Immunologic alterations in patients with prostatic carcinoma.

The state of cell-mediated immunity was evaluated in 41 patients with prostatic carcinoma by determining their ability to demonstrate delayed cutaneous hypersensitivity with dinitrochlorobenzene and recall antigens, and to mount an inflammatory response to croton oil, as well as by measuring changes in monocyte chemotactic response. The patients were divided into 2 groups: those with localized disease and those with metastatic carcinoma. Monocyte chemotactic response provides an in vitro quantitative measure of effector cell function and was significantly depressed in the entire group of prostatic cancer patients as compared to non-cancer controls (p less than 0.05). Patients with metastatic carcinoma had a greater defect than those with localized disease (p less than 0.025). After radical prostatectomy a group of patients with localized disease tended to show improvement in monocyte chemotactic response (p less than 0.025). The ability of patients to develop a delayed cutaneous hypersensitivity response was impaired and correlated with the clinical stage of the disease. By using the cutaneous irritant, croton oil, the ability of these cancer patients to mount an inflammatory response was also found to be impaired and showed a close correlation between clinical stage and course of disease. Changes in response to croton oil tended to precede alterations in dinitrochlorobenzene response.


Cardiac rhythm in men during cystoscopy.

Cardiac rhythm was monitored prospectively in 69 men during 191 cystoscopies. Ectopic beats from ventricular and supraventricular foci occurred in a significantly greater proportion of procedures in men with (76 per cent) compared to men without (16 per cent) heart disease. Other arrhythmias occurred to a lesser extent but there was no significant difference between men with and without heart disease. Plasma lidocaine was detected in significant amounts following intraurethral injection used for local anesthesia. Comparison of the types of arrhythmias that occurred during cytoscopy and the type of anesthetic used showed that significantly fewer ventricular ectopic beats occurred with general (8 per cent) or epidural anesthesia (13.8 per cent) as opposed to local lidocaine anesthesia (48.7 percent). Among the 3 anesthetic groups there was no difference with respect to frequency of supraventricular ectopic beats. No permanent cardiovascular complications occurred although several potentially serious dysrhythmias were seen.


Factor IX deficiency in the nephrotic syndrome: studies with prothrombin complex concentrate.

A patient manifesting acquired factor IX deficiency in association with the nephrotic syndrome received prothrombin complex concentrate and demonstrated an accelerated plasma disappearance rate of factors II, IX and X. Amelioration of proteinuria and the plasma coagulation defect followed therapy with corticosteroids and azathioprine.


Traumatic veno-caliceal fistula in a solitary kidney.

We present herein what we believe to be the first reported case of a traumatic veno-caliceal fistula and describe our technique for surgical repair. We use a transabdominal approach for renal trauma and advocate occlusion of the renal artery alone during intrarenal surgery. We believe that conservative management of renal injuries, even with a solitary kidney, yields the highest salvage rate. Initial arteriography best delineates most renal injuries and is a safe technique for following progressive changes that may require an operation. When injury occurs in a solitary kidney medical renal consultation and facilities for interim dialysis must be readily available.


Malignant pheochromocytoma of the bladder: the late development of renal cell carcinoma.

A case of malignant pheochromocytoma of the bladder associated with renal cell carcinoma is described. The necessity for long-term followup in such cases is stressed. This case provides further documentation of the association of pheochromocytoma with renal cell carcinoma, an association which may occur more frequently than would be dictated by chance alone. It is suggested that these cases may represent von Hippel-Lindau disease with incomplete penetrance.


Bilateral anorchism.

A case of surgically proved bilateral anorchism is reported. Emphasis is placed on the importance of early diagnosis and treatment in the proper management of this rare entity.


Normal paraganglia in the human prostate.

A normal paraganglion was discovered incidentally in prostatic fragments resected for nodular prostatic hyperplasia.


Tubular duplication of the rectum with a rectourethral fistula.

An infant with pneumaturia and fecaluria was found to have a rectal duplicatation with a fistula between the duplicated rectum and the urethra. Rectal duplication, although rare, should be considered in cases of bizarre lower bowel symptoms in children. Correction in our case was effected by exclusion of the duplicated segment along with removal of its mucosal lining and division of its urethral fistula. The termination of the duplicated rectum in the urinary tract, as in cases of imperforate anus, suggests a related embryologic mechanism for the 2 types of anomalies.


The use of ketamine hydrochloride as an anesthetic for raccoons.

Ketamine hydrochloride was observed to be an effective anesthetic for recently captured raccoons (Procyon lotor) when they were injected intramuscularly with 20-29 mg/kg body weight. Excellent anesthesia occurred from 5 to 15 min after injection. No respiratory difficulties were encountered. The only undesirable clinical sign was excessive salivation.


Arbovirus surveillance in Florida: wild vertebrate studies 1965-1974.

Wildlife species from 38 of Florida's 67 counties were surveyed over a 10 year period for the presence of antibody to the five major arboviruses circulating in the state. The routine screening of 7891 sera from wild birds and mammals via the hemagglutination-inhibition (H1) test with selected reactors subjected to serum neutralization testing has 1) provided information regarding geographic distribution and seasonality of circulation of these viruses 2) identified enzootic foci of infection and those species of wildlife most commonly infected and 3) documented the potential value of certain wild mammals as indicators of St. Louis Encephalitis and Venezuelan equine encephalomyelitis virus activity prior to the detection of human cases. Limited studies of Tamiami and Tensaw virus on sera from mammals collected for other purposed provided additional baseline information on the activity of these viruses in Florida mammals. Isolations of eastern equine encephalomyelitis virus were made from the heart of a loggerhead shrike (Lanius excubitor), Tensaw virus from the brain of a gray fox (Urocyon cinereoargenteus), and Keystone virus from the heart of a bluejay (Cyanocitta cristata).


Enterolithiasis in a confined Hartman's mountain zebra.

Enterolithiasis was observed on necropsy of a Hartman's mountain zebra (Equus zebra hartmannae). A single enterolith had caused obstruction and rupture of the small colon. The gross lesions are described and the possible etiology discussed.


Isolation of type a influenza viruses from the migratory waterfowl along the Mississippi flyway.

Four type A infleunza viruses were isolated from tracheal swabs taken from apparently healthy ducks (mallards, Anas platyrhynchos) along the Mississippi flyway in Minnesota. Inital identification of group A influenza was made possible by the use of the agar gel precipitin test.


Paragonimus kellicotti infection in wild carnivores in southwestern Ontario: II. Histopathologic features.

Pulmonary lesions associated with naturally acquired Paragonimus kellicotti infection were studied in mink (Mustela vison), striped skunks (Mephitis mephitis),  red foxes (Vulpes vulpes) and a coyote (Canis latrans). In ,ink a fibrous capsule was formed around mature flukes in dilated bronchioles or bronchi, and there was mild focal interstitial pneumonitis adjacent to fluke eggs in alveoli and migrating parasites. A thick wall, infiltrated heavily with mononuclear cells and eosinophils, surrounded mature P. kellicotti in skunks and an extensive inflammatory reaction was found around fluke eggs. In red foxes the wall was thin, hemorrhagic and contained little collagen; necrosis was associated with migrating parasites. Thick capsules formed by marked fibroplastic changes in the lamina propria of affected bronchi were found in the coyote.  In raccoons with pleural adhesions massive fibroplasia with eosinophil infiltration beneath the pulmonary pleura suggested a reaction to a migrating parasite entering the lung from the thoracic cavity. It was thought that immature P. kellicotti may have caused the lesion.


Haematological investigations in east African birds of prey.

Packed cell volume, haemoglobin and erythrocyte counts are given for 52 East African birds of prey of 21 species. Whilst the majority of the birds sampled were "normal", some were injured or diseased. The results are discussed and attention is drawn to the possible value of haematology in clinical diagnosis.


Absence of Anaplasma marginale infection in American Bison raised in an anaplasmosis endemic area.

Blood was collected at slaughter from 132 adult American bison (Bison bison) raised in an anaplasmosis endemic area where the vector Dermacentor andersoni (equals venustus) is indigenous. Hematologic studies revealed no indication of clinical anaplasmosis. Card agglutination and complement-fixation tests on all bison serums were negative. Eleven anaplasmosis-susceptible calves each inoculated with 204 ml of blood pooled from 12 bison did not develop anaplasmosis. Results of this study indicate American bison have resistance to natural A. marginale infection.


Spontaneous dermatophilosis in twin white-tailed deer fawns.

Twin white-tailed deer (Odocoileus virginianus) fawns captured in Morris  County, New Jersey, displayed papular, darkly pigmented scabs principally on the  skin overlying the nasal bones, dentary, commissure of the lips and ears. Histopathological and bacterial examinations revealed Dermatophilus congolensis. The epidermitis caused by this bacterium apparently had developed within the first 12 to 14 days after birth and had begun to regress by one month of age. The location of the lesions suggested transmission during nursing from an infected doe. This is believed to be the first confirmed report of this zoonotic disease in white-tailed deer, with isolation of the etiologic agent, outside the State of New York. Epizootiological considerations are discussed.


Experimental transmission of Eimeria confusa Joseph 1969 to the fox squirrel.

Eimeria confusa Joseph, 1969 from the gray squirrel Sciurus carolinensis was transmitted to the fox squirrel Sciurus niger rufiventer. This is the first report of the successful cross-transmission of a gray squirrel coccidium to the fox squirrel.


Bovine coccidia in American bison.

Three species of coccidia, found in American bison sampled in Wyoming, are identified. The described coccidial species, common to cattle, have not been reported previosuly from American bison, (Bison bison). Identification of the parasites was determined by oocyst structural measurements and by oocyst sporulation times.


Mandibular anesthesia and tooth extraction in the bottlenosed dolphin.

Anatomical dissections were done to show the innervation of the teeth and mandible of the bottlenosed dolphin (Turslops truncatus). Using structural landmarks, a method has been devised for anesthetizing the lower jaw. With this procedure teeth can be extracted and age determined by counting dentine layers in sections of etched teeth. Animals of the most desirable ages can thus be selected and the ages of animals already in captivity can be determined.


Severe parasitism in an opossum.

Chronic debilitation and anemia were observed in a free-living opossum (Didelphis marsupialis) heavily parasitized by Physaloptera turgida, Brachylaima virginianum, and Cruzia americana. Chronic interstitial pneumonia associated with Capillaria aerophila and a metastrongyloid nematode also was present.


The effect of malignant neoplasms on the heart. A study on the electrocardiographic abnormalities and the anatomical findings in cases with and without cardiac involvement.

Six hundred and twenty-two autopsies of patients with malignant neoplasm were used for this study. The incidence of cardiac involvement in relation to the sites of the primary tumor, the anatomical distribution within the heart, and the ECG findings in the patients with and without cardiac involvement were analysed. The incidence of cardiac involvement by malignant tumor was 12.7% (79 out of 622 cases). Involvement by breast and pulmonary cancer was found to be very common, while intestinal and gastric cancer uncommonly metastasised to the heart. The incidence of epicardial involvement was higher than that of the pericardium, myocardium, or endocardium. A significant difference was observed in the ECG findings recorded within 3 months before death between the groups with and without cardiac involvement. Cases of myocardial metastasis were always associated with the pattern of myocardial damage in the ECG. The findings in this study are discussed in the light of previous reports.


Hypertensive vascular lesions and renin or lysosomal enzymes in rats.

In rats treated with DOCA plus high salt or with high salt alone, hypertensive rats with renal vascular lesions showed an incomplete suppression of KRA. Cathepsin activity of rat kidney was higher under high salt loading than in the control. Beta-glucuronidase activity was greatest in rats with renal vascular lesions and smallest in rats fed on normal chow. RNase and DNase activities were greater in rats with renal vascular lesions than in rats without renal vascular lesions under high salt loading. 2) In rats of both sexes SHR showed greater KRA and cathepsin activities than WK rat under high salt loading. In female rats DNase, RNase and beta-GPase activities were greater in SHR than in WK rat under high salt loading. 3) KRA was higher in SHRSP aged 10 months than in SHRSR, though KRA of SHR was smaller than KRA of WK rat. Cathepsin activity was greater in SHRSP than in SHRSR. DNase and beta-NAGA activities were greater in SHR than in WK rat. 4) In 7 weeks of age SHRSR showed more PRC than SHRSP. At the age of 10 months SHRSP showed higher PRC than WK rat. The roles renin and lysosomal enzymes in hypertensive renal vascular lesions were discussed to some extent.


Stress as a causative factor of essential hypertension and its influence on the cardiovascular system.

Cardiovascular responses to cold stress were investigated in hypertensive patients. There were few differences in the changes under cold stress of the serum catecholamine concentration between the juvenile group and middle-aged group. In the juvenile group, a remarkable increase in TPR was observed under cold stress, suggesting that the vascular reactivity is increased and at the same time the cardiac response to inotropic action was increased under cold stress. On the contrary, in the middle-aged group, there was less increase in TPR under cold stress and no increase in inotropic action was observed. From such results, hyperreactivity to stress in the cardiovascular system is thought to be an important factor in the pathogenesis of essential hypertension. Such cardiovascular responses are seen more easily in juvenile hypertension or initial stage of essential hypertension. In the hypertensive patients after middle-age, organic changes will develop by the repeated pressure load to the cardiovascular system caused by various stimulations and the reactivity of cardiovascular system to stress becomes less manifest.


Studies on etiology of essential hypertension. Hemodynamics, water-sodium balance and response to pressor substances during long-term sodium restriction and after spontaneous blood pressure fall--.

CI, TPRI, PV, ECFV, Nae, PRA and a pressor response to NA and AT was measured before and after 1) sodium restriction and 2) spontaneous blood pressure fall (spontaneous fall) in the patients with essential hypertension and the following results were obtained. 1) CI did not change during sodium restriction and increased after spontaneous fall. TPRI was reduced and the degree of this reduction was positively correlated with that of blood pressure reduction under these two conditions. 2) Sodium restriction caused the decrease of PV, ECFV and Nae and the increase of PRA. The degree of the reduction of PV and Nae was positively correlated with that of blood pressure fall. After spontaneous fall, PV, ECFV and NAe  was increased and PRA did not change significantly. 3) A pressor response to NA and AT was depressed after one week of sodium restriction, and after 4 weeks the former returned to the basal response, while the latter was still reduced. NA response was correlated positively with basal Nae, ECFV and interstitielle fluid volume and negatively with basal PRA. AT response was negatively correlated with PRA before and during sodium restriction. No correlation was  observed, however, between the degree of reduction of blood pressure and that of the change in pressor response to NA or AT. After spontaneous fall, the response to NA was not reduced but increased. These results suggested that, although the fall in blood pressure under these experimental conditions was mediated by the reduction of TPRI, the changes in pressor response to NA and AT did not affect primarily the reduction of blood pressure.


Pathogenesis of acute arterial fat deposition in spontaneously hypertensive rats.

The selectively-bred substrains of spontaneously hypertensive rats with a greater vulnerability to vascular lesions rapidly developed arterial fat deposition within 1 or 2 weeks as well as a greater hypercholesterolemic response when fed on high fat cholesterol diet including 20% of suet, 5% of cholesterol and 2% of cholic acid. The ring-like arterial fat deposition at the branches of superior mesenteric arteries and cerebrobasal arteries, which was found to be good indices for the deposition of intrarenal or coronary arteries, was not observed in normotensive rats fed on high fat cholesterol diet for 3 months, greatly delayed in SHR under antihypertensive treatment and accelerated by 1% salt loading in drinking water. The horseradish peroxidase infused intravenously 1 to 4 hours before sacrifice leaked in ring-like forms which corresponded to the fat deposit in mesenteric arteries. The incorporation of 3H-proline infused 4 hours before sacrifice was enhanced in the mesenteric arteries with the fat deposition. These results clearly indicated that hypertension was a great contributory factor to rapid arterial fat deposition, which was caused by an increased vascular permeability and enhanced the arterial collagen formation, the initiation process of arterio- or atherosclerosis.


Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR).(1) Quantitative estimation of cerebrovascular permeability.

The cerebrovascular permeability quantitatively determined by the retention of 131I-human albumin in the perfused brains was increased in SHR, especially in stroke-prone SHR compared with normotensive Wistar-Kyoto, and confirmed the macroscopical or microscopical findings on the leakage into the brain or trypan blue or peroxidase injected intravenously 2 to 3 hours before sacrifice. The localization of increased vascular permeability in SHR corresponded to the predilection sites of cerebral hemorrhage or softening, which developed likely following the increased cerebrovascular permeability.


Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR). (2) Prophylactic effect of moderate control of blood pressure on stroke.

The offspring of male stroke-prone SHR, 80 in total, were divided into treated and nontreated groups at the age of 30 to 45 days. The former groups were treated with alpha-methyl dopa (2 g/l in the drinking water), or L-dopa (2 g/l) with or without peripheral decarboxylase inhibitor (MK-486, 1-3 g/l) or apresoline (0.08 g/l) thereafter till they died a natural death during 1  and a half year observation period. So far as hypertension was controlled under about 210 mmHg, no stroke was observed, while nontreated group developed cerebrovascular lesions spontaneously in about 80 per cent. This study experimentally confirmed the importance of blood pressure control for the prevention of stroke.


[Study on myocardial carbohydrate and energy metabolism during exercise in patients with circulatory diseases (author's transl)].

1. In thirty six patients with various circulatory diseases, the influence of exercise on myocardial carbohydrate metabolism was observed by use of coronary sinus catheterization. Bicycle ergometry was performed in supine position at a level of fifty watts for fifteen minutes. 2. The myocardial carbohydrate metabolism was not significantly affected by the manipulations with coronary sinus catheterization. 3. At resting state, there was no significant difference among disease groups except that myocardial lactate extraction ratio showed lower values in some cases of the patients with coronary heart disease. 4. During exercise, in cases of neurocirculatory asthenia and hypertension without coronary insufficiency, the myocardial carbohydrate usage was increased with the increase in coronary blood flow and the arterial concentration, maintaining of the carbohydrate extraction ratio. In cases of hypertensive coronary failure, the myocardial carbohydrate usage was maintained chiefly with remarkable increase in the arterial concentration in spite of no significant change of coronary blood flow and the carbohydrate extraction ratio. In normotensive coronary heart disease, the myocardial carbohydrate usage decreased or slightly increased, chiefly due to strong decrease in the extraction ratio and to the lowest increase in coronary blood flow. In many cases the carbohydrate release out of the heart muscle was observed. For the most of the cases of the other heart diseases, the latent disturbance of myocardial carbohydrate metabolism was revealed by exercise in spite of the good response of coronary circulation. 5. The myocardial uptake, extraction ratio and usage of lactate were significantly lower in the ischemic ECG positive group than in the negative group, in spite of significantly higher increase in the arterial concentration in the positive group. The myocardial metabolism of pyruvate during exercise was similar to that of lactate, but the myocardial metabolism of glucose was not clearly correlated with ECG changes.


Anterior mitral valve echo in patients with isolated ventricular septal defect and with tetralogy of Fallot.

Eight patients with isolated ventricular septal defect and two patients with tetralogy of Fallot were studied by UCG. Two of these patients showed notchings and five showed flutterings on F-A portions of the anterior mitral leaflet echoes. Fluttering seemed to be recorded more frequently in patients with right-to-left shunts such as cyanotic tetralogy of Fallot. It was considered that these functional changes of mitral valve echoes during diastole would be caused by the direction and amounts of blood flow across the defect and the velocity and amounts of blood flow through the mitral valve. Fluttering of mitral valve echo during diastole may be observed in normal subjects or in patients with other cardiac abnormalities, such as aortic insufficiency, atrial fibrillation or flutter. Flutterings seen in ventricular septal defect and tetralogy of Fallot are, however, of low amplitudes and of high frequencies, and are observed mainly between F and A points.


Cardiopulmonary dysfunctions caused by ADP-induced platelet aggregation.

Intravenous (i.v.) injection of 0.1 mg/kg of ADP within one second in 13 rats caused a prompt drop in platelet count to 55.1 plus or minus 3.2% of the preinjection value with a statistical significance (p less than 0.01) at 30 seconds after the injection. At that time, mean arterial pressure and arterial PO2 decreased, while central venous pressure increased. Heart rate decreased with an appearance of sinus bradycardia and variable A-V block. Various respiratory effects such as shallow or slow respiration or apnea appeared. Such changes showed a tendency to recovery within 3 minutes. Splenectomy did not prevent these changes in 6 rats. In 6 thrombocytopenic and leukopenic rats treated with busulfan, these changes did not appear. Intra-arterial injection of the same amount of ADP induced almost no response. When ADP was injected twice 20 seconds apart in 10 rats, the second injection resulted in no effects or slight responses. In contrast, when 10 rats were injected twice 180 seconds apart, both the first and second injections showed the same effects on platelets and cardiopulmonary functions. The results suggests that the effects observed following I.V. ADP are probably due to transient obstruction of coronary and pulmonary microvessels by platelet aggregates. Reduced response following two successive injections may be due either to the reduced platelet count or to a refractory state induced by the first injection. ADP is probably rapidly metabolized in systemic microvascular beds.


[Correlation of external cardiac indices with internal parameter of left ventricular function in hypertension and ischemic heart disease (author's transl)].

An indirect and direct estimate of the left ventricular performances were compared in 45 patients with hypertension, arteriosclerotic heart disease and miscellaneous diseases. In results, externally measured LVET, ET/PEP, PEP and a wave ratio correlated well with internally measured myocardial function. Therefore it was concluded that this convenient and atraumatic method was useful as a valid and sensitive measure of myocardial performance.


[Evaluation of ototoxicity of amikacin (BB-K8) by animal test (author's transl)].

Seventy Hartley strain guinea pigs (350 g body weight at start of the experiment) were used. BB-K8, gentamicin (GM) and kanamycin (KM) were given to the animals intramuscularly for 28 days at following various doses: (see article) These guinea pigs underwent a differential frequency pinna reflex test in wide frequency range from 20KHz to 0.5 KHz before the administration, during the injection and after the last one. For histopathological examination of the inner ears the guinea pigs were subjected to intravital fixation with Wittmaack's fixative under nembutal general anesthesia. Blocks including the bilateral temporal bones were removed from the skulls and then fixed in the same fixative for 1 similar to 2 weeks. After routine procedure for decalcification, dehydration and celloidin embedding, horizontal serial sections of the inner ears were made and stained with hematoxylin-eosin. The differential frequency pinna relfex test in the 70 guinea pigs indicated positive pinna reflex in 90% at 20KHz and in 100% at 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5 KHz before start of the administration. Administration of the antibiotics for 28 days occasionally resulted in the pinna reflex loss which always involved the highest frequency, 20 KHz and then was followed in relatively regular succession by 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5 KHz (Tables 1 similar to 8). On the other hand, histopathological examination of the inner ears disclosed that the loss of the outer hair cells in the spiral organ which are the most sensitive to the ototoxic antibiotics, occurred always at the basal end of the spiral organ and then spread from there to upper portion of the spiral organ (Tables 9 similar to 16). Based on the differential frequency pinna reflex test in the wide frequency range and extensive histopathological examination of the inner ears, ototoxicity of BB-K8 is considered to be more mild than GM. However, there was not so remarkable difference in ototoxicity between BB-K8 and KM in the present experiment. The result or examination of the guinea pigs received BB-K8 at 40 mg/kg and 100 mg/kg respectively for 28 days suggests that BB-K8 at expecting clinical dose, 500 mg per day (for 28 days) may be safe from ototoxicosis in the inner ears. In the vestibular organs of the animals received BB-K8 there was no decrease in number of the hair cells.


[Experimental studies on absorption, distribution and excretion of fosfomycin. I. Absorption distribution and excretion of fosfomycin calcium salt (author's transl)].

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((minus)-cis-1,2-epoxypropylphosphonic acid) which is a new antibiotic, the absorption, distribution and excretion were studied when it was administered orally to fasted test animals such as rats, rabbits and dogs. The results are as follows: 1) In the case of rats, the more dose size was increased, the more ratio of excretion in urine as index of gastrointestinal absorption was reduced and ratio of excretion in stools was adversely increased, which suggested a decrease in absorption efficiency. But, as absolute amount of excretion in urine became larger with dose size, it was considered that increase in dose size would serve for elevation of serum levels. 2) When the calcium salt was given to rats and rabbits in form of solution and suspension, the former was more eminent than the latter regarding to absorption efficiency, as generally known. The solution, however, needed relatively large quantity of water to solubilize the calcium salt, and it was not considered that the absorption efficiency depends on only dissolution step or dissolution rate. 3) Difference of the particle size varying from 1.50 mu(bulk particle size) and 0.64 mu(mechanical limit size) measured by Kozeny-Carman method did not affect on the absorption in rats and dogs. So it was considered that the bulk could be use directly without micronizing in manufacturing process for the oral preparations. 4) There were some differences of absorption among the animal species. Good absorption was shown in turn in rats, dogs and rabbits. These differences might depend not only on physiological factors but also anatomical differences such as length of gastrointestinal tract. 5) In rabbits high concentration was observed successively in kidney, lung, heart and so on. In any organ its level decreased similarly to the serum level, not sustaining its initial high concentration. The calcium salt did not possess any affinity to certain organs. 6) In conclusion, though some differences of gastrointestinal absorption were observed among the animal species, fosfomycin calcium salt was well absorbed without problem of micronizing the bulk particles. Moreover, it was perceived that fosfomycin calcium salt, once distributed, would not remain in particular organs, being excreted out of body.


Experimental studies on absorption, distribution and excretion of a new antibiotic, fosfomycin. II. Absorption of oral preparations of fosfomycin calcium salt in dogs (author's transl).

To establish the best usage and dosage of fosfomycin granule and capsules which had been prepared based on our fundamental experiences as described in the first report, absorption of calcium salt contained in both preparations was evaluated using dogs as test animals. (1) Granule containing the calcium salt equivalent to 200 mg of fosfomycin free acid per g showed almost the same absorption as the bulk (fosfomycin calcium), having no disadvantage due to processing. (2) Capsules containing the calcium salt equivalent to 250 mg and 500 mg of the free acid per capsule showed slightly more retarded absorption than the bulk, probably due to some inevitable factors such as disintegration rate of capsules and dispersion rate of the calcium salt. But, once dispersed, the calcium salt in capsules was well absorbed as well as the bulk material. (3) Gastrointestinal absorption of granule and the capsule contents was almost the same. (4) Simultaneous administration of capsules and water improved the absorption efficiency. Though administration after feeding caused somewhat retarded absorption of the drug, the serum levels were rather well sustained with a slight drop but sufficiency of absorption, suggesting better clinical advantages than in the fasted animals. (5) Fosfomycin calcium salt in both preparations was well absorbed in the test animals through gastrointestinal tract as well as the bulk calcium salt, without any possible disadvantage caused by processing. In addition, the absorption efficiency was improved by giving with water or meal to the animals.


[Clinical experience with ampicillin-cloxacillin (Rectocillin 'Kyowa') in uroloigcal field (author's transl)].

Ampicillin-cloxacillin (Rectocillin 'Kyowa') was administered either orally (capsules) or by intravenous drip infusion to a total of 40 patients and the following results were obtained: 1. Effectiveness obtained in the group received Rectocillin capsules (1,500 mg/day) was 80%. 2. Effectiveness obtained in the group received Rectocillin intravenous drip infusion (3 similar to 10 g/day) was 64.7%. 3. Side effects were encountered in 2 of 40 patients, but none of them were serious, and clinical abnormalities due to this antibiotic were not observed.


[Clinical study on amoxicillin in otorhinolaryngological field (author's transl)].

Clinical effect of amoxicillin was evaluated in 29 cases of the acute infections of ear, nose and throat: 8 cases of acute purulent otitis media, one case of acute otitis externa, one case of furuncle of the ear, 2 cases of acute sinusitis, 12 cases of acute lacunar tonsillitis, 2 cases of pharyngolaryngitis, one case of acute cervical lymphadenitis, one case of phlegmon of the face and one case of acute gingivitis. The following results were obtained from the clinical and laboratory studies. 1) The therapeutic results were excellent in 18 cases, good in 5 cases, fair in 3 cases and poor in 3 cases. The effect was observed in 79.3% of the patients treated. 2) The causative bacteria were: 3 strains of beta-Streptococcus hemolyticus, 4 strains of Hemophilus, 4 strains of Staphylococcus aureus, one strain of Diplococcus pneumoniae, one strain of Gram-positive Diplococcus and Gram-negative Bacillus. Clinically good results were obtained in patients infected with beta-Streptococcus hemolyticus, Hemophilus and Diplococcus pneumoniae. 3) No side effect was observed with amoxicillin, except slight diarrhea in one case. This side effect disappeared by cessation of the administration. 4) No unfavourable influence was noticed on peripheral blood, liver function nor renal function by administration of amoxicillin. 5) From the results of this series, amoxicillin seems to be useful in the treatment of acute infections of the ear, nose and throat.


The effect of dipyridamole on the coronary hemodynamics in man.

The effects of dipyridamole (Persantin) on the coronary blood flow (the great cardiac vein flow and coronary sinus ostial flow), the femoral arterial pressure, the coronary vascular resistance and the heart rate were measured continuously in man. The newly devised method of the continuous local thermodilution method enabled us to perform the exact measurement of the above mentioned variables in man. The increase of the coronary blood flow was seen definitely in the non-ischemic group and, therefore, the decrease in the coronary vascular resistance occurred in 30 sec and continued for more than 20 min. In the myocardial ischemic group, some patients showed the similar response to the non-ischemic group. However, some patients showed no increase of the flow, even though the coronary vascular resistance decreased in all cases in this group. The heart rate increased slightly in all cases.


Ultrasonic diagnosis of ventricular aneurysm.

Fifteen patients with ventricular aneurysm were selected based on the following 3 criteria: 1) electrocardiographic evidence of old myocardial infarction, 2) presence of abnormal precordial impulse, 3) presence of dyskinesis or akinesis with diastolic bulging of the ventricular cavity by angiocardiogram. Eight patients had anterior left ventricular aneurysm and 7 apical aneurysm. The characteristic abnormal precordial impulse was diminished or absent A wave, pre-upstroke retraction, late systolic bulge, and diminished rapid filling wave, all of which were recorded over the restricted area of the broad precordial impulse. M-mode echocardiogram revealed increased or normal excursion of the posterior left ventricular wall. However, abnormal motion of the anterior left ventricular wall was detected in all, if the transducer was located over the abnormal precordial impulse or slightly inside of it. Compound M-mode echocardiographic scan toward the abnormal precordial impulse was able to detect asynergy of the anterior left ventricular wall and the apex, and distinguish it from motions of the interventricular septum and the anterior right ventricular wall. Abnormal motion of the anterior left ventricular wall was paradoxical in 13 patients and flat in the others. Systolic posterior mortion of the posterior left ventricular wall was detected in 2 patients with apical aneurysm. Cardiac ultrasonogram scanning over the abnormal precordial impulse demonstrated the bulging of the ventricular cavity in either systole or diastole depending on the site of lesion. There was a good correlation between cardiac ultrasonography and angiocardiography with respect to the site of lesion. Our study indicates that this method is useful in the diagnosis of anterior and apical aneurysm which ordinary technique failed to detect.


Effect of pressor agents on blood pressure, plasma renin activity and plasma aldosterone concentration in essential hypertension.

The responses of blood pressure, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) to infusion of either angiotensin II (10 ng/Kg/min) or norepinephrine (100 ng/Kg/min) were observed in 25 patients with essential hypertension. The difference in modes of response between low renin essential hypertension and normal or high renin essential hypertension was analyzed. For comparison, 5 patients with Conn's syndrome, 4 with renovascular hypertension, and 5 normotensive subjects were also studied. Following infusion of antiotensin II the changes in diastolic blood pressure (DBP) were +24+/-3.0 mmHg in low renin essential hypertension and +25+/-3.1 mmHg in normal or high renin essential hypertension in PRA -0.28+/-0.06 ng/ml/h in low renin essential hypertension and -0.69+/-0.02 mg/ml/h in order and in PAC +3.7+/-1.4 and +7.6+/-1.8 ng/100 ml respectively. There was a significant difference in magnitude of response in PRA between the 2 groups of essential hypertension (p  less than 0.05). Norepinephrine induced rise in DBP with decreases both in PRA and PAC. The mean changes in DPB were +6+/-1.4 mmHg in low renin essential hypertension and +16+/-2.2 mmHg in another and the pressor response in the later was significantly greater (p less than 0.01). The changes in PRA were -0.14+/-0.07 ng/ml/h in low renin essential hypertension and -0.67+/-0.26 ng/ml/h in normal or high renin essential hypertension, and in PAC -4.9+/-1.3 and -3.3+/-1.9 ng/100 ml respectively. The greater fall in PRA in normal or high renin essential hypertension was observed but the difference between the 2 groups of essential hypertension was not significant. The changes in PAC did not parallel the changes in PRA. Angiotensin II indcued essentially similar effects on blood pressure in both groups but the greater feedback inhibition of PRA was produced by this peptide in normal or high renin essential hypertension than in low renin essential hypertension. Norepinephrine induced significantly greater pressor effect in normal or high renin essential hypertension. The adopted dose of norepinephrine suppressed both PRA and PAC and a tendency to the greater fall in PRA was observed in normal or high renin essential hypertension. There was no difference in responses of PAC to both agents between the 2 groups of essential hypertension.


Effects of ethyl adenosine-5'-carboxylate on the heart and coronary circulation.

Using the canine heart-lung preparation supported by a donor, the effects of ehtyl adenosine-5'-carboxylate (EAC) on the heart and coronary circulation were studied and compared with those of adenosine. EAC produced qualitatively similar effects to adenosine in this preparation. Aminophylline inhibited the effects of EAC as well as those of adenosine. Dipyridamole did not potentiate the effects of EAC, while it produced a definite potentiation of the effects of adenosine.


Relationships of left ventricular systolic time intervals with hemodynamic variables in intact and failing hearts.

Deviation of systolic time intervals (STI) from the regression lines obtained from 122 normal subjects was studied in 22 healthy adults (Group 1), 18 N.Y. functional class I cardiac patients (Group II) with ischemic (IHD) or primary myocardial disease (PMD), and 15 similar patients (pts) but N.Y. functional class II with prior heart failure (Group III). STIc (corrected for heart rate) were normal in Groups I and II. Supine exercise caused shortening of pre-ejection period PEPc and prolongation of left ventricular ejection time ETc in both groups. Group III pts had a significantly longer PEPc and shorter ETc at rest. Supine exercise caused further prolongation of PEPc and a slight prolongation of ETc in this group. In 8 mongrel dogs, the effect of controlled changes of hemodynamic variables on STI was studied with intact hearts and repeated after myocardial impairment has been induced by pentobarbital. Doubling of venous return while the heart was intact produced changes in STI similar to the effects of supine exercise in Groups I and II human subjects. With myocardial impairment, comparable increase in venous return had an effect on STI similar to the effect of supine exercise Group III patients. Controlled increase in each of heart rate or blood pressure, with other hemodynamic variables kept constant, produced changes in STI different from the effect of supine exercise on human subjects. The study suggests that the value of supine exercise induced changes in STI in reflecting left ventricular performance is attributable primarily to increased volume load. In this resepct supine exercise is probably superior to other forms of exercise in disclosing impaired left ventricular performance.


Hypertension-inducing potency and renin content of variously treated kidney extract.

Kidney extract from rats which were adrenalectomized and given tap water was dialyzed, salted out, ultrafiltrated or heated. A given dose of each extract or fractionized material was administered to uninephrectomized rats subcutaneously every 12 hours for 10 days. The relationship between renin content of each sample and final blood pressure level following repeated injections as an index of its hypertension-inducing potency was analyzed. There was no apparent discrepancy between the two of each sample. No evidence was obtained for the existence of other renal substance than renin which might be implicated in producing hypertension.


The incidence of myocardial infarction in hospitalized patients and the risk factors of myocardial infarction.

1) Patients with myocardial infarction constituted 2.36% of all the hospitalized patients during 1961-1968. The mortality of the hospitalized patients with myocardial infarction during the same term was 19.1%. The ratio of the male to female patients with myocardial infarction was 5.2. 2) As the risk factors of myocardial infarction, the following items were considered to be of importance: 1. gout in past history, 2. angina pectoris in family history, 3. diabetes mellitus in family history, 4. cigaret smoking over 40 pieces per day, 5. diabetes mellitus in past history, 6. administrative occupation, 7. serum cholesterol level over 250 mg/100 ml, 8. obesity of 20% excess over standard body weight, 9. hypertension in family history. 3) According to the statistical analysis, several groups of risk factors and interrelationship of risk factors are recognized.


A family of Holt-Oram syndrome.

A family of Holt-Oram syndrome is reported. Twenty of 41 living members in the last 3 generations were examined. The propositus expressed typically the cardinal features of this syndrome: atrial septal  defect, patent ductus arteriosus, cardiac arrhythmias and conduction block of various types, and hypoplasia of the left thumb. Two individuals were clinically diagnosed to have atrial septal defect without any upper limb anomaly, and 3 showed upper limb anomaly without any sign of congenital heart disease. Other 5 members showed only minor abnormalities, such as funnel chest or mild right ventricular hypertrophy on ECG and VCG. Some of the skeletal abnormalities observed were hitherto undescribed ones. These include generalized hypoplasia of left hand and downward displacement of right sterno-clavicular joint.


Staphylococcal footpad infection in mice.

Local footpad infection in mouse was investigated with 55 clinically isolated strains of Staphylococcus aureus. When 10(7) viable cells were inoculated into the footpad, local swelling and bacterial growth resulted after 24 hr. With a dose of 10(6) cells, moderate swelling was observed after a few hours but the reaction had almost disappeared after 24 hr. About 75% of the staphylococcal strains tested caused footpad edema in mice at doses of 10(7) cells. A statistical comparison of the virulence of the organisms on intravenous and intraperitoneal injection with that in inducing footpad swelling is also reported.


Excitability of crayfish giant axons in sodium-free external media containing hydrazinium, hydroxylamine, or guanidinium ions.

Giant axons of crayfish were excitable in sodium-free external media containing hydrazinium, hydroxylamine, or guanidinium ions. Action potentials in these solutions were slightly smaller in size and a little longer in duration than those in standard Harreveld's solution. The resting potential was not affected in hydrazine or in hydroxylamine saline, but decreased in gaunidine saline. The membrane potential at the peak of the spike (V) was plotted against the univalent cation concentrations in the external medium. The relationship could be expressed by an equation: V = VO + (RT/F) ln ([Na] + alpha[C]), where VO and alpha are constants and [Na] and [C] are concentrations of sodium ions and the tested cations, respectively. The parameter alpha was considered as an indicator to express the ability of substitution of the cation for sodium ion. The order of the ability of the substitution was Hydroxylamine greater than Hydrazinium greater than Guanidinium greater than Choline.


A comparison of thermoregulatory responses in the Japanese macaque (Macca fuscata) and the crab-eating macaque (Macaca irus) during cold exposure.

Thermoregulatory responses in four male adult Japanese macaques and four male adult crab-eating macaques, weighing 6-12 kg and 6.2-8 kg, respectively, were compared at ambient temperatures (Ta) ranging from 5 degrees C to 25 degrees C. The average values +/- S.E. for some physiological measurements made at Ta of 25 degrees C in the Japanese macaque and the crab-eating macaque, respectively, were as follows: resting metabolic rate; 47.6 +/- 5.0 and 42.5 +/- 1.7 W/M2; tissue conductance; 11.9 +/- 0.8 and 8.9 +/- 0.8 W/M2/degrees C; respiratory evaporative heat loss; 4.1 +/- 0.3 and 3.2 +/- 0.5 W/M2; rectal temperature; 38.6 +/- 0.1 and 37.4 +/- 0.2 degrees C; mean skin temperature; 34.0 +/- 0.3 and 31.2 +/- 0.1 degrees C. When Ta was lowered stepwise from 25 degrees C to 20, 15, 10, and 5 degrees C successively, and maintained constant at each temperature level for 1 hr, metabolic heat production graudually increased in both species. Whe Ta was lowered from 10 degrees C to 5 degrees C, the crab-eating macaque did not show further increase in heat production and the result was a loss of thermal equilibrium with rectal temperature continuing to fall. On the other hand, the Japanese macaque maintained thermal balance even at Ta of 5 degrees C. Tissue conductance, which was significantly higher in the Japanese macaque than in the crab-eating macaque at Ta of 5, 15, and 25 degrees C, decreased in both species at Ta was lowered from 25 degrees C to 15 and 5 degrees C. The specific differences in thermo-regulatory responses are considered to be adaptational, relative to the natural habitat of thw two species studied.


Physiological comparison of the longitudinal and circular muscles of the pregnant rat uterus.

A comparative investigation of the longitudinal and circular muscles in the pregnant rat uterus (10-15 days) was made by means of electrical and mechanical recordings. The response of the circular muscle strip was characterized in the following respects: application of stretch caused acceleration of spontaneous activity that was greater in extent than in the longitudinal muscle strip; tetanic contraction was not produced by repetitive stimuli in the range of 0.1-5 Hz; slow potential was dominant in the circular muscle cells. The longitudinal contraction of the uterine segment occurred in synchronization with the change in the intraluminal pressure. Either the longitudinal stretch or the increase in the intraluminal volume caused the acceleration of synchronized activity. Stimulation of the longitudinal muscle caused membrane response in the circular muscle cells and vice versa, suggesting electrical interference between longitudinal and circular muscle cells.


Effects of short and long term exercise on intracellular glycogen and fat in pigeon pectoralis.

In an attempt to determine the functional role of the component broad white and narrow red fibre types during activity, the pectroalis muscle of the adult pigeon (Columba livia) was electrically stimulated in situ after anaesthetizing the birds with sodium pentobarbital. For examination of the effect of short term exercise, the pectoral muscle of one side was stimulated through the innervating brachial plexus, using an electronic stimulator for 1 hr, and a biopsy sample was taken from the stimulated muscle. The stimulation was resumed for 17 hr more with additional doses of anaesthesia, and a muscle sample was taken after the decapitation of the birds in the long term experiment. Muscle samples from non-stimulated pigeons under identical conditions served as control. Fixed and frozen sections were made from the samples and were stained with Periodic Acid-Schiff's reagent for the demonstration of glycogen, while additional frozen muscle sections were stained with Fettrot 7B according to Pearse, A.G.E. (1960) for the demonstration of neutral lipids in the specimen. Thus histochemical examinations were made to study effects of short and long term exercises on energy stores in skeletal muscles. Short-term stimulation resulted in a selective depletion of intracellular glycogen stores from white fibre populations whereas prolonged long term stimulation resulted in the resynthesis of glycogen within these fibres and a concomitant reduction in the intracellular fat and glycogen reserves in most red fibres. It is postulated that during flight the white fibres indulge only in brief bursts of intense phasic activity such as in quick take-off, rapid accelerations or sudden manoeuvres and utilize glycogen as fuel whereas the red fibres perform sustained activity as in cruising flight and metabolize chiefly fat.


Microphotometric method for measuring the oxygenation and deoxygenation rate in a single red blood cell.

A new reaction apparatus combining a microscope and a photometric device was developed for kinetic studies of a single red cell. A monolayer of red cells was placed in a closed reaction cuvette set on a microscope stage, a light beam of 5 to 10 mum in diameter was directed into one of the red cells, and the light transmission change in the cell was analyzed. The light beam with a wavelength range shorter than 460 nm was made by placing a narrow iris diaphragm in the light path. The space in the cuvette prevented the red cells from drying thereby providing favorable physiological conditions during measurements. The cuvette was filled with reagent gas mixtures of O2, CO2, and N2 which came in contact with the red cells. Transmission change due to the reaction was detected separately at two wavelengths of 418 and 402 nm by means of two photomultipliers mounted on the microscope. The linearity was tested by comparison between SO2 measured with a Van-Slyke apparatus and the microphotometer. Both SO2 measurements agreed well with each other, but the latter was about 3% greater than the former at around 50% SO2. Using this apparatus the oxygenation and deoxygenation velocities were measured over an entire O2-saturation range. The velocity factors showed good agreement with those obtained by using conventional flow methods.


Studies on pharmacological and biochemical properties of deamino-dicarba-[GLY-7]-oxytocin  (Y-5350).

Pharmacological and biochemical properties were investigated on deamino-dicarba-[Gly-7]-oxytocin (Y-5350). This is a newly developed compound, in which the disulfide bond and [Pro-7] of deamino-oxytocin are substituted by an ethylene linkage and glycine respectively. Bioassayed Y-5350 exhibited 202.6 u/mg of oxytocic activity, 4.6 u/mg of avian depressor activity, 441.2 u/mg of rat milk-ejecting activity and 0.02 u/mg of rat antidiuretic activity, however, adepressor activity was also evident in rats. In particular, the diuration of antidiuretic activity was short. Moreover, the oxytocic activity in pregnant rats and rabbits was weak in comparison with oxytocin. Cumulative dose-response studies were carried out on the isolated rat uterus using van Dyke-Hasting solution. The intrinsic activity was the same level as that of oxytocin, and the pD2 value was 8.62. Oxytocic activity was much enhanced by the existence of 0.5 or 2mM magnesium ion in vitro. However, the agreement between in vivo and in vitro oxytocic activity was not complete when assay was carried out in the prescence of 2 mM magnesium ion. Oxytocin was inactivated by the serum of pregnant women. In the experiment using rats, oxytocin was also destroyed by the extracts of uterus, kidney and liver. In contrast, Y-5350 was not destroyed by any of the enzyme solutions mentioned above.


Effect of ascofuranone on serum lipids of rats fed a cholesterol rich diet.

Ascofuranone, a fungal metabolite, significantly reduced serum lipid levels, when orally administered to male Wistar rats fed a cholesterol rich diet. The treatment also resulted in a marked reduction of hepatic and cardiac cholesterol contents without affecting the body weight gain. The serum albumin/globulin ratio increased significantly in the treated rats. This increase is presumably due to the decrease of beta-lipoprotein. The mode of action differentiates from clofibrate in so far as the former effectively prevents hepatic and cardiac cholesterol deposits in the cholesterol feeding rats.


Inflammation of the skin. I. Phospholipid metabolism in some experimental inflammations of mouse skin.

Phospholipid metabolism in inflamed tissue of the mouse skin which had been induced by the application of 1-chloro-2, 4-dinitrobenzene (DNCB), croton oil, or irradiation of ultraviolet rays was examined, and it was found that phospholipid levels had increased in theinflamed tissues. In the case of ultraviolet rays, the increase was temporary, and the level returned to that of control after 3 or 4 days. In the case of DNCB or croton oil, the level increased after a decrease for a short period. The pattern of the increase between physical and chemical irritation was different. Increase of incorporation of 32-P into phospholipid in inflamed tissue was examined, and it was observed that the level reached a maximum after one day. It is thus assumed that phospholipid plays an important role in the mechanism of inflammation.


Junction potentials in response to ortho- and anti-dromic stimulation of hypogastric nerve in mouse vas deferens.

The interaction of the junction potentials in response to ortho- and antidromic hypogastric nerve stimulation in mouse vas deferens was studied, using an extracellular recording method. Ortho-dromic repetitive hypogastric nerve stimulation (10 Hz, 5 min) simultaneously depressed the amplitude of the junction potentials in response to both ortho- and anti-dromic hypogastric nerve stimulation (post-te-tanic depression). No time-lag in recovery from the post-tetanic depression was observed between the junction potentials recorded from two separate electrodes, indicating that the proximodistal axonal flow of available transmitter was not involved in the recovery process. Double shocks, with intervals from 10 msec to 1 sec, were applied to the hypogastric nerve. The junction potentials in response to ortho- and ortho-dromic or anti- and anti-dromic double shock were markedly facilitated. On the contrary, the junction potentials in response to ortho- and anti-dromic double shocks were not facilited. The findings indicate that facilitation of the junction potentials is produced by the impulses propagated in the same direction along the terminal axon and also that the origin of the facilitation may be at a pre-junctional site.


Effects of puppet therapy on palmar sweating of hospitalized children.

The study investigated effects of a puppet presentation on anxiety levels of hospitalized children as measured by the Palmar Sweat Index (PSI); Subjects were 43 children, ages 5-8 years inclusive, allocated randomly to treatment and nontreatment groups. Treatment consisted of a puppet show designed to familiarize patients with hospital routines and with procedures of their operations. Four PSI measures were collected from each subject, and average difference scores of individuals among all measures were compared. Analyses of variance were used to test mean differences with data categorized by treatment, by sex, and by interaction of sex and treatment, The treatment was associated with a significant reduction in anxiety from the time of admission to both (1) the period immediately after the puppet show, and (2) the evening after surgery. In the interim, the measure of anxiety returned to near the level at admission.


Indicators of internal dose of lead in relation to derangement in heme synthesis.

Simultaneous measurements of Pb-B, Pb-U, chelatable lead, ALA-U and EP have been made in a group a asymptomatic children with increased lead absorption. Although the group is small, the results are internally consistent and show linear dose-effect relationships between Pb-U and chelatable lead (indicators of dose) and ALA-U and EP (indicators of lead's effect on heme synthesis). The data show, however, that Pb-B in a rather narrow range (48-68 mug Pb) is not a reliable indicator of the internal dose of lead. These results, as well as others, raise questions concerning the validity of relying exclusively on Pb-B in the clinical management of groups such as young children in old houses and lead-exposed workmen who are at increased risk for plumbism; The results suggest that chelatable lead is most closely related to lead's inhibitory effect on heme synthesis and that, biologically, it may serve as the best "chemical biopsy" of soft tissue lead concentration; A simple AAS method for measureing chelatable lead in urine is described; A new wet digestion technique which is compatible with ASV is also described. EP is apparently a better predictor of chelatable lead than Pb-B. Micro tests for EP, especially the zinc protoporphyrin fraction, are simple and highly useful in monitoring long-term trends in soft tissue levels in individual patients.


[Use of aldactone-saltucine in patients with heart failure].

Aldactone-saltucine was used in 52 patients with Stage IIB-III cardiac failure. The efficiency of the drug was evaluated by the dynamics of the clinical course, diuresis, body weight, blood and urine levels of electrolytes, and in some patients by the urine excretion of aldosterone. Aldactone-saltucine is a sufficiently effective diuretic agent that, without producing excessively fast diuresis, exerts after a course of therapy a beneficial effect, increasing mainly natriuresis, without concomitant hypokalemia. The diuretic effect of the drug ensued irrespectful of the initial level of urine aldosterone excretion. After a course of treatment urine aldosterone excretion tended to increase. Hyperaldosteronuria was noted in only 1/3 of the patients.


[Use of aldactone-saltucine for patients with chronic circulatory insufficiency].

In 50 patients with congestive heart failure a compound diuretic drug aldactone--saltucine was used. Diuresis, urine excretion of sodium and potassium, rate of glomerular filtration and tubular reabsorption of water, as shown by endogenous creatinin, were measured in all patients. In 13 patients the study was conducted dynamically in 8 three-hour portions of urine during 24 hours. In 6 patients the drug was administred in combination with furosemid. In 11 patients the effect of several days of therapy with aldactone-saltucine upon the urine excretion of electrolytes and their plasma level was studied. The effect of the compound drug was evaluated separately in patients with IIA, IIB and III stage of circulatory insufficiency. Aldactone-saltucine was shown to execute a distinct diuretic and natriuretic effect that lasts for 24 hours after a single dose. The drug has also a clear potassium-preserving action that manifests itself in a low level of potassium excretion with urine and an elevation of a potassium plasma level. A combination of aldactone-saltucine with furosemid considerably increases diuresis and natriuresis, without any signifcant increase in potassiuresis, which permits to use these drugs in the severest cases of congestive heart failure.


[Tolerance of physical stress and evaluation of work capacity of persons with functional diseases of the heart].

The examination of 112 patients with functional cardiopathies demonstrated that bicycle ergometry permits to differentiate them from ischaemic heart disease. These patients exhibit a reduced capacity for physical labour caused by several factors (among them such as lack of habit of physical labour, nervous regulation disorders, latent circulation insufficiency). Ergometry proves to be a good objective test for the efficiency of therapy of functional cardiopathies.


[Tolerance of physical exercise in angina pectoris].

Bicycle tests were used in 250 patients suffering from angina pectoris. The exercise was practised until the prodromal signs of an anginal seizure appeared. The mean values of exercise causing an anginal seizure appeared to be equal to 5.1 plus or minus 0.26 kgm/kg in angina decubitus and angina of effort; 11.9 plus or minus 0.67 kgm/kg is cases of daily seizures of angina of effort; 20.8 plus or minus 0.85 kg/kg in cases of several seizures a week after increased physical exercises, and 29.0 plus or minus 2.21 kgm/kg in cases of rare seizures (once a week or less frequently). This permits to believe that in cases of angina pectoris difficult of diagnosis its severity can be made precise by means of bicycle tests. The physician's assessment of the severity of angina is influenced by the physical activity of the patient in everyday life.


[Atrio-ventricular dissociation].

Cardiac rhythm disorders called atrioventricular dissociation, especially the so-called dissociation with interference have been causing controversy among the cardiologists for a long time. The latter term implies an independent activity of the atria and ventricles, that is in no way connected with an orthograde atrioventricular block, and that develops in the presence of intermittent normal conductivity of sinus impulses. This disorder is always of a secondary nature and it may be due to the disorders in the formation of the primary rhythm, or conductivity of the impulse (passive form), or acceleration of the secondary rhythm (active form). The causes of such atrioventricular dissociation may lie in sinus bradycardia, sinoauricular or incomplete atrioventricular block, compensatory pauses after extra-systoles, atrioventricular and ventricular tachycardia (paroxysmal or nonparoxysmal) with a retrograde atrioventricular block, etc.  Examples of ECG patterns illustrating most of the above mechanisms are presented. Due to the existence of several mechanisms that cause atrioventricular dissociation, and due to the fact that individual authors imply different meanings by the term "interference", it seems reasonable to abandon the term "dissociation with interference". In such case it would seem more appropriate to call the state a primary rhythm or conductivity disorder indicating an incomplete atrioventricular dissociation for a proper choice of therapy.


[Activity of the dehydrogenases of the myocardium and lymphocytes in experimental hypoxia].

The activity of succinatedehydrogenase, mitochondrial alpha-glycerophosphatedehydrogenase and NADH2-diaphorase was studied cytochemically and histochemically in the myocardium and lymphocytes of rats and mice after the effect of hypoxia in a hyperbaric chamber. A short-duration effect of hypoxia and step-wise adaptation during a month was shown to result in a growing activity of the enzymes both in the lymphocytes and in the myocardium. Hypoxia during a month and readaptation during the same period caused a monotonous decrease of the activity of dehydrogenases. The conducted analysis permitted to reveal a distinct correlation between the activity of dehydrogenases in the lymphocytes and in the myocardium. The authors emphasize the similarity of the changes in the activity of the enzymes in the lymphocytes and in the myocardium.


[Anticardiac antibodies, cross reacting with the membranes of streptococcus, in protracted rheumatic fever].

The anti-cardiac antibodies cross-reacting with the Streptococcal membranes were studied by the method of Zabriskie and co-authors in 162 patients with rheumatism in its active phase and in 181 control individuals. The anti-cardiac antibodies were found in over half of the rheumatic patients and far less frequently in the controls. At the same time in the majority of cases only those anti-cardiac antibodies that were found in the rheumatics possessed distinct cross-activity towards the A-streptococcal membranes. Most consistently were they found in those with a protracted course of the disease.


[Evolution of protracted septic endocarditis].

A study of 1000 cases of septic endocarditis served as a basis for an analysis of the natural history of the diseases (1939-1972): changes in its etiology, clinical course and therapy. The increasing frequency of hospital infection (endocarditis) is emphasized. The characteristics of Staphylococcal and fungal endocarditis are presented, those of the lesion developing on heart valve prostheses as well. The classification of septic endocarditis is analysed, the stages of its activeness are described (III, II, I) along with the clinical and laboratory signs. Schemes of etiotropic therapy are presented, as well as rational combinations of antibiotics. The role of surgery in the management of primary septic endocarditis is described, and the rationale of preventive employment of antibiotics is discussed.


[Pericarditis and heart tamponade in patients on regular hemodialysis].

Among 137 patients with terminal renal failure maintained on chronic haemodialysis, pericarditis was found in 37. In 11 cases it developed prior to the onset of haemodialysis therapy, and in 26 during various periods within the therapeutic course. In patients maintained on haemodialysis pericarditis is characterized by a protracted course, severe pain syndrome, ability to cause or intensify cardiac failure, to produce cardiac rhythm disorders. In 15 patients pericarditis was complicated by a massive effusion into the pericardiac cavity. In 3 of them the effusion gradually dissolved, 3 other ultimately developed subacute constrictive pericarditis, in the remaining 9 the effusion resulted in tamponade. Two patients died of cardiac tamponade, in the remaining 7 patients 12 transdiaphragmal pericardial punctures were performed. In 2 cases the latter caused severe complications. The discussion deals with the methods of treatment of pericarditis in patients on chronic haemodialysis, with the preventive measures against the effusion, and the means of its management.


[Cardiovascular pathology in dermatomyositis].

Among 110 patients with dermatomyositis cardiovascular pathology was found in 77, and only in 37 of them it was attributable to the underlying pathology. In all of these patients myocardial lesions were found, that manifested themselves most frequently by non-specific ECG changes. Cardiac insufficiency and arrhythmias were revealed less frequently, mainly during exacerbations of the pathological process. Only in one patient endocarditis was diagnosed, and in two others  elements of chronic cor pulmonale due to pneumonitis. In 18 patients signs of moderate myocardial dystrophy developed after a long-term therapy with corticosteroid hormones. A study of the central haemodynamics in 20 patients with dermatomyositis revealed a tendency towards a hyperkinetic state of the circulation in those patients who had the most sereve muscle syndrome. Angioscopy of the bulbar conjunctiva revealed the changes that persisted even during the remission period, achieved by means of active steroid therapy.


[State of the coronary circulation in patients with a chronic aneurysm of the heart].

Examination covered 56 patients with chronic post-infarction aneurysm of the heart. It included electro- and phonocariography, selective coronarography and ventriculography of the left heart. In the majority of these patients the affection started with myocardial infarction which gave rise to the development of the cardiac aneurysm. Coronarography disclosed a lesion of the left anterior descending artery in the form of an extended occlusion. Collateral coronary circulation was indefinable. Ventriculography of the left heart disclosed an aneurysm whose localization accorded with electrocardiographic indications. In the development of aneurysms of the heart the authors attach great importance to presence of collateral circulation at the instant of an acute lesion of the coronary artery.


[Results of 2-year study of morbidity of myocardial infarct (according to material of the myocardial infarction registry)].

The results of a two-year study conducted in accordance with the programme of the Myocardial Infarction Register in the Sokolniky district of Moscow with nearly 164,000 population are presented. The incidence of myocardial infarction in the 20-64 year age group comprises 2.87 and 3.08 among males and 1.52 and 1.44 among females, per 1,000 population for the 1st and 2nd years of the study respectively. The incidence of various clinical forms of myocardial infarction onset and of some complications developing in the acute phase of the disease was established. The typical variant of clinical manifestations is observed in 84.1% of the patients with the onset of myocardial infarction. The most frequently observed complication during the acute period of the disease (nearly in every 5th patient) is cardiac failure. Cardiogenic shock is observed only in 4.4-3.8% of the patients, aged under 64 years. Prior to the development of myocardial infarction 82.3% of the patients suffered angina pectoris, 55-62% arterial hypertension, 29-33% had survived another myocardial infarction earlier.


[Evaluation of the hypotensive effect and indications for the operation of nephropexy in patients with arterial hypertension combined with nephroptosis].

The results of the examination and nephropexy operation in 11 patients with arterial hypertension and nephroptosis are presented; a hypotensive effect was achieved in 5 of the operated patients; the follow-up period was up to 3 years. The recordings included the elevation of the arterial pressure in orthostasis, the changes in the urine sediment, the activity of plasma renin at rest and after 1-hour's orthostasis; excretory urography and the Seldinger abdominal aortography in a lying and upright position of the patient were conducted, as well as intraoperative biopsy of the renal tissue. Patients with a hypotensive effect exhibited a regular elevation of the arterial pressure in orthostasis, an increased plasma renin activity, congestive features in the descended kidney. The above symptoms permit to distinguish groups of patients with a hypotensive effect achieved after nephropexy, and those without effect. On the basis of the obtained results it was concluded that in some cases nephroptosis may be the cause of symptomatic arterial hypertension. In such cases it seems rational to recommend the nephropexy operation taking into account, when determining the indications for surgery, the degree of the orthostatic elevation of the arterial pressure and of the renin activity, and the symptoms of disorders in the renal evacuation function.


[Determination of the maximum speed of increase of pressure, the index and reserve of myocardial contractility as factors in hemodynamic studies of hypertension].

The authors' original non-invasive technique of determining the speed of pressure, elevation in the aorta, the index and reserve of myocardial contractility that reflects its contractile function was used in 80 persons (among them 25 normal individuals and 55 hypertonics). The main types of haemodynamic shifts noted in hypertension and its variants were described on the basis of simultaneous measurements performed by the above technique and by determinations of the cardiac output, speed of a pulse wave spreading and partial peripheral resistance. The suggested indices appeared to be the most sensitive ones permitting to detect the hypertensive type of the circulation of the initial stages of hypertensive disease.


[Surgical treatment of patent ductus arteriosus].

The experience gained with 1400 operations for patent ductus arteriosus performed at the Clinic of the Hospital Surgery of the Gorky Medical Institute during the period from October 1955 through 1973 is presented. The total post-operative lethality comprised 1.3 per cent, it amounting to 6 per cent with complicated patent ductus arteriosus, to 3 per cent among children of junior age and to 0.1 per cent in cases of uncomplicated defect. An analysis of operative and post-operative complications along with a study into remote results of the surgical intervention helped define indications for the closure of the duct in patients with pulmonary hypertension and septic endarteritis. They also showed the possibility of a single-stage correction of combined congenital heart defects. Indications have been worked out for the surgical treatment of patent ductus arteriosus in infants and procedures for the closure of the duct, depending upon its apatomic variants and concomitant complications.


[Levels of immunoreactive insulin and catecholamines in the blood plasma of patients with congestive heart failure].

The plasma level of the immunoreactive insulin and the blood level of sugar on an empty stomach and following carbohydrate provocation were determined in 31 patients with congestiva heart failure due to ischaemic heart disease. In 26 of them the plasma levels of adrenalin and noradrenalin were also studied. After 30-35 days of active therapy 15 patients were reexamined. The immunoreactive insulin plasma level was determined by the Hales and Randle technique, that of catecholamines-flowmetrically by the trioxyindol method after Vendsalu modified by E. Sh. Matlina. Carbohydrate metabolism disorders that manifested themselve in fasting hyperglycemia and in changing tolerance of glucose were noted in 13 of the 31 patients, examined. In the majority of patients with congestive heart failure insulin secretion was reduced both after fasting and after glucose administration. The improvement of the patients state in response to the employed therapy was accompanied by an increasing insulin secretion. One of the causes of the inhibition of insulin secretion in patients with congestive heart failure consisted in hypercatecholaminemia that was noted in most of the examined cases. The obtained data prove the necessity of a careful control of carbohydrate metabolism in patients with congestive heart failure and of a more active employment of insulin for their treatment.


[Level of metabolizable potassium in heart failure].

The amount of metabolizing potassium in the body was determined by means of K-42 dilution in 20 normal individuals and in 108 patients with different degrees of cardiac failure and various severity of the oedema syndrome. The amount of metabolizing potassium was found to decrease gradually along with the increase of cardiac insufficiency. Both the absolute amount of the metabolically active fraction of potassium was decreasing, and the content of this cation per 1 kg of body weight. The decrease of the amount of metabolizing potassium in cases of severe circulatory insufficiency did not depend on the severity of the oedema syndrome. With the improvement of the state of the patient and the decrease of congestive manifestations the level of metabolizing potassium tended to rise. Nevertheless, some patients demonstrated a reduction of the metabolically active fraction of potassium. And, vice versa, along with a deterioration of the patient's state and an increase of cardiac insufficiency and elevation of potassium content in the body was sometimes noted.


Spontaneous changes in weight, leg volume, renin, aldosterone and sex hormones in patients with cyclical oedema.

In four women with cyclical oedema related to the menstrual cycle, weight, leg volume, urinary excretion of sodium, aldosterone and oestrogens, plasma concentrations of progesterone, angiotensin II and plasma renin activity were measured at intervals during 4 weeks while they were taking a fixed sodium diet. In another patient, regular biphasic changes in weight and basal body temperature, disappearing after ovariectomy, were demonstrated. Changes in weight (varying between 3.5 and 5.5 kg) with corresponding changes in sodium balance were observed. In three patients, the maximum weight occurred in the second half, and in the other patient in the first half of the menstrual cycle. Plasms renin activity was in the normal range in all patients. It tended to rise when weight fell and vice versa. Aldosterone excretion behaved similarly and seems to be related to plasma progesterone in three patients. Orthostatic increase in leg volume did not significantly correlate with change in early morning weight. Thus, renin, aldosterone and orthostatic pooling of plasma fluid did not seem to be of primary importance in the pathogenesis of oedema in these patients. Oestrogen excretion in the luteal phase of the cycle was abnormally low in two patients; both had premenstrual oedema. In none of the patients could sodium retention be explained by excessive oestrogen and/or diminished progesterone production.


[Clinical value of His bundle electrography (author's transl)].

Methodical problems, indication and clinical implication of His bundle electrography are discussed. In 200 successive patients undergoing His bundle electrography and atrial stimulation the indication was as follows: Intraventricular conduction defects in 24%, A-V block in 21%, sick sinus syndrome in 20%, preexcitation in 17%, and complex arrhythmias in the remaining cases. In 38% of the patients did the HBE prove to be of help by providing information not available after analysis of the surface ECG. In 22% this technique contributed essentially to the management of these patients. In spite of dificiencies of our knowledge of the basic mechanisms, specific therapy, and prognosis of various arrhythmias His bundle electrography is clinically useful in selected patients. Therefore, this method has become a routinely used clinical tool.


[Dosage and elimination of Dextran 40 in patients on hemodialysis (author's transl)].

In 24 patients on regular hemodialysis the serum levels and the half-life of dextran 40 were determined after single or repeated infusion of dextran 40 (Rheomacrodex¿). One group of hemodialysis trainees had a dextran 40 half-life of 2237 +/- 447 min. In contrast, a second group, consisting of hospital dialysis patients, had a dextran 40 half-life of 4283 +/- 510 min, whereas patients with normal renal function had a half-life of 573 +/- 183 min. The difference in dextran half-life between the two groups of hemodialysis patients may be explained by the better residual renal function of our hemodialysis trainees. During hemodialysis no change in serum dextran levels could be observed. Intermitten hemodialysis, also, had no influence on the exponential elimination of dextran over a period of 6.25 days. Since hemodialysis by itself has no effect upon dextran elimination, the dosage fo dextran 40 has to be adjucted to the prolonged elimination time only, disregarding dialysis. After the fourth infusion of 50 g dextran 40 (twice a week 500 ml of 10% dextran 40) serum dextran levels exceeding 50 g/l and cutaneous bleeding were observed. To avoid these complications an initial saturation dose is suggested, followed by a maintenance dose adjusted to the impaired renal function.


[Cardiac effects and glycoside concentrations in serum and urine after oral administration of beta-methy-digoxin to healthy individuals (author's transl)].

Six healthy individuals were digitalized orally with beta-methyl-digoxin. The serum glycoside concentration, determined radioimmunologically at the end of the digitalization period was 1.2 +/- 0.22 ng/ml. At this period of time renal excretion attained 55.9% of the daily administered oral dose. The calculated renal clearance of beta-methyl-digoxin was 63 +/- 8.1 ml/min e. g. 57.5 +/- 8.3 ml/min/1.73 m2. After discontinuation of the glycoside the serum half life was 54 h. During the digitalization period the cardiac glycoside effects could be measured by ECG changes, especially a shortening of the QT interval as well as a shortening of the left ventricular ejection time and the pre ejection period, corrected for the heart rate.


Effects of synthetic somatostatin on endotoxin-induced changes of growth hormone, cortisol and insulin in plasma, blood sugar and blood leukocytes in man.

In normal man synthetic somatostatin inhibits the growth hormone response to intravenous administration of endotoxin (Piromen), but exerts no influence on cortisol plasma levels. Endotoxin-induced leukocytosis in blood is significantly reduced by somatostatin. Plasma levels of insulin and the blood sugar in man receiving endotoxin are firstly reduced in a significant manner and then increasing to normal values during somatostatin infusion.


Half-life plasma following repetitive application of beta-acetyl digoxin in man.

The aim of this study was to determine the half-life of beta-acetyl digoxin in plasma after cessation of its continous oral application. 18 healthy male volunteers received 0.4 mg p.o. of beta-acetyl digoxin daily for a period of 14 days. Plasma glycoside concentrations were measured up to 108 hours after the last application utilizing a 86Rb-erythrocyte assay. Mean plasma digoxin concentration 12 hours after the alst dose was -x=1.05 ng/ml, sx=0.301. Mean half-life in plasma was 55.8 hours (sx=21.7). This corresponds to a mean daily elimination rate of abour 25.8%. These results are in good agreement with the 20% loss of effect on the heart as reported in the literature.


[Effect of selective proximal vagotomy with and without pyloroplasty upon basal and food stimulated serum immunoreactive gastrin in patients with duodenal ulcer. (author's transl)].

The effect of selective proximal vagotomy (SpV) with (12 cases) and without (5 cases) pyloroplasty upon basal and food stimulated serum immunoreactive gastrin (IRG) was studied in duodenal ulcer patients. Following SpV, fasting serum IRG increased in all subjects; the increase was more pronounced in subjects whose postoperative insulin tests were negative. Postoperatively, the mean integrated IRG output over 2 hrs in response to a meal was significantly higher than the preoperative mean value in the 17 patients. Pyloroplasty had no effect upon the IRG response following a test meal.


[Simplified rapid determination of plasma digoxin. Methods and clinical evaluation].

The introduction of the Gamma Coat 125I-Digoxin Radioimmunoassay has simplified the digoxin determination to an extent that it may be used even in general hospitals with an intensive care unit. The total time for a stat determination has been reduced to 70 min. The coefficient of variation of the digoxin determination at low levels (less than 0.8 ng/ml) was less than 15% for simultaneous and repeated measurements even when using one of the inexpensive nuclear counting systems. At high levels (greater than 2.5 ng/ml) the coefficient of variation showed to be less than 6%. Hemolysis, low albumine concentration and other than digoxin-bound isotopes in the blood samples did not cause methologic problems. Provided that resorption and elimination kinetics of the different digoxin preparations were taken into account, digoxin levels of more than 2 ng/ml as measured by the Gamma Coat method in patients with normal renal function plasma were usually associated with clinical signs of overdosage; therapeutic concentrations were mostly higher than 1.2 ng/ml. The incidence of digitalis toxicity with high digoxin levels was lower in uremic than in normal patients. According to preliminary observations in dialysis patients this increase in tolerance to digitalis, may be a consequence of hyperkalemia and renal acidosis. Erroneously high digoxin concentrations were found in patients up to 2 hrs after injection of high doses of spironolactone (400-1000 mg) due to cross reaction. Therapeutic concentrations of digitoxin (10-25 ng/ml) caused only subtherapeutic digoxin concentrations of 0.4-0.9 ng/ml.


[Plasma aldosterone and plasma renin activity in patients with essential and renal hypertension under acute stimulation with saline depletion and acute suppression with saline infusion].

Plasma aldosterone, plasma renin activity, sodium and potassium in the plasma and the urine were determinated under acute stimulation with saline-depletion (furosemide) and under acute suppression with saline infusion in 40 patients with primary hypertension stage I, 19 patients with primary hypertension stages II and III, and 11 patients with renal hypertension (chronic glomerulonephritis and chronic pyelonephritis). The majority of the patients with primary hypertension stage I showed a good stimulation of the plasma aldosterone and the plasma renin activity under acute salt depletion. Three out of the 40 patients with primary hypertension stage I, and 13 of the 19 patients with primary hypertension stages II and III did not show any stimulation of the renin secretion ("low renin hypertension"). In all these patients the plasma aldosterone stimulation remained intact. With infusion of saline all the groups showed suppression of the plasma aldosterone and the plasma renin activity. A good stimulation of the plasma renin activity, demonstrates that in our experiments the renin-angiotensin system cannot be responsible for the increase in aldosterone secretion under salt depletion. Most likely the increase of the plasma aldosterone, in spite of the fixed renin activity, is stimulated by the sodium depletion due to diuretics. In all patients with primary hypertension we did not find an inadequate reaction of the aldosterone secretion under saline infusion. The patients with renal hypertension showed a minimal stimulation and suppression of the plasma renin activity. The plasma aldosterone secretion increased only slightly under sodium depletion and the decrease under saline infusion was statistically not significant. Thus we conclude that these patients show an inadequate reaction of the plasma aldosterone and renin secretion under salt infusion and depletion.


[Investigations concerning the fixation of hepatitis B-antigen (HBAg) on peripheral lymphocytes and isolated hepatocytes in patients with inflammatory liver diseases. (author's transl)].

The fixation of HBAg on lymphocytes was investigated in 127 patients with various inflammatory liver diseases. The fixation of HBAg on lymphocytes and isolated hepatocytes as well as the fixation of IgG on isolated hepatocytes were studied in 60 cases. Membrane-fixed HBAg could in no case be demonstrated on isolated hepatocytes whether these cells were derived from patients with or without HBAg in the serum. HBAg on hymphocytes was detectable in most cases of acute hepatitis during the phase when HBAg disappeared from the serum. HBAg on lymphocytes was detectable in most cases of acute hepatitis during the phase when HBAg disappeared from the serum (time of immunoelimination). Membrane-fixed IgG could be mainly demonstrated in HBAg positive acute hepatitis with a protracted course or in HBAg-positive active chronic hepatitis and signs of inflammatory activity. The results obtained for HBAg-carriers indicate (a) an immunological tolerance against HBAg, (b) a persistance of the virus infection in liver cells, and (c) an antibody-mediated cyto- and histotoxicity as a pathogenetic principle for the course of certain chronic liver diseases. The antigenic determinant of the membrane-fixed antibody is not known until now.


The role of testosterone in the feedback control of male FSH and LH secretion.

Intramuscular administration of 250 mg testosterone oenanthate per week over a period of 21 weeks treatment rapidly and sustainedly suppressed serum LH as well as FSH levels in seven normal males, while serum testosterone rose by a factor of approximately two. These together with other data provide increasing evidence for a feedback control of FSH secretion by gonadal steroids in the male in addition to the already described but as yet undefined tubular testicular factor.


[Efficacy of ultrasonography in pancreatic disorders compared to endoscopic retrograde pancreaticography (author's transl)].

To evaluate the diagnostic efficacy of ultrasonography in pancreatic disorders the results were compared with endoscopic retrograde pancreaticography in 140 II resection-retrograde cannulation of Vater's papilla was unsuccessful, examination of the pancreas was not possible in 20 patients with ultrasonography because of meteorism of severe adipositas. In 15 subjects the sonographic findings were equivocal. Out of 105 ultrasonic findings three were false-negative and 5 false-positive, whereas retrograde Wirsungography resulted in 9 false-negative and 2 false-positive interpretations. In 50 out of 67 cases of pancreatic disorders diagnosed by ultrasonography a further differentiation between malignant tumours and benign pseudotumours (pancreatitis or cyst) was possible. With respect to the diagnosis of pancreatic cysts ultrasonography was superior by 23 of 27 to retrograde pancreaticography (12 out of 27) since many cysts do not communicate with the ductal system. In comparison with the endoscopic method the risklessness and the low expenses have to be stressed. Both methods supplement each other, so that a high diagnostic accuracy is reached (more than 95 per cent).


[Comparison of digitoxin bioavailability from tablets and elixir during maintenance therapy (author's transl)].

The bioavalability of digoxin tablets and solution has been studied during maintenance therapy in a cross over study.  Each preparation was given over a period of at least 7 days to patients with compensated congestive heart failure.  Urine concentrations and plasma levels were analysed for digitoxin.  There was no significant difference between the two preparations.  Determination of steady state serum concentrations and urinary excretion during maintenance therapy as an index of bioavalability are more cumbersome than a single dose study.  From a pharmacokinetic point of view however, analyses of steady-state conditions are preferable to a single dose study.  In addition, steady state of drug input and output resembles the usual digitalis therapy.


Diphenylhydantoin: correlation between protein binding and albumin concentration.

The unbound fraction of diphenylhydantoin is inversely correlated with the patient's serum albumin concentration and can be accurately estimated graphically without binding analyses.  The data for this relationship was obtained from a study in which we observed that the unbound fraction of diphenylhydantoin was two times higher in patients with the nephrotic syndrome.  However, in these patients it was not necessary to diminish the dosage since the absolute concentration of unbond drug was unchanged due to a compensatory increase in the apparent volume of distribution and plasma clearance.


[Carcinofetal antigens.  III. Further carcinofetal antigens (author's transl)].

The occurrance and significance of important carcinofetal antigens other than AFP and CEA are reported.  These included the alpha 2 H-protein which is produced in the liver and increases in serum of patients with various tumors, the fetal sulphoglycoprotein antigen FSA from the gastric juice of patients with gastric cancer, the carcinoplacental alkaline phosphatase (REGAN-isoenzyme)which is found in the serum of patients suffering from e.g. bronchogenic, mammary, urogenital and gastrointestinal carcinomas, the beta-S-fetoprotein which is most likely to be identical with C-reactive protein, gamma-fetoprotein, the carcinofetal antigen in glial tumors (CFGA); ectopic production of placental hormones like human gonadotropin, placental lactogen, plasminogen-activators; leukemia-associated antigens.  Furthermore, some other less known carcinofetal antigens are mentioned.


[Comparative characteristics of poly- and monomeric protein nutrition in relation to space flight].

The use of pure protein mono- and polymers for human nutrition was studied in a 45-day experiment in which 12 test subjects took part. The first group of 6 persons were given casein (14.8 g nitrogen per day) and the second group--an equivalent mixture made of crystalline L-amino acids. The first group showed no abnormalities in the physiological and biochemical functions. The second group exhibited marked changes in the body: weight losses, negative nitrogen balance, increase of the ammonia concentration in the urine and exhaled air. It appears that amino acid mixtures can be included into the human nutrition only after extensive studies.


[Model of gas transport in periodically ventilated lungs].

By mathematical modelling the effect of discrete pulmonary ventilation, i. e. alternation of inhalations and exhalations, on the gas transport in the lungs was studied. The qualitative analysis of the system of differential equations describing changes in the air composition in the alveoli during the breathing cycle demonstrated that at least twice per each respiratory cycle the alveolar air had the ideal composition predicted by the normal continuously ventilated model of the lungs. This result pointed to the sum total of possible values of the air composition in different sites of nonhomogenously functioning lungs. This lung model took into consideration the effect of the volume concentration of the inert gas in the breathing mixture and high solubility of CO2 in the blood and pulmonary tissues on the pulmonary gas exchange.


[Changes in physiological indices in albino rats exposed to accleration for 24 hours].

The physiological effect of prolonged accelerations of 2 and 4 g applied longitudinally and transversely to the long axis of the body of white rats was studied. The animals exposed to accelerations for 24 hours showed a decrease in the heart rate, respiration rate, rectal temperature, pO2, and pCO2 in the peripheral tissues.


[Autonomic reactions in rabbits exposed to a constant magnetic field].

Chronic experiments on rabbits have shown that their exposure to a constant magnetic field of 4500 oersted for 3 hours causes a transient hypotension, a decrease in the respiratory rate and a trend for bradycardia. Immediately after the exposure the pressor reaction and bradycardia level decrease and by the end of the first day they increase. At this time the respiratory rate increases in response to the administration of epinephrine, acethylcholine or stimulation of the midbrain reticular formation. The exposure does not decrease the compensatory possibilities of the cardiovascular and respiratory systems. This follows from their reactions to accelerations of 6 and 10 g.


[Use of elongated and shortened days in space flights].

On the basis of the experimental findings and the literature data it is concluded that a 24-hour day should be recommended for space missions. It is assumed that in future prolonged or shortened days may be used. This is confirmed by the hypothesis that the information-energy cost of the diurnal cyle is constant.


[Hypobaric nitrogen-oxygen atmosphere as a method of preventing altitude decompression sickness].

It has been shown experimentally that the development of altitude decompression disease at 250 and 180 mm Hg can be prevented by preliminary desaturation in the nitrogen-oxygen hypobaric atmosphere (60% N2 and 40% O2 at 550 mm Hg). This has been demonstrated in 38 experiments on 21 test subjects. The use of this atmosphere in space cabin prevents the development of decompression disease upon a decrease of the cabin pressure to 250 mm Hg and upon extravehicular activity in a space suit with 180--200 mm Hg.


[Theoretical aspects of developing a system of medical control in space flights].

The paper presents theortical approaches to the medical control system in prolonged space flights. It classifies the most probable states in long-term weightlessness. The main symptoms of these states are described. On the basis of this classification methods and parameters to be used in diagnosis of symptoms that may occur in space flights are discussed.