but to the increase of antigen exposed on the cell-surface membrane.


Difference in sedimentation profiles on DNA from various cell types during lysis periods by direct alkaline sucrose gradient analysis.

Sedimentation condition for DNA from various kinds of cultured mammalian cells lysed directly on the top of an alkaline sucrose gradient was examined after the lysis for various periods at 19 degrees or 37 degrees. When cultured normal embryo cells from human, mouse, and Syrian hamster were analyzed, "complex" and "main" peaks were demonstrated. The former, which had low sedimentation coefficient, was obtained after 1 or 2 hr of lysis at 19 degrees and resolved after a 4-hr lysis into the latter which had a higher sedimentation coefficient. When cultured cells with malignant history were analyzed, a sharp and high peak was observed after 1 or 2 hr of lysis of 19 degrees and this peak resolved into the "main" peak after a 4-hr lysis. When the cells were lysed at 37 degrees, the "main" peak appeared after 1 or 2 hr of lysis. Metaphase cells in which the chromatin is condensed heterchromatically were also analyzed. Sedimentation profiles from normal human embryo cells and HeLa cells in metaphase were similar to those obtained from cells with malignant history in interphase during various lysis periods. From these data the difference in the sedimentation pattern between normal embryo cells and cells with malignant history could be interpreted as a phenotypic expression of the cells.


Induction of tumors of the nervous system in the ACI/N rat with 1-butyl-1-nitrosourea administered transplacentally, neonatally, or via maternal milk.

1-Butyl-1-nitrosourea (BNU), a strong leukemogen for rats and mice, was administered prenatally, neonatally, and to sucklings via maternal milk in the ACI/N rats. A high incidence of neurogeneous tumor was obtained in the offspring of the mother rats that received 3 subcutaneous injections of 10 mg/rat of BNU at the late stage of pregnancy and also in the animals that received one subcutaneous injection of 100 mg/kg of BNU within 24 hr after birth. Though in low incidence, the tumors also developed in the offspring of the mothers that received the BNU treatment at the middle stage of their pregnancy or in the rats that were nursed by the mother rats which received 3 subcutaneous injections of 300 mg/kg of BNU during lactation. Contrary to expectations, leukemia developed in only one rat of all the offspring of the mother animals that received the BNU treatment during their pregnancy.


Tea-gruel as a possible factor for cancer for the esophagus.

Specific death rates for esophageal cancer by each city and county in Japan were calculated. Nara and Wakayama Prefectures formed a high death-rate area with some neighboring cities and counties in other perfectures. Inhabitants of these area are known by the custom of taking "Chagayu", tea-cooked rice gruel. According to this survey on the habit of taking hot tea-gruel, with over 5,000 teachers and their families aged over 50 years old, the distribution of the precentages of taking tea-gruel among surveyed subjects by cities and counties was similar to that of the death rates for esophageal cancer. Also, in Yamaguchi Prefecture, western-most prefecture of the main island (Honshu), there was an area which showed a similar condition. The result of this survey suggests that taking hot tea-gruel is one of possible factors for esophageal cancer in these districts.


Abnormal regeneration of hydra induced with vinblastine sulfate.

The effect of vinblastine sulfate on the regeneration of hydra was examined. When the three segments of hydra (fore, mid, and hind segments) were treated with 0.01% vinblastine sulfate immediately after separation, transferred to normal culture medium, and observed for 7 days, various types of abnormal regeneration were observed, especially in the regenerates from the mid segments. Other segments of hydra did not reveal any abnormal pattern of regeneration, although incomplete regeneration or no regeneration of the segments was seen in the advanced period of the treatment. In the case of treatment of the three segments with 0.01% vincristine sulfate, no abnormal regeneration was seen, in spite of marked inhibition of regeneration which was observed in the advanced period of the treatment.


Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. II. Variations in surface architecture found by scanning electron microscopy.

We have used the high resolution and the great depth of focus possible with the scanning electron microscope to define the surface features of normal human colon and human colonic polyps. This technique demonstrates that the surface of the normal colon has a territorialization which encompasses multiple crypts. The surface of the normal colon is covered with both absorptive cells and goblet cells. Hyperplastic polyps are covered with overdeveloped absorptive cells and the normal teritorialization is present but is distorted. Adenomatous polyps are covered with immature cells and, except for the villous adenomas, goblet cells are strikingly absent from the surface. The territorial patterns are totally obliterated in the adenomas.


Similarity of arterial and intravenous vasopressin on portal and systemic hemodynamics.

The effects of superior mesenteric arterial and intravenous infusions of vasopressin and low and high dose intravenous infusions of vasopressin on splanchnic and systemic hemodynamics were compared in 20 anesthetized dogs. The following parameters were evaluated: flow in the superior mesenteric artery and portal vein, portal and systemic blood pressure, and cardiac output. In the comparison of selective arterial and intravenous infusions, no statistically significant difference was found between the degree of changes in portal flow, portal and systemic blood pressure, and cardiac output. Only the superior mesenteric artery flow showed a greater decrease with the selective arterial injection. In a comparison of intravenous high dose (corresponding to that used clinically) and low dose (one-fifth) infusions of vasopressin, a relatively high splanchnic and low systemic effectiveness of the low dose was found. It resulted in only a 15 to 20% smaller effect on flow in the superior mesenteric artery and portal vein and portal pressure; however, about 40% lesser systemic effect on arterial blood pressure and cardiac output than the high dose. The results of this experimental work warrant exploration in clinical practice, preferably by a controlled study. If clinical success in controlling hemorrhage confirms these hemodynamic results, an intravenous. low dose infusion of vasopressin would appear to be the method of choice in the vasoconstrictive therapy of gastrointestinal bleeding from varices.


Experimental esophagitis in cats impairs lower esophageal sphincter pressure.

We studied the effect of esophageal inflammation on lower esophageal sphincter (LES) pressure in cats by measuring LES pressure and taking mucosal biopsies before and after the development of experimental esophagitis, as well as after a 3 1/2-week recovery period. Perfusion of the esophagus with 0.1 N HCl for either 1 hr or 1/2 hr per day for 4 days produced inflammatory changes by mucosal biopsy and was associated with a marked decline in LES pressure. Upon resolution of the inflammation, LES pressure returned to normal. Biopsies were normal in control groups which underwent either esophageal perfusion with distilled water or intragastric perfusion with acid, 1 hr per day for 4 days, and LES pressures in these groups remained unchanged from pre-perfusion values. These studies indicate that lower esophageal inflammation per se adversely affects LES pressure in cats, and that experimental esophagitis may be a useful model for the study of LES function and its relation to esophageal inflammation.


Effect of nicotine on the lower esophageal sphincter. Studies on the mechanism of action.

Intravenous administration of nicotine sulfate caused a dose-dependent reduction in the lower exophagel sphincter pressure in anesthetized opossums. The maximal reduction in pressure of 85.0 +/- 2.6% was observed with a dose of 50 mug per kg. The effect of 50 mug per kg was not antagonized by bilateral cervical vagotomy, atropine, propranolol or by catecholamine depletion with reserpine. The sphincter relaxation produced by 50 mug per kg of nicotine was antagonized during tachyphylaxis produced by a larger dose (4 mg per kg) of nicotine. Nicotine tachyphylaxis also blocked the vagal-stimulated relaxation of the sphincter. It is suggested that the main action of nicotine on the sphincter in intact animals is caused by its effect on the noncholinergic, nonadrenergic inhibitory neurons which lie in the vagal pathway to the lower esophageal sphincter.


Effect of glucagon on esophageal motor function.

This study evaluates the effect of exogenous glucagon on esophageal motor function in man. Manometric studies were performed using an infused catheter system. Resting lower esophageal sphincter (LES) pressure was monitored before and after intravenous pulse doses of glucagon (1 to 100 mug). The effect of glucagon (0 mug ) on esophageal peristalsis was also studied. Multiple blood samples were taken for determination of glucagon, insulin, and glucose concentration. Glucagon effect on LES pressure was also evaluated after LES stimulation by continuous intravenous infusion and pentagastrin (0.04 mug per kg per min). Glucagon caused a transient significant decrease of LES pressure only at pulse doses (20 and 100 mug) which caused nonphysiological elevation of plasma glucagon levels. The temporal profile of decreased LES pressure correlated closely with maximal blood glucagon levels. Glucagon caused no demonstrable change in esophageal peristalsis. During LES stimulation by pentagastrin, glucagon caused significant transient decreases of LES pressure at doses as low as 1 mug per kg. We conclude that glucagon at sufficient dosage has an inhibitory effect on LES pressure. This inhibitory effect is not mediated through changes in serum insulin or glucose and appears to be pharmacological.


Plasma shedding by the canine oxyntic and pyloric glandular mucosa induced by topical action of acetylcholine. Effect of atropine and physostigmine.

Irrigation of the canine oxyntic or pyloric glandular mucosa in vagally denervated pouches with a solution of acetylcholine causes the mucosa to shed plasma proteins and the potential difference across the mucosa to fall. The response is dose-related with the threshold concentration of acetylcholine bromide ranging from 0.1 to 1 g per 100 ml. Topical application or intravenous injection of atropine prevents both plasma shedding and decline in potential difference. The minimal effective intravenous dose of atropine sulfate is about 0.007 mg per kg. The effect of irrigation with low concentrations of acetylcholine is enchanced by concurrent irrigation with physotigmine. The action of topical acetylcholine is not affected by concurrent irrigation with hexamethonium chloride (0.5 g per 100 ml) or by intravenous injection (5 mg per kg). Topical application of gallamine triethiodide (0.5 g per 100 ml) or d-tubocurarine (0.15 g per 100 ml) does not prevent the effects of acetylcholine in causing plasma shedding. Topical application of succinylcholine chloride (1 g per 100 ml) does not cause plasma shedding or a fall in potential difference.


Effect of atropine in reducing plasma protein shedding by the canine oxyntic glandular mucosa induced by topical irrigation with histamine or cobra venom.

The shedding of plasma protein by the canine oxyntic glandular mucosa induced by topical irrigation of the mucosa with a solution of histamine after the gastric mucosal barrier is broken is reduced by intravenous administration of atropine. Plasma shedding induced by repeated irrigation of the normal mucosa with solutions of Naja naja venom is likwise reduced by intravenous atropine. The nature of atropine-sensitive component of plasma shedding is unknown.


Calcium absorption by intestine. Stimulation in vitamin D-deficient nephrectomized rats by Solanum glaucophyllum.

The administration of an aqueous extract made from leaves of the South American plant Solanum glaucophyllum increased active duodenal calcium absorption 6-fold in sham operated vitamin D-deficient rats and 4.5-fold in comparable animals that had been nephrectomized. These results demonstrate that the active principle from the plant does not require renal metabolism for effects on intestinal calcium absorption, a biological activity previously observed only with sterols such as 1,25-dihydroxyvitamin D3 which have a 1-alpha hydroxyl group or a steric equivalent. The similarity of action between these lipid soluble sterols and the water soluble plant material may be explained by the presence of glycosidal alkaloidal steroids in plants from the genus Solanum.


True villous adenoma of the jejunum.

True villous adenoma of the jejunum is a rare lesion, first described by Keely and Gottlieb in 1969. Our case is similar in that it was benign and presented with intermittent intussusception. An important difference was the presence of multiple gastrointestinal neoplasia, thereby resembling villous adenomas of the colon. The pathological differentiation of true villous adenoma and adenomatous polyp is discussed.


Pigmented corneal rings in a patient with primary biliary cirrhosis.

A patient with primary biliary cirrhosis who had high hepatic, serum, and urine copper levels was found by slit-lamp biomicroscopy to have pigmented corneal rings similar to Kayser-Fleischer rings. Wilson's disease was excluded on the basis of the elevated serum ceruloplasmin and copper levels, the lack of neurological disease despite advanced liver disease, a negative family history, and the typical clinical features of primary biliary cirrhosis. Although the exact chemical nature of the corneal rings is unknown, the cornea may be another tissue associated with elevated tissue copper levels in primary biliary cirrhosis.


Hepatic portal vein gas without bowel infarction or necrosis.

Spontaneously developing intrahepatic portal vein gas is usually associated with necrotic bowel, bacteremia, or both. Very few patients with this radiographic sign survive. A postoperative patient with severe abdominal pain and distention was found to have hepatic portal vein gas. At exploration two intraperitoneal abscesses were found and drained. The bowel was unremarkable. The patient had an uncomplicated postoperative course. Abscesses have not been associated with the development of intrahepatic portal vein gas. It is rare for this "diagnostic sign" not to be associated with necrotic bowel and a very bad prognosis.


Isolated liver nodules.

Thirteen examples of isolated liver nodules were examined in 7 persons, 4 with single nodules and 3 with multiple nodules. Pathologically they present a spectrum from a solid structure that resembles liver parenchyma with varying degrees of disorganization and fibrosis to soft and fatty enough to superficially resemble a lipoma. Abnormal blood vessels were commonly found in and around the nodules, and the nodules were all ischemic compared to surrounding normal liver. The association of abnormal blood vessels and ischemia may be a cause and effect relationship. Studies by angiography might prove two things: (1) that the presence of abnormal blood vessels is constant in the lesions; (2) that the vessels, although relatively large, fail to provide adequate blood supply to the area, either by lack of branches or by some type of shunting mechanism. Review of cases of "lipoma of the liver" reported in the literature suggest that the lesions described are, in fact, the fatty type of isolated liver nodules.


Microfilament dysfunction as a possible cause of intrahepatic cholestasis.

The effects of cytochalasin B on bile canalicular structure and function were examined. Three experimental models were used, cultured hepatocytes, isolated perfused liver, and in vivo infused liver. The techniques used were light and electron microscopy and, in selected instances, scanning electron microscopy, electron "stains" for microfilaments, and measurements of bile flow. Microfilament disruption and dilation of bile canaliculi were consistently found and closely paralleled a reduction in bile flow in both in vitro and in vivo infused animals. It is proposed that under normal circumstances, the microfilaments maintain the canaliculi in a contracted or partly contracted state. Hence, the microfilamentous network would provide tone to the canalicular system which would tend to reduce stagnation and facilitate the flow of bile. Removal of normal microfilament contractile function would be expected to produce canalicular ectasia and reduction of bile flow, as was observed. Microfilament dysfunction may therefore be a possible cause of intrahepatic cholestasis. Crucial to this hypothesis are the presence of actin-containing microfilaments in the pericanalicular web, and an action of cytochalasin B on their contractility. Evidence pertaining to these requirements is presented and discused.


Metabolism of lethocholate in healthy man. I. Biotransformation and biliary excretion of intravenously administered lithocholate, lithocholylglycine, and their sulfates.

The metabolism of intravenously injected radiolabeled lithocholate, lithocholylglycine, and their 3alpha-sulfate esters was characterized in healthy subjects. Lithocholate radioactivity was excreted rapidly and predominantly in bile; the excreted radioactivity had the chromatographic properties of glycine and taurine conjugates of lithocholate, of which 60% were sulfated. Lithocholylglycine also was excreted rapidly and predominantly in bile, and 60% of excreted radioacitvity was sulfated. Sulfolithocholate radioactivity was only partially conjugated (about 60%) in association with biliary excretion. Sulfolithocholylglycine was excreted unchanged in bile. Neither sulfated derivative showed appreciable excretion in urine, although both were excreted more slowly in bile than unsulfated free or conjugated lithocholate. The data suggest that unconjugated lithocholate which is absorbed is completely conjugated and partially sulfated before excretion which occurs exclusively in bile. Since sulfation is not complete, some unsulfated lithocholate is always present in bile. This conjugated but unsulfated lithocholate, if reabsorbed, would be again partially sulfated during its next enterohepatic circulation. Thus, the end result of these biotransformations would be for absorbed lithocholate to be excreted in bile mostly, but not entirely as the sulfated conjugates.


Portal and systemic effects of selective infusion of vasopressin into the superior mesenteric artery in cirrhotic patients.

Selective infusion of vasopressin (0.2 U per min) was performed in 8 cirrhotic patients with portal hypertension who underwent umbilicoportal catheterization. There was a significantly decreased (9.6%) of the free portal venous pressure from 27.0 plus or minus 1.4 mm Hg to 24.4 plus or minus 1.4 mm Hg. In all patients, the portal PO2 significantly decreased with a mean fall of 18.8%. However, in all patients, significant systemic effects were noted: an increase in arterial blood pressure and a decrease in the arterial PO2. In 3 patients, a marked fall of the cardiac output (greater than 2.0 liters per min) was recorded during the selective infusion of vasopressin. It is concluded that if selective infusion of vasopressin into the superior mesenteric artery is efficacious in the control of bleeding varices, the therapeutic effect cannot be totally explained by the lowering of the portal venous pressure in cirrhotic patients with portal hypertension. The risk of vascular thrombosis, the decreased portal PO2, and the systemic effects have to be considered when this approach is used in cirrhotic patients with ruptured esophageal and/or gastric varices.


Metabolism of lithocholate in healthy man. III. Plasma disappearance of radioactivity after intravenous injection of labeled lithocholate and its derivatives.

The plasma disappearance of intravenously injected radiolabeled lithocholate, lithocholylglycine, and their respective 3alpha-sulfates was defined in healthy subjects. Binding of these bile acids to serum protein in vitro was measured by ultrafiltration. Lithocholate and lithocholylglycine rapidly disappeared from plasma (t1/2 less than 3 min), showing a behavior similar to that of the other major primary bile acids present in man. However, after 15 min, when 99% of the radioactivity had been cleared, the disappearance curve flattened, and chromatography suggested that the chemical form of circulating radioactivity had become sulfolithocholylglycine, the end product of hepatic metabolism of lithocholate in man. Injected sulfolithocholate and sulfolithocholylglycine were cleared about one-fourth as rapidly. Lithocholate and its derivatives were tightly bound to serum proteins (87 to 99%); for a given steroid moiety and mode of conjugation, binding was altered slightly by sulfation, but all sulfated derivatives were tightly bound (greater than 95%) to serum protein. The results indicate that lithocholate, which enters the plasma compartment, whether unconjugated, conjugated, or conjugated and sulfated, will be protein-bound but nonetheless will be rapidly cleared from plasma.


Serum group I pepsinogens by radioimmunoassay in control subjects and patients with peptic ulcer.

Serum group I pepsinogen (PG I) levels have been determined by radioimmunoassay in 924 subjects. The mean levels in 300 healthy control subjects and in 389 hospitalized controls were 110.6 and 100.0 ng per ml, respectively. The "normal" range is estimated to be between 50 and 175 ng per ml. The mean level of serum PG I in 7 patients with Zollinger-Ellison syndrome was 503.9 ng per ml; values ranged between 315 and 921 ng per ml. The 77 patients with duodenal ulcer had a mean serum PG I level of 221.3 ng per ml; 49 (63.6%) had values greater than 175 ng per ml. The distribution of serum PG I values was bimodal in the patients with duodenal ulcer whereas it was unimodal in both groups of control subjects. Mean serum PG I levels in 13 patients with both duodenal and gastric ulcer and in 18 patients with prepyloric ulcer were, respectively, 177.2 and 179.4 ng per ml. Approximately one-half of these patients had high values. The 28 patients with gastric ulcer had a mean serum PG I level of 116.6 ng per ml; 6 (21.4%) had high values. With the exception of 3 patients with gastric ulcer, none of the 136 patients with peptic ulcer had a low (less than 50 ng per ml) level of serum PG I. In 37 patients with chronic alcoholism the mean level of serum PG I was 73.4 ng per ml. The observed gradient in the mean level of serum PG I among the groups of patients studied is similar to that which has been reported for maximally stimulated gastric acid output. This finding suggests that the secretory potential of the fundic gland mucosa of the stomach may be reflected by the level of PG I in serum.


Isoniazid-associated hepatitis in 114 patients.

Analysis of the overt hepatic disease that developed in 114 patients while taking isoniazid for chemoprophylaxis of tuberculosis showed it to be mainly hepatocellular. The severity of the hepatic injury was manifested by the 13 fatalities (12.3%) and by the histological demonstration of submassive necrosis in 9 and massive necrosis in 4 patients. The 20 other patients from whom hepatic tissue was available for study included 16 with moderately severe acute hepatocellular injury (4 had a mixed hepatocellular-cholestatic pattern), and 4 with chronic hepatic diseases (1 had cirrhosis). Clinical manifestations of hepatic disease prior to the onset of jaundice included vague digestive complaints in 55% of the group and "viral' disease-like complaints in 35%, some with and some without gastrointestinal symptoms. Jaundice was the presenting complaint in 10% of patients. Fever and rash were reported in very few patients (less than 4%) and eosinophilia of modest degree was noted in approximately 10%. Hepatic injury was recognized during the 1st month of isoniazid administration in 15% and during the 2nd month in an additional 31%. In the remaining 54% of patients, the drug had been administered for periods of 2 to 11 months before hepatic injury was noted. Analyses of variables suggested that hepatic injury which presented after 2 months, especially with bilirubin levels that exceeded 20 mg per 100 ml, was more likely to have a fatal outcome than disease that presented during the first 2 months even with higher bilirubin levels. The case fatality rate was significantly higher in black females than in black males or in whites of either sex. The observations of the present study offer no support for the view that isoniazid-induced hepatic disease results from hypersensitivity to the drug. Other data that support the view that hepatotoxic metabolites of isoniazid may be responsible for the injury are considered.


Kinetics of cholesterol and bile acids in patients with cholesterol cholelithiasis.

The kinetics of cholesterol and bile acid was determined from a 10-week analysis of the biliary lipids after a single injection of labeled cholesterol in parallel with a conventional 1-week study of primary bile acid kinetics. Six healthy controls and 6 patients with cholesterol cholelithiasis were studied. Two of the 6 cholesterol cholelithiasis subjects had kinetic values that were very similar to the controls and the other 4 were significantly different. These 4 patients had significantly smaller primary bile acid pools and significantly lower fractional conversions of cholesterol to both primary bile acids, with concomitantly lower bile acid flux. No significant differences were obtained for the size of the rapidly miscible cholesterol pool, the fractional rate of loss and flux of biliary neutral sterol, and the fractional turnover of the primary bile acid pools. These kinetic data support the hypothesis that in some patients with cholesterol cholelithiasis there is defective conversion of cholesterol to bile acids.


Toxicity of chenodeoxycholic acid in the rhesus monkey.

Chenodeoxycholic acid is an important drug for the treatment of cholesterol cholelithiasis in man. Although no toxicity has been demostrated in man, liver lesions develop in rhesus monkeys treated with chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid was fed daily to three groups of 6 animals each at the following dose: 10, 40, and 100 mg per kg; 2 separate animals were not treated and served as controls. After 1 month, the animals were killed. During the treatment period, most blood tests (e.g., blood count, blood urea nitrogen, albumin, SGOT, lactate dehydrogenase) remained within normal limits, but there was a significant dose-related increase in serum leucine aminopeptidase levels. The percentage of lithochlic acid, the 7-dehydroxylated bacterial metabolite of chenodeoxycholic acid, rose from 1% in the control animal to almost 14% in the 100 mg per kg-treated group. Liver biopsies obtained before treatment and at necropsy showed no significant changes. Thus, exposure of the liver to increased amounts of lithocholic acid during chenodeoxycholic acid treatment might result in elevation of serum leucine aminopeptidase activity.


Effect of portacaval shunt and arterialization of the liver on bile acid metabolism.

The effect on bile acid clearance of portacaval end-to-side shunt, with and without arterialization of the hepatic portal venous bed, was studied in dogs. Portacaval shunt reduced liver blood flow by 75%, and peripheral serum bile acid concentration rose from 3 to 239 muM. Arterialization maintained total liver blood flow within physiological range and serum bile acid concentration was only 19 muM. Since hepatic bile acid extraction was similar in both groups, bile acid clearance was determined largely by total liver blood flow. The results of this study indicate that hepatic clearance of substances originating from portal blood is impaired in portacaval shunt and can be restored by increasing the arterial blood supply to the liver.


Crohn's disease in a defined population. An epidemiological study of incidence, prevalence, mortality, and secular trends in the city of Malmö, Sweden.

A prospective epidemiological study of Crohn's disease in Malmö, Sweden, was carried out during the years 1958 to 1973. The mean annual incidence rate for the disease was 4.8 per 10(5) inhabitants at risk. The recorded incidence increased from 3.5 per 10(5) inhabitants during the initial 8-year period, to 6.0 per 10(5) inhabitants during the last 8 years of the study. The maximum annual incidence rate, 8.3 per 10(5) inhabitants in 1971, is the highest hitherto on record. A prevalence rate of 75.2 per 10(5) inhabitants on December 31, 1973 was recorded. The death rate was low: 0.15 per 10(5) inhabitants per year. The alidity of the observed high incidence rates and the rising secular trends are discussed.


Comparative studies of the intestinal absorption of [3H]pteroylmonoglutamate and [3H]pteroylheptaglutamate in man.

Comparative efficiencies of absorption of crystalline folic acid polyglutamate and monoglutamyl folic acid were determined in 11 normal subjects by measurement of the excretion of radioisotope in the urine after oral administration of [3H]pteroylheptaglutamic acid ([3H]PteGlu7) synthesized in our laboratory and of [3H]pteroylglutamic acid ([3H]PGA). Following ingestion of 0.6 mumole of [3H]PteGlu7, urinary excretion of radioactivity over 48 hr averaged 56.1 +/- 11.2% of the total dose. By comparison the ingestion of 0.6 mumole of [3H]PGA resulted in an average urinary excretion of 70.8 +/- 13.0% for the same time period. Approximately 90% of the urinary radioactivity was excreted during the initial 24-hr collection period. The mean recovery of radioactivity in urine and stool was 94% and recovery exceeded 84% in all subjects. The principal radioactive compound in the urine chromatographed with standard pteroylmonoglutamates. By chromatography, urinary folates were monoglutamates whether [3H]PGA or [3H]PteGlu7 was administered. The time course of folate absorption for the study compounds was compared by measuring the rise in serum radioactivity after the oral folate dose. Peak values in serum folate radioactivity following [3H]PGA occurred at 1 hr, whereas the peak values after [3H]PteGlu7 more often occurred at 2 hr. Only monoglutamyl folate was detected in the serum. These studies demonstrate that in normal subjects physiological doses of crystalline monoglutamyl and crystalline heptaglutamyl folates are both absorbed with high degrees of efficiency.


Pancreatic secretion of total protein and of three hydrolases collected in healthy subjects via duodenoscopic cannulation. Effects of secretin, pancreozymin, and caerulein.

Pancreatic secretion of total protein and of three types of hydrolases (amylase, lipase, and thymotrypsinogen(s) was determined in human subjects free of gastrointestinal disease. Pure pancreatic juice was collected by canulation of Wirsung's duct under duodenoscopy. Rapid intravenous injection of pancreozymin (1 Crick-Harper-Raper U per kg) stimulated secretion of total protein and hydrolases within 1 min. This stimulation was of short duration and had a half-life of 70 to 100 sec. Rapid intravenous injection of caerulein (20) ng per kg) induced a similar response. Parallel variations in total protein, amylase, lipase, and chymotrypsinogen(s) were observed in the three experiments where complete enzyme analyses were performed.


Effect of dioctyl sodium sulfosuccinate on structure and function of rodent and human intestine.

We tested the hypothesis that dioctyl sodium sulfosuccinate (DSS), an anionic detergent often described as a stool softener, blocks water absorption in the small and large intestines. Net water transport was measured under steady state conditions in vivo during single pass infusions of intestinal segments; each segment served as its own control. DSS, in concentrations which may obtain when it is fed in segments of rat jejunum, ileum, or colon. In man, 0.5 mM DSS inhibited water absorption by 80%. In rats, the degree of inhibition was linearly related to log10 of the concentration of DSS (0.1 to 2.0 mM). Furthermore, DSS altered the histological appearance of the surface absorptive cells of the rat colon. Because of these properties, DSS could be regarded as a stimulant laxative.


Control of the interdigestive myoelectric activity in dogs by the vagus nerves and pentagastrin.

In healthy, consious, intact fasted dogs, infusion of pentagastrin interrupted the interdigestive myoelectric complex in the stomach and small bowel and replaced it with activity that closely resembled that seen after feeding. After bilateral transthoracic vagotomy, pentagastrin infusion still interrupted the complex but now, in addition, upon stopping the pentagastrin, a premature activity front (phase III) of the complex was also followed by a reduction in the temporal regularity of the cycles of the complex. Fewer cycles per 10 hr occurred in most dogs after vagotomy, and the complexes were not as regularly interrupted by feeding a small meal of 50 g of meat as they had been before vagotomy. The results indicate that both neural and humoral influences have a role in controlling the interdigestive motor complex of dogs.


Radioautographic and quantitative studies on parietal and peptic cell kinetics in the mouse. A selective effect of gastrin on parietal cell proliferation.

Gastrin was given to mice subcutaneously at 8-hr intervals for 20 days. Control animals received only saline injections. With use of [3H]thymidine and radioautography, a significant increase in the production of new parietal cells (P less than 0.01) was observed in the gastrin-treated group. Increases in fundic progenitor cell DNA synthesis and shortened maturation time of the latter were demonstrated. Both could explain the observed changes in parietal cell kinetics. The quantitative estimation of parietal cell population after the administration of gastrin showed an increase in average parietal cell count per unit (P less than 0.01) and in total parietal cell number (P less than 0.05). This was consistent with the observed acceleration in the rate of parietal cell production under influence of gastrin. In contrast, no radioautographic difference in the proliferative activity of the peptic cells was observed between the gastrin-treated and the control mice. Moreover, at the end of the experiment, no changes in average peptic cell count per unit area, or in total peptic cell number, occurred under the effect of gastrin. The observation that peptic cells are renewed in a different way, independently from fundic progenitor cells and from parietal cells, was consistent with their peculiar lack in proliferative response to the hormone.


Changes in canine gastric acid output and serum gastrin levels following massive small intestinal resection.

Vagally denervated (Heidenhain) pouch acid outputs and serum gastrin concentrations, basal and in response to feeding, were measured in dogs before and after massive intestinal resection. Both 24-hr and postprandial Heidenhain pouch acid outputs increased (P less than 0.01) after intestinal resection. Increases in serum gastrin concentrations following feeding were greater after massive resection of the small intestine. There was an excellent correlation (r= 0.967; P less than 0.005) between increases in serum gastrin concentrations and Heidenhain pouch acid outputs after intestinal resection. These studies support and are consistent with the hypothesis that the polypeptide hormone gastrin plays a role in the production of the gastric acid hypersecretion which, in both dogs and man, frequently results from massive resection of the small intestine.


In vivo effect of bile salts and cholestyramine on intestinal anaerobic bacteria.

In vitro studies have shown that some bile salts inhibit the growth of intestinal bacteria. We investigated the possibility that bile salts might have a similar action in vivo in the ileum by performing serial anaerobic cultures and bile salt analyses on postprandial ileal fluid obtained anaerobically via intestinal tube. Five subjects were studied under control conditions, and after a 1-week course of orally administered cojugated bile salts in a dose shown to increase the bile salt pool. Three of the subjects were also studied after a 1-week course of cholestyramine. The numebr of ileal anaerobic microorganisms decreased significantly after both bile salt and cholestyramine treatment. Ileal bile salt concentrations were generally high (mean 9.2 mM) and did not change significantly after either bile salt or cholestyramine treatment. The results of this study are unexplained. Although it is possible that bile salts play a role in the regulation of small intestinal anaerobic flora, the lack of a relationship between ileal bile salt concentration and population levels of anaerobic organisms is puzzling and raises further questions about such a role for bile salts.


Omental arteriovenous fistula following liver biopsy.

A case of iatrogenic omental arteriovenous fistula attributable to an earlier unsuccessful liver biopsy is presented. The complications of liver biopsy and the role of arteriography in the diagnosis and management of visceral arteriovenous fistulas are discussed.


Reversibility of extensive liver damage in galactosemia.

An infant with galactosemia is reported in whom extensive liver damage developed by 1 month of age. Liver biopsy obtained prior to treatment indicated extensive periportal and intralobular fibrosis, ductular cysplasia. "pseudoglandular" transformation, and distortion of periportal vasculature. Three months after institution of a galactose-free diet, clinical and biological evidence of liver disease disappeared, and follow-up biopsy at 5 months of age showed normal hepatic histology. These findings demonstrate that functional and histological abnormalities consistent with cirrhosis can be completely reversed by dietary management in galactosemia.


Selective immunoglobulin a deficiency, ulcerative colitis, and gluten-sensitive enteropathy--a unique association.

A patient with selective immunoglobulin A deficiency, severe ulcerative colitis, and malabsorption had a flat jejunal mucosa demonstrated by peroral biopsy. Treatment at different times with a gluten-free diet for the jejunal lesion and corticosteroids for the ulcerative colitis, led to improvement of the malabsorption. A repeat jejunal biopsy demonstrated histological improvement of the jejunal mucosa, even though the colitis remained active. The occurrence of immunoglobulin A deficiency in a patient with ulcerative colitis and gluten-sensitive enteropathy is uncommon.


Reye's syndrome (encephalopathy and fatty liver). Diagnosis and treatment.

Reye's syndrome is an acute encephalopathy and fatty liver which has mainly been recognized in children through the age of about 16 years. Since the patients are not jaundiced and the liver may be relatively small at the moment of admission, the diagnosis must be sought by a high index of suspicion and the routine use of liver function studies, especially the SGOT, in all unexplained cases of encephalopathy. Early treatment and appropriate management of cerebral edema seem to reduce the over-all mortality of Reye's syndrome from more than 50% to less than 20%. Alert gastroenterologists may find some adult cases of Reye's syndrome masquerading as acute neurological disease or supposed acute drug reactions.


[The present status of the treatment of male factors of infertility in barren couples with special reference to co-operation between andrologists and gynaecologists (author's transl)].

The interests of a barren couple are seen as the desire to obtain their own child with medical aid irrespective of the methodology of medical aid as long as there is success. At times quarrels over competency are an impediment to a coordinated treatment of the barren couple. At times treatment is thus precluded. A practical co-operation between andrologists and gynaecologists should be possible. It is important that the exchange of information is improved on the methods of investigation, on the interpretation of the tests results and on the plan of management for each partner of the infertile couple. Treatment of male infertility is not as hopeless as it is still portrayed. However one should not ask for the impossible of the treatment of male infertility since the most optimal seminal analysis result is useless in the presence of a monophysic menstrual cycle in the partner. The andrologist thrives for an improved differential diagnosis in order to select male patients who require treatment and in order to treat these more selectively. A single preparation for the treatment of all cases of male infertility does not exist just as much as a single preparation for the treatment of all menstrual anomalies in women does not exist.


[Trace elements in the human placenta (author's transl)].

The determination of the mentioned elements was carried out by the neutron activation analysis with lollowing radio-chemical separation. The comparison of trace elements in the human placenta from different regions of Bavaria showed a high concentration of Sb, Br, La and Co in Munich. This fact is explained by the environmental pollution of the large city. Placentas from the Bavarian forest contained a higher amount of Ce and Hg. Cer is contained in the rock of this region. The increase in Hg from that region is unexplained.


[Statistics--a panacea? (author's transl)].

The fundamentals of statistics and the limitations of statistics are discussed from their practical and philosophical aspects. In summary results based on statistical methods should be reviewed again and again and corrected if necessary and one should not disregard results which have already been obtained by other basic sciences. In a given goal and the related expectations and opinions it is erroneous to rely completely on the results of a statistical and mathematical calculation. A definitive border between secure knowledge and mere opinion cannot be obtained. Only degrees of certainty exist. The problems of the calculation methods for the perinatal mortality of newborns and their practical conclusions and the question of the relationship between income and number of offspring are used to show that statistical and mathematical methods have their value but cannot be a goal in themselves. It is dangerous to persist in the uncritical belief that each number is equivalent to absolute truth as long as it recorded accurately enough. The ancillary science of statistics does not furnish a general comprehension of the subject matter in natural sciences and the humanities.


[Estradiol-17beta, estrone, LH and FSH in serum after administration of estradiol-17beta, estradiolbenzoate, estradiol-valeriate and estradiol-undecylate in the female (author's transl)].

Estradiol-17beta, estradiol-benzoate, estradiol-valerianate, and estradiol-undecylate were injected intravenously and intramuscularly to postmenopausal woman and to female castrates. Equal doses were used corresponding to 20 mg of free estradiol-17beta. Estradiol-17beta, estrone, FSH and LH were measured in serum by radioimmunoassay before and after application of the hormone and the estradiol esters. Thus the depot effect of the different esters could be compared.


[The effect of Bactrim and Tandearil on abnormal tubal patency in cases of infertility (author's transl)].

In 257 patients with primary or secondary infertility, tubal occlusion or impeded tubal patency was found. The patients received Bactrim or Tandearil and the tubal patency was retested. In a control group of 74 cases, 2 tubal patency tests were done without treatment. Following treatment with Bactrim, 40,4% of the previously occluded fallopian tubes were patent. Following treatment with Tandearil, 34% of the previously occluded tubes were patient. In the non-treated group, 25% of the cases showed tubal patency at the second patency test. The results were more striking for the cases with impeded tubal patency. The success rate was 73,3% following treatment with Bactrim, 50% following treatment with Tandearil and 26,7% in the untreated control group.


The mating system and microevolution.

Studies of natural and experimental plant populations have revealed that genotypic frequency distributions are highly structured in predominantly selfing species. This high degree of genetic organization is manifested in intense correlations in allelic state over loci and also in striking micro-geographical heterogeneity. Both aspects of this structure are facilitated by self-fertilization. Development of non-random associations of alleles within populations is facilitated because inbreeding reduces heterozygosity and thus also the randomizing effect of recombination. Spatial differentiation is facilitated because self-fertilization retards gene flow from population to population. The effect of organizing the entire populational genotype into a sort of giant supergene is to increase the frequency in the population of genotypes which confers high fitness and hence to increase adaptation to the local environment. However the recombinational potential remains substantial. As a result considerable free genetic variability remains in the population and it is available for long-term response to natural selection. Thus the organization of genetic variability within populations provides for high immediate fitness and also for flexibility to meet longer term evolutionary needs. At the same time selfing is a barrier to migration and it promotes the development and maintenance of different multilocus organizations in adjacent populations occupying unlike habitats. In total, therfore, a pattern of genetic differentiation develops in space which is an almost exact overlay of the environmental heterogeneity. The plant genetic and plant breeding literature contains extensive evidence that the mating system in plants can be modified simply and drastically by selection and that different populations within the same species often practice very different amounts of inbreeding. Considering the ease with which the mating system can be altered, and the benefits of adjusting genetic variability through regulation of the mating system, it is not surprising that a high proportion of flowering plants self-fertilize to some extent and that at least one-third of species have adopted predominant selfing as a strategy in ecogenetic adaptation.


Evolution of HL-A and other major histocompatibility systems.

The HL-A region is a complex highly polymorphic system containing many genes with interrelated functions on the cell surface. Population data suggest the action of natural selection, perhaps via linked immune-response genes. Major histocompatibility systems, such as HL-A,  are presumed to have their counterparts in at least all mammalian species. The complexity of the  region suggests evolution by gene duplication. The integrity of the region may even extend to the human equivalent of the complex T locus of the mouse.


Mutagenesis of haploid cultured frog cells.

Haploid cells afford an opportunity to test some of the assumptions from bacterial genetics which have been adopted by somatic cell geneticists. Haploid cultured cell lines derived from the grass frog Rana pipiens were compared to diploid cell lines in order to test a model which predicts that recessive mutations will be expressed in diploid cells with a frequency equal to the square of that in haploid cells. Haploid and diploid monolayer cultures were compared for (1) survival after exposure to compounds known to be mutagenic for bacteria (a measure of the frequency with which lethal mutations are expressed), and (2) the induction of drug-resistant variants (putative mutants) by such compounds. The proportion of cells which survived from diploid cultures was no more than ten times that from haploid cultures, a much smaller difference than predicted. Furthermore, the frequency of drug-resistant variants was independent of polidy. Therefore, the validity of the following assumptions is in question: (1) Haploid eukaryotic cells express mutations with a frequency comparable to that in bacteria; (2) molecules which increase the frequency of stable phenotypic variants in culture do so by inducing gene mutations; (3) stable phenotypic variants whose frequency in culture is increased by putative mutagens arise as the result of gene mutation.


Genetic dissection of the excitable membrane of Paramecium.

Paramecium aurelia is chosen as the material for a genetic dissection of the excitable membrane. The simple innate behavior makes the behavioral analyses easy and mutant screening possible. Autogamy, which leads to complete homozygosity, guarantees the expression of recessive mutations. The size of these giant cells allows intracellular recording in electrophysiological studies.--Some two hundred lines of behavioral mutants are isolated. Several of them are studied in detail genetically, behaviorally as well as electrophysiologically. Mutants devoid of proper active electrogenesis are now available. Some of them are shown to be temperature-dependent. They have a slightly aberrant electric pattern when grown at the permissive temperatures and lose their excitability completely when cultured at the restrictive temperatures.--Systematic modifications of the membrane excitation process is demonstrated in this interdisciplinary study. Three unlinked mutations are shown to block the generation of Na-triggered depolarizations at different positions resulting in three different altered forms of electrical activities. The bioelectric profiles of 25 types of single or double mutants are now known. The search for the relevant gene products on the surface membrane is now underway.


Expression of phenotypes in hybrid somatic cells derived from the nervous system.

The techniques of somatic cell hybridization allow a genetic analysis of differentiated functions of mammalian cells in vitro. Clonal lines of mouse neuroblastoma cells expressing a variety of differentiated neuroectodermal functions have been fused to L cells not expressing these functions. The resulting NL hybirds, on a clonal basis, express a variety of parental and non-parental phenotypes. Some hybrid clones inherit the ability to synthesize the neurotransmitter acetylcholine (Ach) (expression of high levels of choline acetyltransferase, CAT) while others do not. The ability to synthesize Ach and the ability to degrade this neurotransmitter (high levels of acetylcholinesterase activity, AChE) appear to segregate independently in NL hybrid progeny.--When a a variety of clonal cell lines replicating in culture are fused to cells freshly derived from the embryonic nervous system, interesting phenotypes result in the hybrid progeny. Neuroblastoma x rodent nervous tissue hybrids express AChE and in a few instances have developed the ability to synthesize CAT. Transformed human fibroblasts fused to normal rodent nervous tissue yield hybrid progeny that retain human and segregate mouse chromosomes and isozymes. No expression of differentiated functions has yet been found in these latter hybrids but they are useful for mapping mouse genes.


Effect of age on liver function.

Serum concentrations of bilirubin, alkaline phosphatase, and GOT as well as the retention of BSP and 131I-rose bengal were determined in 43 normal subjects over 50 years old for the purpose of evaluating age-dependent variations. The normalcy of the liver in all subjects was confirmed by biopsy. The values of serum bilirubin, alkaline phosphatase, and GOT were unaltered with increasing age. Age also had no effect on the retention of BSP and 131I-rose bengal, in contrast to some previous studies in which the normalcy of the liver was not satisfactorily established. No variations between the sexes were seen in our study. The median of the 45 minute BSP retention test was 4.2 percent, with a ninth decile of 7.5 percent. The median of the retention of 131I-rose bengal was 32 percent, with a ninth decile of 39.4 percent.


Hepatitis-associated-antigen-positive hepatitis in a tuberculosis unit.

An outbreak of hepatitis-associated-antigen-(HB Ag)-positive hepatitis in a hospital unit for the care of male patients with pulmonary tuberculosis is described. Sixty-four patients were studied of whom 37 were HB Ag positive. Hepatitis developed in at least 20 and was icteric in 11. The illness was mild, without fatality due to hepatitis and persistent jaundice did not occur. A carrier state developed in 15 of 24 HB Ag-positive patients followed up for more than six months and was unrelated to the presence or absence of initial hepatitis. Spread of HB Ag to domestic and medical staff occurred and following the discharge of the patients, household contacts became positive. Five, all wives of patients, developed jaundice. Faeces and sputum were HB Ag negative in seropositive cases. The origin of the outbreak remains undetected. The probability of non-parenteral transmission of HB Ag in this outbreak is discussed. Closure of the unit, isolation of HB Ag-positive cases with separate toilet and kitchen facilities, and discharge of patients when their respiratory condition allowed, resulted in prevention of further spread and eventually all patients were discharged from the unit.


Endotoxin-induced liver necrosis and intravascular coagulation in rats enhanced by portacaval collateral circulation.

The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.


The intrinsic innervation of the human alimentary tract and its relation to function.

The intrinsic innervation of the human gut has been studied in strips of circular and longitudinal muscle removed at operation. Electrical stimulation of the nerves at a wide range of frequencies (0-1 to 128 Hz) can evoke a variety of responses due to activation of four types of nerves. There is evidence for cholinergic, adrenergic, non-adrenergic inhibitory, and non-cholinergic excitatory fibres, which may be stimulated at different frequencies. The various regions of the alimentary tract, and even the muscle layers within a region, may respond differently to nerve stimulation. This is most marked at 4 Hz and the observed differences correlate with the function of each part and its dependence on extrinsic innervation. The stomach is relatively insensitive to electrical stimulation, and this is consistent with its reliance on vagal innervation. The dominant excitatory responses in the longitudinal muscle of the oesophagus and ileum correlate with their high motility and propulsive function, whereas the dominant inhibitory responses in the colon correlate with its lower motility and storage function.


Assessment of simple methods of measuring intestinal transit times in children with gastroenteritis.

Intestinal transit times in children less than 3 years old with gastroenteritis were measured using carmine suspension and radioopaque pellets. Carmine transit times were short as expected in the acute illness, and lengthened on recovery to the values found in children without diarrhoea. Pellet transit times of the sick children were the same as those of controls without bowel disease. Solid markers may thus be misleading in acute diarrhoeal illness of childhood. Possible mechanisms are discussed.


The nutritive effect of glucose on the structure and function of jejunal self-emptying blind loops in the rat.

In an attempt to obtain further information on the influence of the intestinal contents on the development of mucosal structure and function, self-emptying blind loops of rat jejunum were constructed, and the oral end was exteriorized with a stoma to permit infusion of different solutions into the loop. Ringer solution or media containing glucose or galactose was instilled into the loops three times daily for 27 days before functional and structural examination of the loops. The body weight and food intake of the animals did not differ significantly from one group to another. Treatment with glucose, but not with galactose or Ringer solution alone, induced a significant increase in the villus height. Disaccharidase but not dipeptidase activity was concomitantly increased. Infusion of glucose or galactose both led to an increase in the transport capacity of the loop, as determined by glucose absorption in vivo. These results indicate that glucose has a nutritive effect, probably due to its intracellular metabolism, which is responsible for the structural alterations observed. On the other hand, the increase in transport capacity  may be attributed to substrate-induced stimulation of the specific monosaccharide transport system in the epithelial cell.


The influence of food intake on the development of structural and functional adaptation following ileal resection in the rat.

The present study was undertaken to determine the influence of hyperphagia on the adaptive changes occurring in the rat jejunal mucosa as a result of intestinal resection. One group of resected rats was subjected to pair feeding with a sham-operated population, whilst another group was nourished ad libitum. The animals which ate ad libitum developed hypertrophy of the mucosa which was accompanied by increased glucose absorption in vivo without changes in enzyme levels. These alterations were much less pronounced in the pair-fed group of resected animals, a finding that indicates that the adaptive changes are at least partially influenced by increased luminal nutrition.


Effect of bile acids on electrical properties of rat colon: evaluation of an in-vitro model for secretion.

A preparation of rat colon mucosa has been evaluated as a useful model to study effects of bile acids on the changes in short-circuit current and transmural electrical potential difference (pd) which others have associated with alterations in electrolyte transport. Using this preparation, it was found that bile acids were effective in increasing short-circuit current and pd when applied to the serosal, but not the mucosal, surface of the tissue. Furthermore, taurine-conjugated cholic acid, which has no demonstrable effect on the colon in vivo, was found to increase short-circuit current and pd significantly in the in-vitro preparation. These data indicate the limitations of the in-vitro model in studying the mechanism of bile acid-stimulated intestinal secretion.


Influence of pudendal block on the function of the anal sphincters.

The function of the anal sphincters has been studied by obtaining continuous recordings of the pressure in the anal canal and the electromyographic activity in the striated sphincter muscles during expansion of the ampulla recti by means of an air balloon. Ten healthy subjects were examined before and after the striated muscles had been entirely paralysed by bilateral pudendal block, making it possible to record the activity from the internal sphincter alone. The results show that the internal sphincter contributes about 85% of the pressure in the anal canal at rest but only about 40% after a sudden substantial distension of the rectum. During constant substantial rectal distension, the internal sphincter accounts for about 65% of the anal pressure. It is concluded that the internal sphincter in the adult is chiefly responsible for anal continence at rest. In the event of sudden substantial distension of the rectum, continence is maintained by the striated sphincter muscles, whereas both sphincter systems probably have an important function during constant distension of the rectum.


Growth hormone secretion in the rat as a function of age.

The first appearance of rat growth hormone (RGH) in serum was in the 19 day-old foetus. The level was high on the 21st day of gestation (129 +/- 7 ng/ml serum), it decreased after birth and descended to 17 +/- 2 ng/ml in the 15 day-old rat. After weanling it again rose to reach a plateau at 80 cays. The half-life and metabolic clearance rate (MCR) of RGH were compared in the 4 and 15 day-old rat and in normal and hypophysectomized adult rats after a single intravenous injection of hormone. As the MCR was essentially the same in all groups, serum RGH levels reflect the rate of hormonal secretion of the pituitary gland.


Effect of cyproheptadine administration on insulin secretion in acromegalic, diabetic and normal subjects.

The effect of cyproheptadine (Cypro) and Placebo administration on insulin secretion and glucose utilization following i.v. glucose (IVGTT) was evaluated in 8 normal, 7 diabetic and 8 acromegalic subjects. Five of the diabetic subjects had overt diabetes and two of the diabetic subjects had "chemical" diabetes (oral GTT). One of the acromegalic subjects had overt diabetes, while one had borderline glucose tolerance and six had normal glucose tolerance (oral GTT). Cypro increased insulin secretion in the acromegalic but not in the diabetic or normal subjects. Methysergide (Methyl) increased insulin secretion in acromegalic and diabetic subjects but not in normal subjects. Methy and Cypro both increased insulin secretion in the same acromegalic subjects. None of the three groups of subjects had a modification in insulin secretion following Placebo administration. Neither Placebo, Cypro or Methy altered the glucose utilization rate contant (KG). There was no change in insulin half life or tissue sensitivity to insulin from Cypro (normal and acromegalic subjects) or Methy (normal subjects) administration. Despite their increase in insulin secretion in response to serotonin antagonists, acromegalic subjects have normal urinary 5-hydroxyindoleacetic acid excretion and normal serum serotonin concentrations. Their response cannot therefore be attributed to a generalized overproduction of serotonin.


Failure of parathormone to affect insulin and glucagon release from the perfused rat pancreas.

Parathormone (0.15 U/ml) failed to affect the rate of glucagon and insulin release by the perfused rat pancreas exposed to glucose in either low (3.3 mM) or high (8.3 mM) concentration. Parathormone also failed to interfere with the suppressive effect of glucose (16.6mM) upon glucagon release and its stimulatory action upon insulin secretion. Likewise, the biphasic release of both glucagon and insulin evoked by arginine (10.0 mM) in the presence of glucose (8.3 mM) was unaffected by parathormone. These findings suggest that the endocrine pancreas may not be a target organ for any direct and immediate action of parathormone.


The contribution of the pancreas and the intestine to the regulation of lipolysis in birds. I. Existence of highly potent lipolytic factors in ileum extracts.

Duck intestinal extracts were separated into three main peaks of proteins by chromatography on P6 BioGel columns. The first, which crossreacted with glucagon antibodies, gut "GLI", did not stimulate lipolysis in isolated chicken adipocytes. Both second and third peaks, corresponding to smaller molecular-size peptides were even more lipolytic than pancreatic glucagon.


Effect of quinestrol on plasma and urinary gonadotropins of postmenopausal women.

Ten postmenopausal women were given a 4-mg load of quinestrol by mouth and plasma FSH and LH were serially determined at monthly intervals. By bioassay, total urinary gonadotropins were also measured at the same times. Plasma FSH and apparent total gonadotropin levels in the urine were depressed to very low levels up to 3 months, while plasma LH was slightly affected. Tentative explanations of this discrepancy are presented.


The relation of hepatic in vitro inactivation of corticosteroids to the circadian rhythm of plasma corticosterone.

Plasma corticosterone levels and the in vitro capacity of the liver to reduce the delta(4)3-ketone group of corticosterone were ascertained at 4 hr intervals in male rats maintained on a normal lighting schedule (12L:12D). The rates of delta(4)3-ketone reduction, as well as wet liver weight, were highest during the early portion (08.00 hr) of the light period when liver protein and plasma corticosterone concentrations were low. Shortly (2000 hr) after the beginning of the dark period plasma corticosterone reached peak levels, while hepatic inactivation of corticosterone was markedly depressed. This inverse relationship suggests that the rhythmicity in the capacity of the liver to inactivate corticosterone may contribute to the circadian periodicity of plasma corticosterone.


The effect of diabetes on renal lysine utilization.

Current evidence indicates that a hydroxylysine-rich glycoprotein may be of importance in the structural organization and accumulation of glomerular basement membrane in the diabetic state. To further evaluate the role of insulin deficiency in renal glycoprotein synthesis, the effect of experimental diabetes on the incorporation and hydroxylation of 14C-lysine by cell-free systems prepared from rat renal cortex was examined. Microsomal protein synthesis was increased in diabetic preparations, but the rise in renal cortical collagen synthesis relative to total protein synthesis was greater. These changes were not duplicated by the addition of a mixture of unlabeled amino acids or hydroxylation cofactors to incubations with preparations from normal animals.


Purification and characterization of 2-alkenal reductase.

The purification of a 2-alkenal reductase to homogeneity from a rat liver 100 000 times g supernatant is described. Its molecular weight has been determined by Sephadex G-100 chromatography and sodium dodecylsulfate polyacrylamide gel electrophoresis before and after reduction with mercaptoethanol and carboxymethylation. The monometric form has a molecular weight of 45 000. It tends to form, to a very small extent, dimeric and trimeric aggregates of molecular weights 90 000 and 135 000. The isoelectric point (IP) was determined to be 6.2 by isoelectric focusing.


Ageing in vivo and neuraminidase treatment of rabbit erythrocytes: influence on half-life as assessed by 51Cr labelling.

Old and young rabbit erythrocytes, separated by centrifugation, contained different respective activities of glucose-6-phosphate dehydrogenase, pyruvate kinase and acetylcholinesterase, and different quantities of stromal sialic acid. A systematic study of the survival rate of young and old erythrocytes incubated with different amounts of Vibrio cholerae neuraminidase is described. The half-life of intact old erythrocytes is significantly shorter than that of young erythrocytes with a similar sialic acid content.


Simultaneous assay of neutral sugars and amino sugars by an automatic sugar analyzer: applications to glycoproteins.

The simultaneous assay of neutral sugars and amino sugars commonly found in glycoproteins is described. The automatic sugar analyzer used for the determination is based on the ion-exchange chromatography of sugar-borate complexes on a strong anion-exchange resin. The sugars are identified with the orcinol/sulfuric acid reagent. While less than 40 nmol of mannose, fucose, galactose, glucose, xylose, or arabinose is sufficient for analysis at least 200 nmol mannosamine, glucosamine, or galactosamine is required; acidic monosaccharides cannot be determined. The technique of sugar analysis is applied to structural studies on natural compounds, e.g. the monosaccharide composition of lichenan and the carbohydrate moiety of the glycoproteins ovomucoid and Collocalia mucoid.


Incorporation of orotic acid into nucleotides and RNA in mouse organs during 60 minutes.

Mouse kidney and liver were found to increase their levels of radioactivity above that of serum from 2 to 60 min after administration of [6-14C]orotic acid. In spleen, thymus and brain, the radioactivity level reached a maximum soon after the injection and then decreased, as did that in serum. Sixty minutes after the injection, 44% of the administered isotope dose was found in the kidneys, 22% in the liver and 0.75% in the spleen. The 14C activity in liver UTP increased rapidly and then remained constant for 60 min. The ratio between the activities in uridine phosphates and UDP-sugars was 3:4 from 10- 60 min after injection. In the liver and kidneys, the RNA 14C activities at 60 min after injection were 15% of the activity in their acid-soluble fractions. Intraperitoneal administration was found to be preferable to intravenous administration for studies on nucleotides and RNA in mouse liver, due to the delayed incorporation of the [14C]orotic acid activity into the nucleotide pool.


Rights of the mentally ill: the gulf between theory and reality.

Within the last few years several lawsuits have significantly increased both the procedural and the substantive rights of mental patients; among them are Lessard v. Schmidt, in which the court held that persons facing involuntary civil commitment are entiltled to dueprocess safeguards, and Wyatt v. Stickney and Donaldson v. O'Connor, concerned with the right ot adequate treatment. The author draws on the problems of implementing the landmark decree of Miranda v. Arizona, guaranteeing the rights of criminal suspects, in discussing the difficulties of translating rights promulgated in the courts into reality. He believes that enofrcement of patients' rights depends not on the law alone but also on the sensitivity and good faith of mental health workers.


Applying utilization review procedures in a community mental health center.

A large, multiservice community mental health center operates a utilization review program based on a three-level system of chart review by medical records personnel, a utilization review technician, and a committee of clinicians. Review is facilitated by a checklist for use in rating such issues as comprehensiveness, coordination, and quality of care aginst standards of care developed by the director of each service. The incompleteness of charts pulled for review is a continuing problem. But the system makes for efficient review and has various secondary benefits, such as the improvement of medical records. A survey made in the first year showed that staff had mixed feelings about the need for review, but that 60 per cent thought it was helpful all or most of the time.


The reporting habits of staff in a psychiatric hospital.

This study examined the frequency, length, and content of staff's discussions and written reports about 90 hospitalized psychiatric patients. The reporting habits of staff on three different units of one hospital were compared. On the units where nursing staff were primary case managers, discussion was less likely to include mention of treatment goals or plans than where psychiatrists were case managers, or where nursing staff were case managers and patients were encouraged to attend case reviews. There was no difference between the units on recording habits, but nursing staff were consistently more dependable than psychiatrist at record-keeping.


A goal list and a treatment methods index in an automated record system.

In conjunction with the development of a computerized goal-oriented record system at Forest Hospital Des Plaines, Illinois, research staff developed a psychiatric goal list from goal statements most frequently used at the hospital. Treatment methods written by hospital staff were also reviewed and classified under the goal statement for which they were most frequently written. The result is the Treatment Methods Index, which currently contains more than 500 goal statements and 1500 treatment method statements, and also lists all drugs and activity therapies used in the hospital. The index is stored in a computer, and a comprehensive treatment plan can be generated by entering the numbers of selected goals and treatment methods. The authors emphasize the advantages of the system in writing and updating treatment plans and its importance in peer review and other medical-care evaluations.


A behavior analysis report for assessing clients' needs.

The entry and assessment service of Harborview Community Mental Health Center, attepting to find the most suitable approach to diagnosis and assessment for its facility, developed the Behavior Analysis Report (BAR). The BAR is a five-part report written through the collaboration of both interviewer and client. It contains problem behaviors, adaptive behaviors and resources, treatment goals, disposition, and suggestions for treatment. The authors give sample descriptions from each part, together with a complete BAR.


Producing Marat/Sade: theater in a psychiatric hospital.

When a drama group in a small private psychiatric hospital decided to present Marat/Sade, a play about inmates in an insane asylum, some patients and many staff members reacted negatively. However, the drama group carried out its usual rehearsal activities, including improvisations, theater games, and exercises to work out characters' backgrounds, motivations, and feelings. The set and costumes were designed through elaborate improvisations during rehearsals. The group had to overcome various problems in producing the play, but they were no worse than those encountered in previous productions. The director believes that a hospital theater must have the same high standards as a good theater in any setting and that patients' drama groups can handle any aspect of theater.


Increasing hospital-community contact through a theater program in a psychiatric hospital.

In 1973 the activities therapy department at the Yale Psychiatric Institute began to organize and present plays before public audiences to help increase contact between patients and community members. Both patients and staff were anxious about opening the performances to the public; however, the first two plays were quite successful, and no serious disruptions occurred. When a third play was in rehearsal, the cast decided that it should be performed outside the hospital. the primary purpose of rehearsals, as well as separate weekly meetings with the director, was to provide a group identity that help the cast deal with their fears and anxieties. The outside performance, at a state hospital a hundred miles away, was well received and gave the cast a sense of achievement and increased self-esteem.


Integrating dance therapy into treatment.

For several years after dance therapy was introduced at Yale Psychiatric Institute in 1967, patients perceived it as an activity totally separate from their treatment program. The author describes changes in hospital procedure and in the structure of the dance groups that helped alter that perception. They include involving the patient's treatment team in the selection of activities; establishing groups in which membership is fairly constant, thus increasing the likelihood of interpersonal interaction; and setting aside ten or 15 minutes at the end of each dance session for discussion of the feelings evoked. The author says the changes have clarified values and goals within the dance therapy groups.


A survey of treatment modalities used by mental health clinicians and activity therapists.

An art therapist conducted a survey of 150 mental health clinicians and activity therapists to find which of ten treatment modalities they preferred to use with ten types of psychiatric patients. The final sample consisted of 68 respondents: 34 clinicians, 17 activity therapists, and 17 art therapists. The three respondent groups agreed on the same optimum treatment modality for five patient groups. Art therapists felt art therapy was most effective in treating the youthful drug abuser, the child with educational problems, and the moderately depressed patient. Clinicians and activity therapists agreed on other treatment modalities for those patients.


A multifaceted approach to psychodrama in a day treatment center.

Staff at the day treatment center at Norristown (Pa.) State Hospital have found several ways of using psychodrama to facilitate information gathering, diagnostic decision-making, and treatment planning and implementation. They use behavioral techniques such as role rehearsal and modeling. In addition they use techniques such as the mirror image, in vivo dramas, and slight deception to facilitate catharsis. These approaches, which broaden the applicability of psychodrama, are illustrated by case examples.