[Relationship between the pathomorphological characteristics of the lungs and surfactant properties in some forms of chronic pneumonia]. The minimum surface tension (STmin) and the content of total lipids (TL) and phospholipids (PL) in a surfactant obtained by differential centrifugation of extracts from 56 fragments of lungs resected from 48 patients with segmentary suppurations and bronchiectasia were correlated with the results of morphological and histochemical studies. The controls consisted of 5 lungs from the subjects dying of accidental causes. Areas of interstitial pneumosclerosis, atelectasis and carnification were found to have a high STmin and to contain less than 1 mg of PL per 1 g of the lung tissue, whereas foci of emphysema had a lower STmin and a higher content of PL. These parameters are inversely related. Possible causes of the change of the surfactant condition in chronic pneumonia and practical importance of its examination in resected lungs for a diverse evaluation of the pathological process and the effectiveness of preoperational therapy are discussed.


Reexamination of the acoustic method in measurement of Eustachian tube function. In order to assess the reliability of the acoustic method in examination of Eustachian tube function, 30 subjects with normal, obstructive or patent tubes were examined twice, by the acoustic method, and by the aerodynamic method which we have developed. The reliability of the aerodynamic method has been confirmed by repeated clinical examinations. 60% of the results of the acoustic method were found to disagree with both the results of the aerodynamic method and the clinical findings of the tested ears. One cause of this disagreement was shown to be the influence of motion accompanying deglutition upon the sound transmission.


Organ culture of the postnatal mouse Crista ampullaris. Part I. The 2 day post partum mouse Crista ampullaris was cultured "in vitro" for 7 days. The differentiation into secretory and sensory areas was preserved. The ultrastructure of the dark cells of the secretory region was well maintained. The hair cell morphologically was considerably changed though the hair cells themselves survived 7 days in culture.


[Tympanoplasty with human dura mater preserved in cialit (author's transl)]. In 26 cases allogenetic human dura mater, conserved in CialitTM 1:5000, was used to close perforations of the eardrum instead of commonly used autogenetic fascia of the temporal muscle. In preceding animal studies, it had been found that "Cialit dura" acts as guideline and stimulates the development of new host connective tissue. In 25 human ear drums the perforations healed up without any problems. The healing process took times of up to 8 weeks. Only in one case a new perforation was found. The moderate flexibility of "Cialit dura" proved as a special advantage during the surgery procedure. Human dura is easily to acquire and its conservation is simple and cheep. Therefore it can serve as a grafting material for tympanoplasty available at any time and in any size. For very large transplants and a lack of postoperative treatment the prolonged healing period could be of some disadvantage. For normal sized transplants, however, there seems not to be a difference in healing time between the commonly used fascia and the "Cialit dura".


A new one-stage surgical technique for postlaryngectomy speech. A new one-stage surgical technique for the postlaryngectomy speech applied to the 17 patients and its results are described herein. The essential part of this technique consists of the construction of a tracheo-esophageal shunt using only the remainder of the trachea obtained at the time of laryngectomy to reestablish an air communication between the trachea and the gullet. Fourteen patients of the 17 patients thus operated upon developed conversational abilities equivalent to the normal subject, except that they use a finger during the speech for the occlusion of the tracheal opening. This technique can be applied to almost all candidates for total laryngectomy with or without neck dissection. The initial speech was developed in 25 days after operation in average. The inflow of the salivas and/or fluids into trachea is not problematic in these patients. It has been well known that an air communication reestablished between the natural air way and the gullet could reproduce a vocal function after total laryngectomy [5]. Despite very few surgical techniques for this purpose have been described and applied clinically, although a tremendous effort has been made for the complete removal of the malignancy and the avoidance of recurrence up to the present [1--4, 6]. A new surgical method for achieving a tracheo-esophageal shunt for the postoperative vocal function is described herein.


[Narrow nystagmus writing and hypoxemia of the central vestibular system (author's transl)]. To explain the origin of the narrow nystagmus writing (petite écriture), selected patients with hypoxemia were examined using the pendular rotating test and ENG. Bloodgas analysis was used to determine pO2 reduction. The decreased oxygen saturation was corresponding to the decreased amplitude of nystagmus. In a second experiment with alert rabbits the inspired gas mixture was altered to obtain hypoxia (8% O2 + 92% N2, controlled with bloodgas analysis). A significant reduction from the normal nystagmus reaction was observed. This reduction in the amplitude (about 50%) is immediately reversible by giving oxygen. These experiments were repeated with each animal several times, the results being reproductible. There is a significant decrease in nystagmusamplitude through the influence of hypoxia.


Ear morphology in Treacher Collins', Apert's, and Crouzon's syndromes. Size, proportions, level, inclination and shape of the ears were assessed by anthrompometric methods in eight patients with Treacher Collins' syndrome, eleven with Apert's, and 25 with Crouzon's syndrome. The ears were most severely damaged in Treacher Collins' syndrome, in which they were microtic or disproportionally long; many were low-set and with great inclination. All patients with Apert's syndrome had low-set ears and a tendency to disproportion, with widening and small inclination of the longitudinal axis. The ears were least affected in Crouzon's syndrome; in two-thirds of the patients there were mild growth variations leading to disproportion in width (wide ears), or low-set ears, or both.


Vertical location of the ear, assessed by the Leiber test, in healthy North American Caucasians 6--19 years of age. A method of assessing the level of the ears, slightly modified from that devised by Leiber (1972), and the instrument developed for the measurements, are described. In a study of 1312 healthy North American Caucasians of both sexes aged 6--19 years, dystopic ears were found in 15 (1.2%). The ears were low-set in 13 (5 bilateral and 8 unilateral), in more males (8) than females (5), and were high-set in 2 (bilateral in a girl and unilateral in a boy). The level of normally located ears changed with age, from low-normal location in early school age to middle-normal in young adulthood. Almost 10% of "normally" located ears were situated asymmetrically, but these asymmetries could not be detected visually.


[Meproscillarin, a new semisynthetic cardiac glycoside/chemistry and physical properties (author's transl)]. 14-Hydroxy-3beta-[4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin) is a new semisynthetic glycoside for the therapy of cardiac insufficiency. The preparation from proscillaridin and the chemical and physical properties are described.


[Labelling meproscillarin with tritium at the C-19 position (author's transl)]. Labelling of 14-hydroxy-3beta-[4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) by introduction of dueterium and tritium at the metabolically stable C-19 position is described.


[Studies on the disposition of meproscillarin in rat and dog (author's transl)]. The disposition of 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) formed by methylation of proscillaridin was tested in rats and dogs. Meproscillarin is better absorbed than proscillaridin. The drug is primarily eliminated via the bile. After oral administration 6% of the dose were excreted with urine by the rat and 3% by the dog. The main metabolite in the bile was shown to be a glucuronide of meproscillarin.


[On the development of an oral preparation of meproscillarin (author's transl)]. Analytical methods of determination, investigations of stability and the behaviour of the substance in artificial gastric and intestinal fluids are the bases for the formulation of an oral preparation of 14-hydroxy-3beta-[4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift). The problems of developing a stable form, the maintenance of uniform content and the bioavailability are discussed.


[Metabolism of meproscillarin in man (author's transl)]. The investigations on the metabolism of 14-Hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) were performed in 5 healthy test persons as well as in 4 patients with biliary fistula, applying a single oral dose of 0.5 mg of 3H-meproscillarin. The elimination half-life of total plasma radioactivity was about 51 h in the test persons, and 18 and 30 h in the patients whose bile was drawn off via a T-drain. The test persons excreted about 20% of total radioactivity renally and about 56% with the faeces. The patients excreted between 29% and 89% of the radioactive dose applied with the bile, the major part being eliminated already after 24 h. Up to 3% was excreted with the faeces. Renal excretion varied between 6% and 22%. Total radioactivity in plasma, bile, urine and faeces was separated into chloroform-soluble and chloroform-insoluble fractions, which were further differentiated by thin-layer chromatography. Whereas in plasma, bile and urine mainly chloroform-insoluble metabolites of meproscillarin were present, the chloroform-soluble fraction in the faeces represented the major portion, also containing primarily meproscillarin. The results are discussed.


[Effect of meproscillarin on left ventricular hemodynamics (author's transl)]. In 10 patients with angiographically proven coronary artery disease we investigated the influence of the glycoside 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) on left ventricular performance with invasive methods. After a single i.v. bolus injection a decrease in left ventricular end-diastolic pressure associated with an increase of the maximum rate of pressure rise (dp/dtmax) and left ventricular pressure (LVP) was observed. These changes were not accompanied by significant alterations of the heart rate during an observation period of 60 min.


[Preliminary hemodynamic studies on the activity of meproscillarin (author's transl)]. In 10 patients with arterial hypertension and left heart failure the hemodynamic effect of 14-hydroxy-3-beta-[4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (Ky 18, meproscillarin, Clift) was compared with placebo in a double-blind study. 15 min after oral administration of meproscillarin there was an increase of cardiac output and stroke volume by up to 25%. Heart rate, arterial blood pressure and left ventricular filling pressure remained unchanged.


[The influence of meproscillarin on human left ventricular function (author's transl)]. Left ventricular (LV) function was assessed by echocardiography in 11 cardiac patients before and after treatment with 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)-oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift). This drug was given during 7 days in a dose of 4 X 0.25 mg/d. During a placebo period of 7 days the LV function parameters percent systolic shortening of the transverse LV diameter and mean velocity of circumferential fiber shortening did not change significantly but increased significantly (P less than 0.001) after meproscillarine. Heart rate and end-diastolic LV diameter remained unchanged throughout the study. It is concluded that peroral meproscillarin induced a true increase of LV inotropic state.


[Clinical study of meproscillarin rates of inactivation and persistence, bioavailability and maintenance dose]. With a rate of inactivation of about 40% and a bioavailability of about 70% corresponding approximately to that of digoxin 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) is--according to our results--a new therapeutic possibility for cardiac decompensated patients, especially in the presence of renal failure. The number of side effects was low. Occasionally diarrhoea occurred which, however, only in a few cases required treatment or discontinuance of therapy.


[On the possible meproscillarin accumulation in patients with impaired renal function (author's transl)]. 26 patients with impaired renal function and 7 healthy subjects received an oral dose of 0.5 mg 14-Hydroxy-3-beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) per day for 2 weeks. Plasma levels of meproscillarin were measured during and after this period by means of the 86Rb-erythrocyte method. No statistically significant differences were found between the 2 groups. The results are consistent with extrarenal elimination of the substance. Contrary to digoxin, e.g., dose reduction is unnecessary in chronic renal failure. Mild gastrointestinal symtpoms were the only side effects seen in 6 patients.


[Elimination rate of meproscillarin following repeated application in patients with reduced renal function (author's transl)]. It was to be investigated whether the elimination rate of 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) is influenced by the renal function after discontinuance of long-term application. A group of 9 patients with renal insufficiency of varying extent associated with heart failure received 0.75 mg of meproscillarin per day over a period of 14 days. The plasma levels of the glycoside were measured by means of the 86rubidium erythrocyte assay up to 60 h after the last dose. After discontinuance of the glycoside the mean plasma half-life was 45.8 (S.-X = 6 h), a value corresponding to the results obtained in healthy test persons (49.3 h). Thus it could be demonstrated that the rapid elimination rate (and thereby the rate of inactivation) of meproscillarin is not influenced by renal function even after discontinuance of long-term application.


[Elimination of meproscillarin by hemoperfusion (author's transl)]. Starting from toxic concentrations of the new scilla glycoside 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)-oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) 5 in vitro hemoperfusions with the hemoperfusion system Haemocol are described. The test showed that meproscillarin may be rapidly eliminated from the blood by adsorption to activated charcoal (hemoperfusion). The text provides basic information for possible intoxications.


Effect of maternal dexamethasone therapy on the levels of oestrogens, progesterone and chorionic gonadotrophin in amniotic fluid and maternal serum. Ten women were given dexamethasone intramuscularly in order to accelerate fetal lung maturation. Amniotic fluid and maternal serum were assayed for oestrone, oestradiol-17beta, oestriol, progesterone and chorionic gonadotrophin by specific radioimmunoassays before and after the treatment. No hormonal changes were observed in amniotic fluid. The serum levels of oestrogens 2 to 5 days after treatment were not significantly different from those before treatment, indicating that the previously reported suppression of oestrogen production by glucocorticoids disappears rapidly after treatment stops.


The effects of the thermal prephase transition and salts on the coagulation and flocculation of phosphatidylcholine bilayer vesicles. Absorbance measurements of sonicated dipalmitoyl phosphatidylcholine vesicles reveal two aggregation processes: flocculation and coagulation. Flocculation is only observed for samples in monovalent cationic salt solutions or in salt-free suspensions. This process is abolished in the presence of di- or trivalent cations. It is also found to be strongly temperature dependent, occurring only below the thermal prephase transition of the lipid. Dispersal of the flocculates is rapid but they re-form at a rate dictated by the hysteresis in the prephase transition. In contrast, coagulation is slow. The extent of coagulation does not seem to be strongly dependent on the temperature, the nature of the electrolyte or its concentration. The relation of the coagulated state to vesicle-vesicle fusion is briefly discussed.


Survival of nodular versus diffuse pattern lymphocytic poorly differentiated lymphoma. Response and survival were analyzed in 97 patients with NLPD (Nodular Lymphocytic Poorly Differentiated Lymphoma) and 77 with DLPD (Diffuse Lymphocytic Poorly Differentiated) treated by intensive versus moderate chemotherapy regimens. The complete and overall response rate in NLPD of 47% and 81% was significantly superior to 25% and 59% obtained in DLPD. The estimated two year survival of 83% in NLPD was also significantly superior to 47% two year survivorship of DLPD (p less than .001). The chemotherapy responsiveness had a significantly favorable effect on DLPD survivorship with two year survivals of 84% for CR, 58% for PR and 17% for PD. In NLPD the effect of chemotherapy responsiveness on survival was less striking (CR 91%, PR 85%,  and PD 72% surviving two years). The data, in our opinion, confirm the rationale for the use of aggressive multiple agent chemotherapy regimens in DLPD where achievement of compelte response appears to be the single most important factor in improving survivorship. On the other hand NLPD, with excellent survival rates which appear to be only partially dependent on chemotherapy responsiveness might serve as an ideal model for moderate intensity or single agent chemotherapy trials.


Chemotherapy (cyclophosphamide, vincristine, and prednisone) versus radiotherapy (total body irradiation) for stage III-IV poorly differentiated lymphocytic lymphoma. Seventy-two patients with stage III-IV malignant lymphoma of the poorly differentiated lymphocytic (PDL) type were randomly assigned to initial chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or to radiotherapy with total body irradiation (TBI). The response and survival rates were similar for CVP and TBI in patients with nodular PDL, with 66% and 67%, respectively, surviving at 7 years. Induction treatment with TBI yielded better response and early survival than CVP for patients with diffuse PDL but a survival advantage did not exist at 5 years, the survival rate being 28% and 25%, respectively.  TBI was more easily tolerated than CVP as initial therapy, 19 (51%) of the 37 CVP patients had a complication which required hospitalization during the first six cycles as contrasted to only one of 35 patients receiving TBI who required hospitalization. Most chemotherapy complications were infectious in nature, secondary to relatively severe granulocytopenia, and one patient died from Candida sepsis following the first cycle of CVP. Late complications consisted of two TBI patients who developed a myeloproliferative disorder and two CVP patients who experienced persistent disabling neurotoxic reactions. Durable remissions were not achieved with significant frequency using either form of treatment, indicating a need to evaluate new therapeutic approaches for the management of PDL lymphoma.


Cutaneous tuberculosis and malignancy.

Cutaneous tuberculosis and malignancy. This is a report of three cases of associated tuberculous and neoplastic processes. The first is a case of lymphosarcoma complicated by cutaneous tuberculosis. The remaining two are cases of cutaneous tuberculosis complicated by squamouse cell carcinoma. Due to clinical similarity, the diagnosis of the secondary process in these cases was evoked by its failure to respond to treatment of the primary disease.


Metabolic effects of some antibilharzial drugs. Studies on the inhibitory action of "bilharcid" on succinate oxidation in normal rat liver. THE INHIBITION of succinate oxidation by Piperazine diantimonyl tartarate (Bilharcid) could be in part attributed to accumulation of oxaloacetate. This is discussed with reference to the effect of ATP, glutamate and cysteine on the reversal of the inhibitory action, of the drug on succinate oxidation.


Amniotic fluid proteins and lipids in normal and high-risk pregnancies and their relation to foetal outcome. Amniotic fluid total lipids (T.L.), lipid phosphorus (L.Ph.), phospholipids (Ph.L.), total cholesterol (T.Ch.), total proteins (T.P.) and inorganic phosphorus (I.Ph) were determined in a number of high risk pregnancies and compared to parallel data obtained for full term normal pregnancies. Amniotic fluid T.L., L.Ph., Ph.L. and T.Ch. were significantly decreased in diabetic and toxaemic cases. The decrement in L.Ph. and Ph.L. was more pronounced in diabetic and toxaemic mothers who delivered either still-births or neonates suffering from RDS or in cases of intrapartum death. The L.Ph. and Ph.L. were increased in case of toxaemic mothers who delivered living neonates with no RDS. In spite of the increase in T.Ch. in the same cases; the ratio of T.Ch to T.L. was constant except in cases with prolonged intrauterine foetal death where it was increased.


Molecular arrangement of cervical mucus: a reevaluation based on laser light-scattering spectroscopy. Evidence obtained from laser light-scattering spectroscopy suggests that the molecular arrangement of cow estrous cervical mucus is an ensemble of entangled random-coiled macromolecules rather than a cross-linked macromolecular network, the model heretofore widely accepted. This new model can account for the following phenomena: (1) The viscoelastic properties of the estrous mucus and human mid-cycle cervical mucus are the result of the way in which the glycoproteins are entangled. Variations of these properties during the reproductive cycle may simply be due to changes in the water content of the cervical mucus. (2) Penetration of spermatozoa in mucus may be entirely mechanical without involving any kind of enzymatic lysis of cross-links (this is supported by changes in the pattern of spermatozoa flagellation during sperm penetration of cervical mucus as shown in motion picture films). (3) The orientation of spermatozoa in the cervical muscus need not be due to the presence of 'channels' between micelles but simply to an artifact, the stretching or flow of the mucus, which orients the entangled macromolecules and thus facilitates the penetration of spermatozoa in an axis parallel to them.


Attempted induction of granulosa cell tumor in Balb-C mice by gonadotropin administration. An attempt of granulosa cell tumor (GCT) induction by prolonged administration of exogenous pregnant mare's serum gonadotropin (PMSG) to young, mature, and middle-aged Balb-C mice resulted mainly in stromal luteal cell proliferation. 48.9% of young mice, 64.5% of mature mice and 65% of middle-aged mice developed luteal cell proliferation. This effect seemed to be dependent on duration of treatment, mainly in young mice. Young mice injected for less than 6 months developed significantly less luteal cell proliferation than those injected for more than 6 months. Only 1 GCT was found. This study seems to support the contention that besides gonadotropin stimulation, other factors may be involved in GCT development. A large number of PMSG-injected mice developed generalized lymphosarcoma, the mechanism of which remains unknown.


Organizational leaders grapple with nutrition education issues. The leaders of four food service organizations met recently in Chicago to exchange information about nutrition education. Highlights of that conference are described herein, including a presentation on the AHA's Center for Health Promotion.


[The Netherton syndrome with alopecia and prolinuria]. A six month old boy under observation for over two years developed an ichthyosiform erythroderma with alopecia, which was diagnosed as Netherton syndrome. Histologic examination of the hair roots showed trichorrhexis invaginata (bamboo hair), trichorrhexis invaginata torta and pili torti. Prolinuria was detected. Local therapy with corticosteroids was without any effect. These symptoms can be attributed to aminoaciduria (prolinuria).


Milk drinking by the elderly of three races. The three objectives of this study were to determine: (a) If milk was acceptable for multi-racial groups of elderly people, some of whom had previously been described as lactose intolerant, (b) the frequency of milk rejection attributed to symptoms of lactose intolerance, and (c) the importance of offering different types of milk. The study was carried out on 347 elderly citizens participating in the Title VII Nutrition Program for the Elderly in Harris County, Texas. Eighty-five per cent of the Mexican-Americans, 93.5 per cent of the blacks, and 94 per cent of the Anglos surveyed reported drinking the milk served with their meal. Only 6.6 per cent of the Mexican-Americans, 1.4 per cent of the blacks, and 2.5 per cent of the Anglos did not consume the milk because of symptoms that might be related to low levels of intestinal lactase. It was concluded that milk could and should be served to multi-racial groups of elderly people. Offering a choice of milk type appeared to be important for acceptance. Twenty-two per cent of the blacks, 4 per cent of the Mexican-Americans, and 16 per cent of the Anglos always preferred buttermilk.


Temporal and spatial patterns of the synthesis of tissue-specific polypeptides in the preimplantation mouse embryo. Mouse embryos at different morphological stages in the transition from morula to blastocyst were analysed for the qualitative pattern of their polypeptide synthesis. The first appearance of the individual species of polypeptides specific to trophectoderm or ICM occurred progressively over this developmental period. Populations of inside cells recovered from morulae and early blastocysts synthesized those polypeptides previously shown to be characteristic of ICMs at 31/2 days, but not those characteristic of trophectoderm.


Spinal cord necrosis after intrathecal injection of methylene blue. A 59 year old man had 6 ml of unbuffered methylene blue injected into the lumbar theca in an attempt to localise the source of cerebrospinal fluid rhinorrhoea. After injection of the dye he became shocked, and within the next few days he developed a mild paraparesis which subsequently progressed to a total paraplegia. The distribution of the spinal cord damage found at necropsy, eight and a half years after injection of the dye, is described and its relationship to the clinical picture discussed.


Prospective randomized comparison of propylthiouracil. Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.


Transient hyperthyroidism in patients with lymphocytic thyroiditis. We have studied seven episodes of transient hyperthyroidism in three men and one woman, aged 19 to 38 years. No patient had fever or neck tenderness. All had palpable thyroid glands. Elevated serum thyroxine values persisted for 1 to 3 months. Thyroid131I uptake at 6 and 24 hours was low (1 to 3%). Erythrocyte sedimentation rates were normal or only slightly increased. Needle biopsy in four patients and a thyroidectomy specimen in one patient, all taken during the hyperthyroid phase, showed lymphocyte infiltration and extensive follicular disruption without oxyphilia. There was no evidence of granulomatous thyroiditis. Thyroglobulin antibodies were normal in all. In three patients, transient hypothyroidism followed the hyperthyroid episode. In two patients, the condition was recurrent. The findings are compatible with transient unregulated discharge of thyroid follicle content in some patients with lymphocytic thyroiditis. Recognition permits avoidance of unnecessary treatment with surgery, radioiodine, or antithyroid drugs.


[Lymphoblastic lymphosarcoma of the stomach (author's transl)]. A case of primary lymphoblastic lymphosarcoma of the stomach, concerning a 15 year old boy, is described. The problematic of such cases is discussed in the light of the respective literature together with the own observation. Diagnostic, therapy and course of the case are reported on. It is emphasized that benign pseudolymphoma of the stomach must be considered in the differential diagnosis. The necessity of an optimal cooperation between internal gastroenterology, roentgenology and pathology in such cases is stressed. It is pointed out that the quality of the preoperative diagnosis mainly depends on endoscopy and histology.


[Enniatin B synthesis by a Fusarium sambucinum Fuck culture]. Three fungal strains belonging to the genus Fusarium Lk. ex. Fr. (F. sambucinum Fuck. 52377, F. avenaceum (Fr. Sacc.) 52311, F. gibbosum App. et. Wr. emend Bilai 52021) whcih form 800-1200 mg of enniatin B per litre during submerged cultivation have been selected. The morphology of F. sambucinum 52377 in the course of growth and production of enniatin B on the selected medium is described. The maximum accumulation of the product is found at the stationary growth phase. The active accumulation of fatty inclusions during this period suggests the participation of metabolism of fatty acids in the biosynthesis of enniatin B.


Current status of intrathecal chemotherapy for human meningeal neoplasms. Progress in clinical intrathecal chemotherapy has been slow, and a number of new problems have been encountered. The most significant recent developments include the: 1) success of adjunctive intrathecal chemotherapy in the prevention of meningeal leukemia; 2) recognition and characterization of a necrotizing leukoencephalopathic reaction associated with intrathecal methotrexate therapy; 3) demonstration of the efficacy of intraventricular chemotherapy via an Ommaya reservoir; 4) delineation of the clinical pharmacology of intralumbar and intraventricular methotrexate; and 5) identification of an urgent need for new drugs and techniques for intrathecal administration.


[Pulmonary ultrastructural changes in dogs following experimental hemorrhagic shock (author's transl)]. The authors have studied the ultrastructure of the lung in dogs following experimental hemorrhagic shock. They found intra-alveolar edema, red cells in the alveolar sac, disappearance of the substance of the lamellated osmiophilic bodies and cellular degeneration. Correlation among these alterations and increase of capillary permeability as well as consumption of surfactant secretion were established.


[So-called biliary lithiasis after vagotomy]. Reconsidering the problem of biliary lithiasis in the patient operated for gastroduodenal ulcers, and carrying out an analysis of 1 200 vagotomized patients, biliary lithiasis was noted in 11 of them. The authors make a review of the pathologic physiology of this association. The fact is stressed that biliary lithiasis following vagotomy is more likely a case of biliary lithiasis that has not been known to exist before surgery and that was not recognized during the surgical intervention. A larger statistical analysis could demonstrate that the incidence overlaps the general frequency of biliary lithiasis in a randomly investigated population.


[Anatomoclinical aspects of portal thrombosis]. The author presents 65 cases of portal thromboses, of which 18 were isolated, 34 associated with liver cirrhosis and 13 occured after surgery for porto-caval anasthomosis. Spontaneous thromboses were of the troncular type in 61,5% of the cases, extensive in 32,7% and radicular in 5,8%. In the group of isolated forms those of the extensive type were predominant (50%), while in those associated with cirrhosis, troncular thromboses were more frequent (73,5%). In 7 cases termino-lateral antro-porto-caval thrombectomy was performed with immediately favourable results in 3 cases, of which one was maintained in time as an extra-hepatic block.


[The computed tomography of the malignant thoracic space-occupying process under special consideration of radiotherapeutic points of view (author's transl)]. The data of 70 patients with a malignant thoracic space-occupying process were compared in order to find out the differences between computed tomography and conventional X-ray diagnosis (thorax radiography, hilum tomography), the radiotherapeutic aspects of these methods being taken under special consideration. Computed tomography is excellently suited for the establishment of therapeutic schemes because it is the only technique producing individual cross-sectional views of the thorax which are in correct scale and have a high resolving power. Contrary to thorax radiography and hilum shadow, the computed tomography offers some additional diagnostic information in several special fields.


[Anatomoclinical correlations in postoperative acute thyrotoxic crisis]. Analysis of 26 cases with thyreotoxic crisis following surgery on an anatomo-clinical basis shows an extensive lesional polymorphism in the stroma and the parenchyma of the thyroid gland, indicating the absence of morphologic remission after preoperative preparation. Prolonged preoperative treatment, following evident clinical improvement, may avoid the development of postoperative crisis.


[Transcecal intubation of the small intestine]. The experience with trans-cecal intubation of the small intestine in 19 patients is presented. In author's opinion trans-cecal intubation has an advantage over other methods of enterostomy.


[Polyps; rectocolic polyposis. Etiopathogenic and anatomoclinical data. Results]. The authors statistic concerns 370 interventions for adenomatous polyps and rectocolic polyposis (105 segmental exereses, 32 total or sub-total rectocolectomies, 233 direct, endo-anal or laparocolotomy electroresections). The necessity is stressed of the early detection of isolated, or of multiple polyps, or of potentially malignant polyposis, either genetically inherited or acquired, and on their radical extirpation from the beginning, an attitude that improved late oncologic prognosis (98% survivals after 5 years).


[Supression of angiotensin II-induced contraction of the isolated guinea pig ileum by alveolar surfactants (author's transl)]. The guinea pig alveolar surfactant reduces the contraction of the isolated guinea pig ileum, induced by Angiotensin II. It is tentatively proposed, that the surfactant system suppresses the reactivity of lung blood vessels towards contacting stimuli.


Treatment of methyl mercury poisoning in mice with 2,3-dimercaptosuccinic acid and other complexing thiols. Treatment with 2,3-dimercaptosuccinic acid was more effective than N-acetyl-DL-penicillamine and monomercaptosuccinic acid in mobilizing mercury from mice after the injection of methyl mercuric chloride. Dimercaptosuccinic acid treatment started 4 days after the mercury injection and given for 8 days at a dose of 1 mmol SH/kg per day removed more than 2/3 of the mercury in the brain, while acetylpenicillamine and mercaptosuccinate correspondingly removed less than 1/2 of the brain deposits. Neither treatment with 2,3-dimercaptorropano-1-sulphonate nor with a new thiolated resin, mercaptostarch, mobilized significant amounts of mercury from the brain. Since the toxicity of dimercaptosuccinate seems to be almost as low as that of D-penicillamine this dithiol may provide a potentially useful agent in clinical poisoning due to methyl mercury.


Lithium neurotoxicity. I. The concentration of lithium in dopaminergic systems of rat brain determined by flameless atomic absorption spectrophotometry. Severe neurotoxicity has been reported in patients receiving combinations of lithium and butyrophenones and halogenated phenothiazines and the suggestion has been made that lithium is preferentially concentrated in dopamine systems in brain. Conventional flame atomic absorption spectrophotometry does not allow analysis of sufficiently small samples of brain tissue to allow accurate association with specific transmitter systems, although previous reports have suggested that lithium is concentrated in the striatum. A method has been developed using flameless atomic absorption spectrophotometry to allow accurate measurement of lithium concentrations in 10--100 ng fresh weight of brain tissue. Using this technique in experiments where rats were fed lithium over a period of three weeks, we could not confirm a direct association of lithium with an area predominetly served by dopamine transmitters.


[Substantiation studies for a method of enriching sour milk products with essential fatty acids]. Comparative investigations were conducted to produce arguments in favour of technology employed in preparing special acidified dairy products with an elevated proportion of polyunsaturated essential fatty acids for baby and dietetic nutrition. These investigations included a study into oxidative changes occurring in the vegetable oil during preparation of acidified milk by following two technological patterns that provide for introduction of the vegetable oil into the milk prior to its souring and into sour milk.


Measurement of plasma and erythrocyte chlorpromazine and N-monodesmethylchlorpromazine levels by gas chromatography with a nitrogen sensitive detector. A new gas chromatographic method, employing a nitrogenphorphorus sensitive detector, for the measurement of chlorpromazine and N-monodesmethylchlorpromazine is described. The application of the method to the measurement of the drugs in clinical plasma and erythrocyte samples is demonstrated. It was found that the chlorpromazine concentration in the erythrocytes is positively and linearly correlated with the drug level in the plasma. However, a 4-fold inter-individual variation in the erythrocyte/plasma concentration ratios was evident. The concentration of the metabolite in the erythrocytes was found to be up to 27% of that of the parent compound. Chlorpromazine was unstable in palsma but stable in erythrocytes during a week's storage in the dark at -20 degrees. The possible clinical implications of our findings are discussed.


Glutathione turnover in isolated hepatocytes. Isolated hepathocytes lost about half their content of GSH when treated in vitro with 90 nmol of diethylmaleate per 10(6) cells. Within one hour GSH started to accumulate in the cells, and the rate of accumulation was taken as a measure of the GSH synthesis rate. The rate was affected by additions of amino acids and horse serum to the incubation medium. The methionine and cysteine uptake rates were much lower than the rate of GSH synthesis and not affected by variations in the GSH synthesis rate. The methionine and cysteine uptake rates were not affected by horse serum. It is concluded that even though exogenous sulphur-containing amino acids facilitate GSH synthesis, the hepatic cysteine pool is to a large extent replenished by endogenous amino acids derived from protein degradation. In particular, this is the case when the turnover rate of the cysteine pool is increased by drug metabolism.


Serum levels and electrophysiological effects of N-acetlyprocainamide as compared with procainamide in the dog heart in situ. The electrophysiological effects of procainamide and its major metabolite N-acetylprocainamide were tested and compared on the heart of the anaesthetized dog by means of His bundle electrography and programmed electrical stimulation. Both drugs exerted a negative chromotropic effect. They also increased intra-atrial and intraventricular conduction times; procainamide was, however, the more potent of the two drugs. In contrast to procainamide, N-caetylprocainamide did not increase His-Purkinje and atrioventricular nodal conduction times, and at the lowest dose employed, atrioventricular nodal conduction times were decreased during atrial pacing. Both drugs increased the functional and effective refractory period of the right atrium and ventricle. N-acetylprocainamide increased the functional refractory period of the atrioventricular node, but to a lesser extent than procainamide.


Simultaneous and specific determination of proxyphylline, theophylline and other xanthine derivatives in serum by high pressure liquid chromatography. A HPLC-method for rapid, simultaneous and specific determination of proxyphylline, theophylline, glyphylline, theobromine, caffeine and 3-methylxanthine using 8-chlorotheophylline as internal standard is presented. Using 20 microliter deproteinised serum samples for injection, the the detection limits for theophylline and proxyphylline are about 0.040 and 0.055 microgram per ml serum or plasma, respectively, and the corresponding sensitivities are about 0.033 and 0.048 microgram compound for 0.0044 absorbance units at 280 nm. In duplicate analyses the coefficient of variation is less than 3%. A number of frequently used drugs did not interfere in the analyses of serum samples from patients under treatment or in experiments with drug additions to serum samples.


Myocardial pharmacokinetics of lithium in vitro. The myocardial pharmacokinetics of ionised lithium were investigated in isolated, intact rabbit hearts, which were retrogradely perfused with a modified Krebs-Henseleit solution containing lithium in a concentration of 5 mM. The rate of myocardial accumulation of lithium as a function of time was indirectly followed at constant coronary flow by means of determination of the lithium content of fractional samples of the coronary output of perfusate collected during the lithium perfusion period. The disposition rate of lithium from the myocardium was similarly determined with respect to the time lapse after the perfusion had been switched over to a lithium-free liquid. The accumulation and disposition processes were found to fit bi-exponential functions, as an expression of the myocardium behaving as a two-compartment system obeying apparently first order, linear kinetics with respect to ionised lithium. A pronounced decrease of the uncomposite elimination rate constants k10 and especially k21 was observed after continuous perfusion with 5 mM lithium perfusion liquid for about 30 min. During this perfusion period at steady state, an absolute increase of myocardial lithium accumulation obviously took place. A possible correlation of these findings to the cardiac effects of lithium is discussed.


Ascorbic acid metabolism and the clinical factors which affect tissue saturation with ascorbic acid. The factors which give rise to tissue desaturation of ascorbic acid are classified and discussed. Nutritional deprivation, normal physiological factors and metabolic factors, and pathophysiological factors may all give rise to acute and continuing ascorbic acid tissue desaturation while the factors continue to operate. Nutritional desaturation can easily be rectified by providing supplementary Vitamin C in adequate dosage. The other factors can only be rectified when the causative mechanism is arrested. Iatrogenic desaturation may be produced by aspirin and several other drugs. While causative factors excluding that of nutrition are operating, it is very difficult if not impossible to restore normal tissue values of ascorbic acid. In consequence side effects which arise from supplementary Vitamin C administration do not arise in these circumstances. The supplementary Vitamin C administration is defined as compensatory administration of Vitamin C. In healthy individuals administration of supplementary Vitamin C can be defined as (large doses). Such large doses may give rise to side effects. The mechanism by which ascorbic acid is involved in the inflammatory response is discussed.


Interaction of erythorbic acid with ascorbic acid catabolism. There exist altogether four stereoisomers of ascorbic acid. Erythorbic acid (D-isoascorbic acid) differs in the spatial configuration at carbon 5 and has less than 5 per cent of biological vitamin C activity. In guinea pigs, depending on an exogenous supply of ascorbic acid, a possible interaction of erythorbic acid with absorption, transport through the cell membranes at the tissue level, or with catabolism of ascorbic acid has been investigated. After oral administration, results suggest no difference in absorption of these two compounds from the intestine, whereas uptake by the tissues was approximately four to one in favour of ascorbic acid. Feeding experiments with erythorbic acid indicate the availability of ascorbic acid being diminished by 40-60% when administered together with erythorbic acid. Kinetic data on the catabolism of ascorbic acid showed a significant reduction in half-life (50% of the dose excreted) of the vitamin caused by administration of erythorbic acid. The results suggest the oxidative destruction of ascorbic acid in the liver being significantly accelerated. Thus, ingestion of erythorbic acid interacts with newly introduced ascorbic acid by enforcing the breakdown of ascorbic acid. Implications of these findings for the metabolism, availability and nutritional status of ascorbic acid in humans will be discussed.


Ocular neovascularization. The Krill memorial lecture. The various vascular systems of the eye can undergo new vessel formation. In this presentation, I discuss new vessel growth in the cornea, lens, iris, ciliary body, choroid, retina, and optic nerve head. No single factor can explain all cases of ocular neovascularization; instead there are multiple factors which can affect the various susceptible vessels. Among the known vasculognic factors are: inflammation and its products, a hypoxic retina diffusable factor, the "tumor angiogenic factor," and possibly an aging factor. The different ocular beds possess differing sensitivity to the various vasculogenic stimuli; the iris and choroid being most sensitive and the retina and ciliary body least sensitive to such stimuli. Retinal neovascularization requires both a biochemical factor and a diseased retinal vascular bed for its induction. Ocular neovascularization is a dynamic process which requires a persisting stimulus or else the new vessels tend to regress. The normal eye seems to possess at least two antivasculogenic agents.


Acute toxicity of penicillic acid and rubratoxin B in dogs. The effect of intraperitoneally administered penicillic acid, a mycotoxin produced by several species of Penicillium and Aspergillus, on female dogs of mixed breeding was determined by serum tests, by observation of clinical signs and survival times, and by evaluation of gross and microscopic lesions. Combination studies employing penicillic acid and a second mycotoxin, rubratoxin B, also were undertaken. Post mortem examination disclosed hemorrhaging of the serosal surfaces of the abdomen of dogs receiving penicillic acid. The most significant histologic change observed in penicillic-acid-treated dogs was congestion and dilatation of hepatic sinusoids. Extensive hepatic changes of the liver were noted only in the dog receiving 20 mg/kg penicillic acid. There was no evidence of parenchymal necrosis in any of the liver samples examined from animals given penicillic acid. A predominently peripheral lobular depletion of glycogen in parenchymal cytoplasm also was seen in liver sections from animals exposed to penicillic acid. Although slight decreases in lactic dehydrogenase were observed, no trends were detected in the several blood enzymes and serum constituents examined that could be specifically related to penicillic acid intoxification. Glutamic-oxaloacetic transaminase, lactic dehydrogenase and alkaline phosphatase activities and survival time varied in relation to duration of exposure and total dose of rubratoxin B administered. The lesions in animals injected with 1.0 mg/kg rubratoxin B consisted of mild hepatic necrosis and degenerative changes in renal tubular epithelium. An additive effect due to the combined administration of penicillic acid and rubratoxin B was observed only by an elevation in serum sodium and chlorine levels.


Efficacy of seven anthelmintics against Ancylostoma ceylanicum in the golden hamster, Mesocricetus auratus. In an experimental patent infection of Ancylostoma ceylanicum in golden hamsters the efficacy of seven anthelmintics was tested; bephenium hydroxynaphthoate, tetramisole, tetrachlorethylene, phenylene 1,4-diisothiocyanate, thiabendazole, parbendazole and mebendazole were studied. Mebendazole was the most effective, with parbendazole, phenylene 1,4-diisothiocyanate, thiabendazole and bephenium hydroxynaphthoate also satisfactory. Tetrachlorethylene and tetramisole were the least effective in our screen.


[Fetal lung maturity in differen abnormal pregnancies (author's transl)]. The influence of pathological situations to fetal lung maturation during the last 9 weeks of pregnancy was studied. Lung maturity was determined by four different methods, analyzing the concentration of surfactant in amniotic fluid L/S ratio was measured planimetrically and densitometrically, foam test and surface tension of the liquor amnii were used on this purpose. 89 normal pregnancies for obtaining normal values served as a basis for comparison with pathological events. A general retardation of fetal lung maturity showed 26 patients with rhesus isoimmunization so as 26 patients with diabetes classes A, B and C (White). In three pregnancies complicated by diabetes class D a remarkable acceleration of fetal lung maturity was obvious. 30 patients with placental insufficiency sui generis presented a very inhomogenous development of the fetal lung, whereas in 35 patients with EPH-gestosis a minute acceleration between 33th and 37th week of gestation was found. A good correlation between all of the used methods for measuring the concentration of surfactant was noted. Best reliability in correct prediction of lung maturity showed the method of measuring the surface-tension of the amniotic fluid.


[Measurements of spontaneous pressure changes in the arterial vessels and in the tissue of bovine ovaries perfused in vitro (author's transl)]. 12 bovine ovaries were perfused in a closed circuit system using a semisynthetic hemoglobinfree perfusate. The pressure in the ovarian tissue and the arterial pressure were recorded simultaneously. Arterial and tissue pressure changes were noticed in bovine ovaries, as have been described in other species. It could be shown that pressure in the vascular system and the arterial pressure may vary independently. It appears as if spontaneous pressure changes in the in vitro perfused ovary are more pronounced in frequency and amplitude during the phase of follicle maturation.


[Chorioangioma (author's transl)].

[Chorioangioma (author's transl)]. Considering our own data and after reviewing the literature the following conclusions can be drawn: 1. In 0.41% of all births the incidence of a chorioangioma is to be expected. 2. Small chorioangiomas are much more frequent than large ones. In most cases, they occur solitary, only sometimes multiple. 3. Most of the chorioangiomas are located centrally in placental tissue or at the fetal side in relation to the chorion. 4. A classification of five histological types can be made: Type I: Endotheliomatous chorioangioma; Type II: Capillary chorioangioma; Type III: Cavernous chorioangioma; Type IV: Fibrosing chorioangioma; Type V: Fibroma. 5. There is no significant relationship to the mother's age. The incidence is higher in primipari. The rates of gestones as well as the rates of prematurity and still birth increased with these tumors. 6. Hydramnion as well as fetal complications are entailed with large or multiple tumors.


[Is there a possibility of paraplacental oxygenation of fetal blood? First results of an investigation with fluorocarbon (author's transl)]. By checking the cardiotropic effect on fetal rabbits we tried to find out weather there is a possibility of paraplacental oxygenation of fetal blood. Amniotic caves of nine fetal rabbits of 28th or 29th day of gestation are perfused with Perfluorobutyltetrahydrofuran (FX 80, 3 M Comp., St. Paul, Minn., USA) continuously. This was done by double blind investigation. The fetal heart rate is written by Hewlett-Packard-cardiotocograph. Therefore we use modificated EEG-electrodes. 48 h before we cut the spinal cord of the pregnant animals just for analgesie. So we exclude the influence of analgesics or narcotics. After complete interruption of uterine blood supply you can find an initial reduction of fetal heart rate. Using fluorocarbon we notice an increasing or stabilisation of fetal heart rate of all rabbit fetus. In comparison with control animals the difference is high significant. The cardial survival rate of four fetal rabbits treated with fluorocarbon is prolonged up to 50 min. During this time all "fluorocarbon fetus" never died earlier than the control animals. Lots of new questions are provoked by our results. One has to find an answer.


[The effect of sexual steroids on the isometric contraction of the isolated rat diaphragm (author's transl)]. The influence of estradiolbenzoate, hydroprogesteroncapronate and pregnancy on the mechanical reaction of the directly and indirectly stimulated nerve-diaphragm preparation has been the subject of this investigation. Rats were ovario-ectomized and the hormone preparations were injected subcutaneously. After a lapse of 9 days the test preparation was made. 1. Estrogen and the estrogen-gestagen combination have a similar effect on the isometric contraction of the transversely striated muscle. The times of rising and relaxation were prolonged after indirect and direct stimulation. The contraction amplitude had not altered compared to the control group. 2. Gestagens and the hormone situation of pregnancy entail, independent of the kind of stimulation, a decrease of the tension progress and the speed of the tension increase. The gestagen-treated animals underwent a shortened contraction process. These findings enable us to comment on the different efficiencies of women during various cycle phases and during pregnancy.


Intrauterine development, feto-placental function and pregnancy outcome after induction of ovulation with bromoergocryptine. 18 pregnancies occurred after treatment with bromoergocryptine in 17 patients who wished to conceive, but who suffered from anovulation of varying aetiology. The course of 15 pregnancies was uneventful. Three pregnancies ended in abortion. Nine of the 17 women had hyperprolactinemic amenorrhea. Furthermore, one woman had normoprolactinemic post-pill amenorrhea, another normoprolactinemic anovulatory oligomenorrhea and a third normoprolactinemic anovulatory regular menstruations. With the exception of one woman, all had galactorrhea. The courses of pregnancy were monitored by frequent ultrasound measurements of the fetal biparietal diameter, maternal urinary estriol excretion and radioimmunological measurements of plasma estrone, estradiol, unconjugated and immunoreactive estriol, progesterone, and HPL. All data were within the normal ranges and all babies were healthy at birth and had no teratogenic defects. The data prove the great value of bromoergocryptine in the treatment of hyperprolactinemic anovulation, sometimes even in the treatment of normoprolactinemic anovulation. Moreover, the results indicate no adverse effect on either the course or the outcome of pregnancy.


Peritoneal foreign body granulomas to keratin in uterine adenocanthoma. Four cases of well-differentiated adenocarcinoma with squamous metaplasia (so-called adenocanthoma) of the uterus were associated with granulomatous inflammation of the pelvic peritoneum. The inflammation was the result of a foreign-body response to keratin that desquamated from the surface of the tumor and was carried to the peritoneal cavity through the lumen of the Fallopian tubes. The absence of viable neoplastic cells and favorable follow-up examinations in these patients indicate that the presence of peritoneal keratin granulomas in association with endometrial adenoacanthoma should not be regarded as an indicator of metastatic spread.


Transient pseudoleukocytosis caused by cryocrystalglobulinemia. A patient with Sjögren's syndrome and cryoglobulinemia was found to have pseudoleukocytosis when a leukocyte count was performed on an electronic particle counter. This apparent increase in the leukocyte count was found to be caused by spontaneous crystallization of the cryoglobulin. Further studies showed that this phenomenon was transient. Disappearance of the spontaneous crystal formation without a change in the level of cryoglobulin suggests the possibility of an interaction between the cryoglobulin and a plasma component. Factors affecting spontaneous crystallization of cryoglobulins and the laboratory as well as the clinical implications of pseudoleukocytosis are discussed.


Angiomyxoma of umbilical cord.

Angiomyxoma of umbilical cord. A rare angiomyxoma of umbilica cord occurred in a male infant. The presence of such a tumor with its vascular component arising from a hypoplastic umbilical artery supports the hypothesis that the lesions arose through improper placental vascularization.


Benign and malignant struma ovarii.

Benign and malignant struma ovarii. Three cases of struma ovarii are reported, two of which were benign, and one which was malignant. Immunoperoxidase studies confirmed that the tumors secreted triiodothyronine and thyroxine, but no carcinoembryonic antigen nor alpha-fetoprotein. In the case of the malignant struma ovarii, the patient's thyroid was histologically normal, and thus the possibility of a metastasis to the ovary from a primary thyroid carcinoma was excluded.


A sarcoma of myofibroblasts: an ultrastructural study. A low-grade spindle cell sarcoma was shown by electron microscopy to be composed of myofibroblasts. It is suggested that the occurrence of myofibroblasts in spindle cell sarcomas might be of prognostic significance and that a systematic study to elucidate this point would be a valuable exercise.


Unusual variant of lipid-rich mammary carcinoma. A variant of lipid-secreting mammary carcinoma shared many of the features of previously reported lipid-rich breast tumors, ultrastructurally as well as clinically and by light microscopy. In addition, electron microscopy confirmed the presence of a dual-cell population where the more aggressive cell, which resembled an altered myoepithelial cell, was responsible for the lipid production. The tumor also demonstrated some similarity to medullary carcinoma and may represent a variant of this type of mammary tumor.


Nemaline myopathy.

Nemaline myopathy. Nemaline myopathy occurred sporadically in a 59-year-old woman. She had slowly progressive weakness. A muscle biopsy specimen showed nemaline rods, increased variation in fiber size, apparent loss of Type IIb fiber differentiation, and a "moth-eaten" pattern of the intermyofibrillar network. At least 44 cases of this disorder have been reported. Clinically, they showed several different modes of onset, patterns of muscle group involvement, and rates of progression. There was a suggestion of familial involvement in at least half. In addition to the presence of nemaline rods, pathological abnormalities of muscle biopsy specimens were quite variable. Results of recent biochemical studies have shown abnormal myosin in a patient with rod myopathy. A hypothesis is proposed that relates the diverse clinical and histological features of this disease to a hereditary molecular abnormality of myosin synthesis.


Gallbladder with ectopic gastric mucosa: ultrastructural analysis. The clinical and pathological findings of two patients with ectopic gastric mucosa within the gallbladder are studied and compared with the findings recorded in the literature. A contrast between incidental and symptomatic ectopia was noted in these cases. Morphologically bountiful parietal cells were noted in our symptomatic case, while sparse parietal cells were found in our incidental case.


Late complications of prosthetic heart valves. Iatrogenic lesions induced during prosthesis insertion are likely to be encountered by a pathologist examining a patient who died of late complications of heart-valve prosthesis. The lesions are classified as those that may occur in any patient who has had a heart-valve prosthesis inserted, including the iatrogenic type and those that are uniquely associated with a particular prosthesis because of its structure or design.


Subvalvular left ventricular false aneurysm complicating mitral valve replacement. Surgical replacement of the mitral valve by a prosthetic valve may lead to localized disruption of atrioventricular continuity resulting from direct surgical trauma or from delayed rupture of the weakened annulus. Such disruption leads to subepicardial hematoma formation that may remain localized if pericardial adhesions are present. Of two patients who suffered this complication, the first died of rupture of the epicardial hematoma. The hemorrhage in the second patient was contained by pericardial adhesions and had organized, thus resulting in a subannular left ventricular false aneurysm. The aneurysm was found incidentally at autopsy after the patient died of cerebral embolism from prosthetic valve thrombi.


Morphological effects of moderate diet and clofibrate on swine atherosclerosis. Early proliferative coronary atherosclerosis was produced in swine by feeding them a high-fat, high-cholesterol diet for 17 months, at which time one group of animals was killed (reference group), while the remainder was transferred for 12 months to a moderate diet that resulted in serum cholesterol levels of about 190 mg/100 ml. The moderate diet only did not decrease the size of coronary lesions, but prevented their progression. The addition of clofibrate therapy caused regression that involved a significant decrease in size, gross sudanophilia, and extent of calcification and the disappearance of foam-cell lesions. Resultant serum cholesterol levels appear to be more important than the amount of dietary cholesterol in the progression, prevention, and regression of swine coronary atherosclerosis.


Biochemical effects of moderate diet and clofibrate on swine atherosclerosis. Aortic atherosclerotic lesions were induced in swine by feeding them an atherogenic diet for 17 months. The effect of a moderate diet (up to 8 gm of cholesterol per day), with or without added clofibrate therapy, for the subsequent 12 months was assessed by biochemical analysis of carefully dissected lesions and adjacent nonlesion areas. The moderate diet alone prevented "progression," except for accumulation of free cholesterol and enhancement of total protein and collagen synthesis, and caused regression of DNA concentration to nonlesion levels. The addition of clofibrate therapy enhanced regression, with significant decreases in DNA and esterified cholesterol concentrations and in the rate of DNA synthesis. Extrapolation of these results to man suggests that a "sensible" level of dietary lipid may be prophylactic against further progression, while addition of an effective hypolipemic drug may be therapeutically useful.


Cardiovascular manifestations of Pseudoxanthoma elasticum. Autopsies were performed in three cases of pseudoxanthoma elasticum (PXE) to evaluate the cardiovascular changes. The endocardial lesion characterized by intimal fibroelastotic thickening and disorganization, fragmentation, and calcification of elastic fibers in the deeper endocardial layers is unique histologically. Severe atherosclerosis was present in all cases and resembled that encountered routinely. Fragmentation and degeneration of the elastic laminae of muscular arteries was followed by vascular calcification that could not be distinguished morphologically from Mönckeberg's arteriosclerosis. All three cases showed striking initimal fibroelastotic thickening, particularly in intrarenal arteries, resembling that seen in hypertension, although only one of the subjects was hypertensive. It would appear that the metabolic defect in PXE predisposes to the premature onset and accelerated development of commonly encountered vascular aging processes, and that the endocardial lesion is the only specific cardiovascular manifestation of the disease.


Resolution and repair of elastic tissue calcification in pseudoxanthoma elasticum. Biopsy specimens of a skin lesion from a patient with pseudoxanthoma elasticum were obtained at the beginning and end of a 1 1/2-year period of clinically documented regression of the lesion. Light microscopic studies of these specimens showed that, during the period of regression, there was a decrease in the number of abnormal calcified elastic fibers in the dermis. Electron microscopic findings were interpreted as indicating breakdown and removal of mineralized elastic fibers at the beginning and formation of new elastic fibers at the end of the regression period. Cytoplasmic processes of active fibroblasts were intimately associated with fibers undergoing dissolution. The case thus represents a clinically and morphologically documented example of resolution and repair of elastic tissue calcification.


Foamy myocardial transformation of infancy: 'lipid' or 'histiocytoid' myocardiopathy. Two cases of a distinctive infantile myocardiopathy were studied by light and electron microscopy. They represent the 15th and 16th reported examples of this condition, and include the first associated with morphologically classical endocardial fibroelastosis. The condition is characterized by the presence of clusters of foamy or granular cells scattered throughout the myocardium. Ultrastructural studies indicate (1) that lipid storage is not a feature of the condition, and (2) that the abnormal fibers are characterized by a reduced number of fibrils and an increased number of mitochondria. It is proposed that the lesion should be called "foamy myocardial transformation of infancy," and it is speculated that the condition is an acquired metabolic disorder, perhaps occurring in patients abnormally predisposed to such an acquisition.


Experimental myositis ossificans: cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen. Bone matrix gelatin, prepared by chemical extraction of soluble noncollagenous proteins, was half digested with a chromatographically purified collagenase. The residue was placed on one side and autologous muscle on the other side of cellulose acetate membranes in diffusion chambers and tissue cultures. In this avascular system, the muscle septa connective tissue proliferated and differentiated into cartilage. Muscle tissue cultured in media conditioned with matrix residues and then transferred into a vascularized muscle pouch differentiated into cartilage and bone. These observations form the basis for a working hypothesis that myositis ossificans is a response of new populations of proliferating intramuscular connective tissue cells to a bone matrix-derived diffusible molecule.


Congophilic angiopathy and cerebral hemorrhage. All the cases of spontaneous intracerebral hemorrhage that were autopsied between 1965 and 1976 at at Kuakini Hospital, Hawaii, were analyzed to determine the frequency of coexistent cerebral congophilic angiopathy. Seven of 75 cases (9.3%) were confirmed to have deposition of amyloid in the intracerebral vessels by means of polarized light microscopy and electron microscopy. The cerebral congophilic angiopathy was found to have predilection for aged patients and women (ratio of 6:1). Diabetes mellitus, hypertension, atherosclerosis, systemic amyloidosis, and paraproteinemia did not appear to be associated with this change. There is, however, a strong correlation between classic as well as compact senile plaques and this vascular lesion.


Pathology of the adrenal gland in refractory low-renin hypertension. The adrenal glands of 13 patients with low-renin hypertension that was refractory to medical treatment were examined. Eight patients underwent total adrenalectomies and five underwent subtotal adrenalectomies. All of these patients had grossly visible adrenocortical changes. Ten patients had gross cortical nodules, and ten showed nonnodular cortical hyperplasia; seven had both. All ten patients with gross nodules had microscopic nodules as well. Of the 13 patients with low-renin hypertension, 12 (92%) had substantially lower blood pressure postoperatively without medication. During a follow-up period ranging from 14 to 38 months, three patients were normotensive without medication, nine patients had lowered blood pressures without medication and were easily maintained normotensive on antihypertensive medication, and one patient had no significant reduction in blood pressure postoperatively and no improvement in blood pressure control with antihypertensive drugs.


Methylmercury chloride induces learning deficits in prenatally treated rats. Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 X 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.


The index line as a new aid in clinical and forensic toxicology. On behalf of the German Federal Ministry for Research and Technology, we investigated the use of electronic data processing for clinical toxicological purposes. Initially, sufficient funds were available for a comprehensive approach to the problem and programs covering the following areas were established: 1. A casuistic data program; 2. an identification program for wild fruits; 3. a program for the identification of tablets by their shapes. Due to a subsequent lack of funds, it was necessary to develop a partial solution: this solution is what we call the Index Line. The Index Line--limited data on poisonings--should enable the user to receive information by telex from the German Institute for Medical Documentation and Information, i.e., information on "who has what, where". As a first step the continuous Index Line registration of all cases of poisoning recorded at the poison control centers in Munich, Freiburg, Hamburg, and Nürnberg as well as at the State Institute for Food, Pharmaceutical and Forensic Chemistry in Berlin was founded in 1975. To participate in the program, complete instructions are necessary.


Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid. To characterize the hepatic biotransformation in the chimpanzee of the primary bile acid chenodeoxycholic acid (chenic) and its major bacterial metabolite lithocholic acid (lithocholic) a mixture of trace amounts of 14C-lithocholic and 3H-chenic was injected intravenously into two animals with a bile fistula; the chemical form of radioactivity appearing in bile was inferred using thin layer chromatography. About 80% of chenic, and 70% of lithocholic was recovered in 90 min. Chenic was completely conjugated in bile, appearing predominantly as chenyltaurine (52%) and chenylglycine (37%). An unidentified conjugate (about 11%) was also found. Lithocholic was excreted completely as taurine and glycine conjugates, but the majority (63%) of conjugates was sulfated. Sulfation increased progressively with time, and lithocholylglycine was sulfated more than lithocholyltaurine. We conclude that the chimpanzee is similar to man in that the secondary bile acid lithocholic is efficiently sulfated. The chimpanzee thus differs from the baboon and rhesus monkey which sulfate lithocholic poorly. However, the chimpanzee differs from man and is similar to the baboon and rhesus monkey in showing preferential conjugation of bile acids with taurine. The results imply that hepatotoxicity caused by chenic, which is well documented in the rhesus monkey and baboon and has been related to defective lithocholic sulfation, should not occur in the chimpanzee.


Effect of selenium on the organ distribution and binding of bismuth in rat tissues. Subcutaneous administration of bismuth, both single and multiple, resulted in deposition of this metal mainly in the kidneys which contained over 50% of the 'accessible pool' of bismuth. In the kidneys bismuth was bound mainly by the soluble fraction in which it was complexed with a protein of molecular weight of about 7000. Multiple administration of bismuth increased the level of this protein. Selenite administration brought about an increase in the 'accessible pool' of bismuth, probably due to a drop in excretion, and also changes in the organ distribution of this metal. The retention in the kidneys was diminished while those in the liver and in other tissues were augmented. These changes were accompanied by a change in the chemical form of bismuth present in the kidneys manifested by the total disappearance of the protein complex of molecular weight of 7000. The increased synthesis of this protein due to bismuth administration was not abolished completely.


Selective cytotoxic actions of aspirin on parietal cells: a principal factor in the early stages of aspirin-induced gastric damage. Electronmicroscopic observations are reported on the effects of orally administered aspirin on the rat gastric mucosa to establish the cytotoxic events that occur during the early stages of the development of gastric damage induced by this drug. The results show that aspirin, apart from damaging superficial mucous cells, causes selective damage to the acid-secreting parietal cells located deep in the fundic mucosa. It is suggested that the selective accumulation of salicylates in the parietal cells may account for the specific cytotoxic actions of aspirin on these cells.


The diagnosis of organophosphorus fatal intoxication by the AChE activity in CSF. A preliminary test for the diagnosis of intoxications with organophosphorous pesticides in fatal cases is described, based on the fact that these compounds inhibit AChE activity. For this purpose we measured AChE activity in CSF in 30 samples from fresh bodies autopsied after traffic accidents and in six after poisoning with organophosphorous insecticides. In order to exclude any other effect on the postmortem inactivation of the enzyme e.g. putrefaction we determined the AChE activity under different conditions. Thus we confirmed that in the reference samples, regardless the conditions, the activity of the enzyme was detectable at least 48 h after death, while in cases of poisoning the detection of AChE was inevitable early after death.


[The vessels of the inner ear (author's transl)]. The inner ear as an example of a highly specialized sensory organ also possesses a highly specialized vascularisation. This represents an impressive example for a reasonable adaption of the terminal blood vessels to a specific function of the organ fulfilling more than only the nutrition. In this paper the microvascular bed of the cochlea is examined using both the injection method of the vessels and the biomicroscopic observation in vivo. The combination of these technics supported by histologic and stereoscan microscopic examinations has made it possible to give an account of the functional  morphology of the inner ear vessels. As a detailed structural analysis of the vessels morphology with the help of dyes that fill the whole of the vessels space  (i.e. Berlin blue) is not possible, perfusion experiments with silver nitrate were performed on the inner ear. After the perfusion the vessels are cleaned again, the silver however imbibes the intercellular reticular substances and after exposure produces a continous and sharp framework of the endothelium and--when present--muscular cells, thus showing the angioarchitectural contours. There is a very clear division of the cochlear vessels in a three dimensional space: The arterial and venous vessels are vividly separated from one another, forming two systems of microvascular units in the lateral wall and the spiral lamina. Each unit begins with special blood vessel convoluts in the modiolus, consisting of loops of arterioles. They are weakly muscularized whereas no muscle structures are seen elsewhere in the other parts of the inner ear vessels. There are no a.-v. anastomoses or sphinkters at all. The function of the vessel loops in the modiolus is to flatten the pulse wave as well as to regulate the blood flow in the microvascular bed by vasomotion. This was proved by statistical examinations of 1200 measurements of the widths of the vessels at several points of the cochlea in a blind study with and without vasoactive drugs. The terminology of the vessels is not standardized. The nomenclature in this paper has regard to the classification of the vessels, the course and the topographic localisation. Silver staining reveals changes in the form of the endothelium cells from the arterial towards the venous end. While the arteries show a long stretched spinle or lancet like form they change over blunt, oval, triangular or rhomboid forms into polygonal cells with spiked border lines at the venules. All experiments together give an account that the blood supply of the inner ear is in close correlation with the blood supply of the brain and too possesses autoregulative mechanisms, which must be localized in the convoluts at the beginning of every microvascular unit of the cochlear vessels.


[Anatomy, variations and malformations of the vessels of the head and neck region (author's transl)]. After a short review of developmental data concerning the head and neck arteries, the normal conditions, variations and malformations of single arteries are described. Special attention is paied to the skeletotopic and topographic relations of the arteries. In every bigger vessel its length, position, origin and branches are described, and in most cases are also demonstrated by diagrams and tables. As the aortic arch may also reach the neck region, its variation and malformations as well as the variations of its branches are mentioned. The variations and the malformations of the inominate artery, of the common carotid artery, as well as of the external and internal carotid arteries are described. The practical importance of these variations is stressed. Upon description of variations and malformations anatomical, surgical und roentgenological findings described in literature, as well as personal experiences are considered. Special attention has been paied to the variations of the circulus arteriosus Willisi, to the persistence of the presegmental arteries and to the possibility of formation of a by-pass in occlusion or aplasia of cerebral arteries. The position of the subclavian artery, its variations and the variations of its branches are described. After a short embryological introduction, the variations of the venous system and its anastomoses are described. At the end, the main variations of the big lymphatic vessels in the neck are mentioned.


[Surgery of neck vessels (author's transl)]. The progress in vascular surgery offers to the otolaryngologist a remarkable increase of his surgical activities. This is especially true in the field of tumor surgery in the region of the carotid arteries and the jugular vein (e.g. removement of carotid body-tumor, lymphnode deposits by neckdissection etc.). Both the ligature of the internal as the common carotid arteries should be--when ever possible--avoided. The method of choice is an arterial reconstruction (by direct vascular suture or an autogenous venous graft respectively a Dacronprosthesis). In the presence of wound infection or damaged soft tissue by radiation any vascular repair is contraindicated except of an extra-anatomic bypass-procedure. Every otolaryngologist engaged with great neck surgery should be familiar with the basic principles of vascular surgery and should keep a set of vascular instruments available. Some neck interventions, dealing with the great vessels, are best performed in teamwork of laryngologist and vascular surgeon.


The growth kinetics of synovial fibroblastic cells from inflammatory and noninflammatory arthropathies. The growth kinetics of subcultured human synovial fibroblasts from 16 patients with inflammatory and noninflammatory arthropathies were studied in antibiotic free media. The experimental design allowed a clear distinction between the growth rates and final saturation densities achieved. The effects of refeeding and of the serum concentration were evaluated for each line. Inflammatory lines achieved significantly higher final saturation densities and growth rates than noninflammatory lines for most protocols, but the differences between rheumatoid and nonrheumatoid groups were less marked. Inflammaroty fibroblasts demonstrated a greater independence to nutritional and growth stimulatory factors in their microenvironment than noninflammatory fibroblasts.


[Angiography of face and skull base (author's transl)]. The anatomic and technical conditions of the angiography of the face and the skull base are described. The significance of the catheter technique for selective demonstration of branches of the external carotid artery is stressed. The communications between the internal and the external carotid artery are discussed as well as the angiographic problems of arteriovenous fistulae and of hypervascular tumors. The selective angiography of the internal and the external carotid artery is an important tool of neuroradiology. By exact anatomic correlation of individual vessels and pathologic processes of the face and the skull base it is of interest also for oto-rhino-laryngology. Because of pain associated with the injection of contrast material general anaesthesia is deriable for the angiography of the external carotid artery.


[Antimalarial 6-aminoquinolines. VII. 2- and 4-Alkoxy derivatives of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline (author's transl)]. 19 derivatives, 10 a--t, of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline (1a) with alkoxy-, hydroxy-, and methylmercapto substituents in 4- and/or 2-position were synthesized with the aim of studying the influence of these substituents on antimalarial activity and toxicity of 1a. The alkoxy derivatives of 1a are highly active against P. vinckei (mouse). The 2- and 4-hydroxy derivatives, 10 l and 10 m, are inactive.


Uridine enhances the chemotherapeutic action of the 4'-demethylepipodophyllotoxin-thenylidene-glucoside (VM 26)-cyclophosphamide combination on i.m. implanted Ehrlich carcinoma. The chemotherapeutic effectiveness of the simultaneously used combination of 4'-demethylepipodophyllotoxin-thenylidene-glucoside (VM 26) and cyclophosphamide was significantly enhanced by uridine in i.m. implanted Ehrlich carcinoma without increasing toxicity when uridine was applied sequentially at an interval of 20 h.


Pharmacokinetic studies of the antiarrhythmic drugs ajmaline and N-propylajmaline bitartrate in dogs. A rapid, sensitive fluorometric method for the determination of ajmaline and N-propylajmaline (NPA) was used to follow serum concentrations after an i.v. administration of ajmaline, after an oral administration of ajmaline, and an oral dose of NPA bitartrate (NPAB) in beagle dogs. Ajmaline was eliminated from serum with an apparent half-life of approximately 1 h and NPA with one of approximately 4 h. 1 h after i.v. and oral administration of 50 mg of ajmaline the serum levels were of the same order of magnitude. The bioavailability of oral ajmaline, calculated from the area under the serum concentration/time curves, was about 90%. The peak serum concentrations of ajmaline and NPA after a single oral dose of 50 mg of ajmaline and NPAB were about 1.4 microgram/ml and 0.6 microgram/ml, respectively, the latter calculated as its bitartrate, with about the same peak time: 1 h.


Effects of diltiazem hydrochloride (CRD-401) on hepatic, superior mesenteric and femoral hemodynamics. The effects of d-3-acetoxy-cis-2,3-dihydro-5-[2-(dimethylamino)ethyll-2-(p-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one hydrochloride (diltiazem hydrochloride; CRD-401) on the hepatic, superior mesenteric and femoral arteries were investigated in dogs. The results obtained were as follows: 1. At an i.v. dose of 100 microgram/kg, CRD-401 lowered the mean aortic blood pressure (-5%). It also decreased the diastolic aortic blood pressure (-11%) but did not affect the systolic aortic blood pressure. 2. The mean aortic blood pressure decreased after injection of CRD-401, but the blood flows in the hepatic, superior mesneteric and femoral arteries increased to 33%, 31% and 17%, respectively, more than did the control values and the vascular resistances of these arteries decreased by 25%, 27% and 17%, respectively. The present study obviously demonstrates that CRD-401 has vasodilating action on the hepatic, superior mesenteric and femoral arteries.


[Haemorrhage and haemostasis in face, visceral cranium, neck and middle ear region (author's transl)]. Head and neck surgery is accompanied by more or less heavy tendency to bleed. Spontaneous bleeding will occur, because of general and local peculiarities depending on the vascularisation of this region. The general part of the paper deals with normal haemostasis and the diagnosis of haemorrhagic diathesis. This part also shows simple surgical measures in order to stop bleeding. The special section of the paper explains bleeding problems by case history. Here mainly complications are shown exceedingly imporant to the ENT Doctor, because of their more common frequency i.e. nose-bleeding, adenotonsillextomy as well as alarming haemorrhage from great vessels of the neck (arrosion bleeding of the carotid artery, lesion due to accidents and following necksurgery).


Effects of diltiazem Hydrochloride (CRD-401) on renal hemodynamics of dogs. The effect of d-3-acetoxy-cis-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepine-4(5H)one hydrochloride (ditiazem hydrochloride, CRD-401) on renal hemodynamics was investigated in 18 mongrel adult dogs, and the following results were obtained. 1. Renal blood flow (RBF) was significantly increased following i.v. injection of 100 microgram/kg of CRD-401, in spite of decreased ao-tic blood pressure. Moreover the same dose of the drug elicited greater increase in RBF while the renal arteries were perfused at a constant pressure in order to prevent the decrease in systemic blood pressure from affecting RBF. These results suggest that CRD-401 has a vasodilatory action on the renal arteries. 2. The increasing rate of RBF and decreasing rate of renal vascular resistance (RVR) after injection of the drug into the renal artery at the dose level of 3 microgram/kg were found to diminish by pretreatment with hexamethonium (C6) before CRD-401. The vasodilating effect of CRD-401 on the renal arteries was therefore assumed to be more prominent in a state of renal arterial constriction. 3. RBF and RVR were increased and decreased, respectively, in proportion to the doses of CRD-401 ranging from 3 to 100 microgram/kg, the vasodilating action of CRD-401 on the renal arteries increased dose-dependently.


Improvement of perfusion flow in the isolated rat liver under the influence of streptase. Autohistoradiographic aspects of 125I-labelled fibrinogen deposition. The dynamics of the fibrinoplastic process were studied in rat isolated liver, perfused in normothermia with a synthetical medium. For the autohistoradiographical study, 125I-labelled fibrinogen was added to the perfusing medium. The historadiograms obtained suggest that the main link in the rise of trans-hepatic vascular resistance is thickening of the fibrin muff of the sinusoids. Consequent reduction of the capillary permeability determines favourable conditions for stasis and massive precipitation of fibrinogen under the form of fibrin thrombi into the intrahepatic vessels. Streptase addition to the perfusion medium prevents the intervention of these mechanisms during the studied period.


Acute, subacute and chronic toxicity of oxepinac. The acute, subacute and chronic toxicity of 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (oxepinac) was investigated in several animal species. The LD50 value was lower in rats than in rabbits, mice and dogs. The major cause of death was perforative ulcer in the gastrointestinal tract. Long-term study in rats revealed that oxepinac produced no hematological, blood chemical and pathological changes except for minor anemia and fatal ulcer formation occurring predominantly in females. Oxepinac proved to be less toxic than indometacin in chronic toxicity in rats.


Teratogenicity study of oxepinac in mice and rabbits. Teratogenic effects of 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (oxepinac) were examined in mice and rabbits. Oxepinac was orally given to pregnant animals during the organogenesis period at 3, 30 and 90 mg/kg/day for mice, and at 3, 10 and 20 mg/kg/day for rabbits. It can be concluded that oxepinac has no teratogenic effect on fetuses in mice and rabbits. In addition, the medication of oxepinac to pregnant mice does not adversely affect the postnatal development of their pups.


[In vitro tests for the reduction of high norepinephrine, barbiturate and bromide concentrations in blood by hemofiltration (author's transl)]. In vitro tests have shown that a treatment of blood according to the principle of hemofiltration is suitable both for the normalisation of excessive norepinephrine plasma level, e.g. following severe burns, and also for the elimination of toxic quantities of barbiturate and bromide resulting from poisoning by sedatives.


[A multiple iteration program for determining global pharmacokinetic constants on a digital computer (author's transl)]. A program for determining pharmacokinetic constants on the basis of multiple iterations is described. After obtaining values for tmax, cmax and kel by means of graphs, the program calculates all important constants as well as the Bateman function between 0 and 24 h, adapted to the problem. Due to its simple handling the program is very reliable for the daily work of the kineticist.


The immunosuppressive activity of azathioprine in serum and cerebrospinal fluid. Azathioprine and its active metabolites can be detected in the cerebrospinal fluid (after i.v. injection). At a single dose of azathioprine maximum immunosuppressive activity occurs in the serum after 1 h and in the cerebrospinal fluid after about 4 h. Maximum immunosuppressive activity in human cerebrospinal fluid is about 12.5% of the equivalent serum level. A certain amount of time is needed for azathioprine and its metabolites to reach the cerebrospinal fluid where they remain for some time before passing into the serum, from where they are broken down. The findings are clinically important for the treatment of inflammatory nervous diseases, for example, multiple sclerosis, which are assumed to be of immunopathological origin.


The renal elimination of rifampicin as a function of the oral dose. A convenient way to assess relative bioavailability. A spectrophotometric method for the quantitative determination of rifampicin in urine is described and its specificity and precision are discussed. It is shown that the mean cumulative urinary elimination of rifampicin is reproducible when the same dose is administered twice in two different experiments to the same group of volunteers. The percentage of the amount eliminated increases with increasing dose. The renal elimination of apparent rifampicin can be used as a parameter for assessment of relative bioavailability of rifampicin from oral dosage forms of the same nominal strength if an appropriate number of volunteers is involved in the test.


Different tumours induced by benzo(a)pyrene and its 7,8-dihydrodiol injected into adult mouse salivary gland. A comparison has been made between the carcinogenic activities of benzo(a)pyrene and the proposed proximate carcinogen, benzo(a)pyrene 7,8-dihydrodiol, in the adult C57BL mouse submandibular salivary gland. In preliminary studies using a range of doses, the dihydrodiol was slightly less active than the parent hydrocarbon in this system. There was a difference in the type of tumour induced by the 2 compounds. Benzo(a)pyrene induced tumours of the salivary glands at the site of injection, whereas the dihydrodiol induced malignant lymphosarcomas, particularly of the thymus, which were often metastatic to other orgnas. Possible reasons for the different sites of action of the 2 compounds are discussed.


Studies on the anomalous thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures. Examination of the thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures by high-sensitivity scanning calorimetry has revealed that the phospholipid gel to liquid-crystalline phase transition consists of two components. One, a relatively sharp transition centered at 39.6-40.7 degrees C, exhibits a transition enthalpy change which decreases linearly with increasing cholesterol content, approaching zero at a cholesterol content of about 25 mol %. The other, a broad, lower intensity transition centered at approximately 41.5 degrees C for cholesterol concentrations of 20 mol %, displays an enthalpy change which is maximal at about 20-25 mol % cholesterol and which decreases as the cholesterol content decreases to zero or increases above 25 mol %. The origin of these two transitions is discussed in terms of a separation of these lipid mixtures into cholesterol-rich and cholesterol-poor domains.


Lateral diffusion of the phospholipid molecule in dipalmitoylphosphatidylcholine bilayers. An investigation using nuclear spin--lattice relaxation in the rotating frame. Measurements of the proton NMR spin--lattice relaxation time in the rotating frame (T 1rho) have permitted the explicit determination of the lateral diffusion coefficient of phospholipid molecules in the lamellar mesophase of dipalmitoylphosphatidylcholine at temperatures above the phase-transition temperature. The experimentally observed temperature and frequency dependence of T 1rho for the dipalmitoylphosphatidylcholine protons suggest that intermolecular dipole--dipole relaxation contributions are important. Proton T 1rho experiments involving dilution with deuterated dipalmitoylphosphatidylcholine support the premise that intermolecular dipolar interactions are significant and, concomitantly, that lateral diffusion is the motion modulating that interaction. The lateral diffusion coefficient is determined directly from the dependence of the rotating frame spin--lattice relaxation rate (1/T 1rho) on the strength of the applied radiofrequency field in the spin-locking experiment. A series of experiments with varying concentrations of dipalmitoylphosphatidylcholine in the lamellar mesophase indicates that the lateral diffusion coefficient varies as a function of phospholipid concentration.


Influence of membrane lipids on the photochemistry of bacteriorhodopsin in the purple membrane of Halobacterium halobium. Purple membrane fragments from Halobacterium halobium were reconstituted with the native lipids replaced by dipalmitoyl phosphatidylcholine and by egg lecithin. In parallel studies the temperature dependence of bacteriorhodopsin phototransient lifetime and absorption dichroism and of in situ lipid microviscosity were determined; the former two by, respectively, conventional and polarization flash photometry, and the latter by observation of emission depolarization of an embedded fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene. Discontinuities in lipid microviscosity profiles in native and egg lecithin purple membrane were reflected in both the photochemical cycle frequency and bacteriorhodopsin chromophore rotational mobility. The influence exerted by membrane-lipid viscosity appears to be a secondary effect, and points to the bacteriorhodopsin chromophoric group being situated in the protein interior.


Multiple phase equilibria in binary mixtures of phospholipids. Approximate phse diagrams describing lateral phase separations are given for binary mixtures of dimyristoyl phosphatidylcholine with dipalmitoyl phosphatidylcholine, distearoyl phosphatidycholine, and dipalmitoyl phosphatidylethanolamine. These diagrams are based in part on freeze-fracture electron microscopic data. These phase diagrams represent an improvement over previous studies in that both solid phses (Pbeta' and Lbeta') of the phosphatidylcholines are included. Further consideration is given to the problem of binary mixtures in which there are two Pbeta' phases that do not form a continuous range of solid solutions.


Deuterated phospholipids as nonperturbing components for Raman studies of biomembranes. The deuterated phospholipid, 1,2-dipalmitoyl-d62-phosphatidylcholine is shown by Raman spectroscopic measurements to be useful for obtaining information concerning phospholipid conformation in complex phospholipid and lipidprotein mixtures. The Raman bands of the deuterated phospholipid are assigned, and the sensitivity of these vibrational modes to conformational changes in the bilayer is demonstrated. Deuteration of the alkyl chains reveals the CH vibrations of the head group. A change in these bands is observed at the melting temperature and is assigned to alteration of the glycerol backbone conformation upon melting.