[Lymphokine production in the cell-mediated immune response (author's transl)].

In response to tuberculin, lymphocytes derived from BCG-sensitized guinea pigs elaborated soluble materials capable of inducing some reactions in vitro which correlated with the cell-mediated immune response in vivo. The lymphokine activity of these soluble materials was demonstrated by the following biological effects: macrophage migration inhibition, macrophage aggregation, cytotoxicity to HeLa cells and skin reaction.


[Development of Angiostrongylus cantonensis in the lung of Achatina fulica (author's transl)].

Twenty-four Achatina fulica from Pai-sha of the Pescardores Islands, where no Angiostrogylus cantonensis has been found in A. fulica(4), were inoculated with the first stage larvae of A cantonensis. One snail was killed every day after 24 days following inoculation. The lung of each snail was separated and examined for larvae under microscope. The same lung was then digested with pepsin. The larvae recovered after pepsin digestion were examined for more detailed morphology. This study confirmed that the first stage larvae of A. cantonensis passed through the respiratory pore to the lung of A. fulica and developed into infectious form (3rd stage larvae) in the lung. The second and third stage larvae were found in the lung on the 7th and 17th day respectively after inoculation. Worm capsules were found in the lung on the 12th day after inoculation and the size of capsule was in proportion to the duration of the infection.


External structures of all larval instars of five common Culex species in Taiwan.

The external structures of all larval instars of 5 different species of Culex were studied for the first time in Taiwan. Pictorial keys are provided for use to distinguish each species at any instar; one key is to larval instars of 5 common Culex species in Taiwan and the second, key to species of 5 common Culex species in Taiwan.


Effect of 1,5-dicaffeylquinic acid (cynarine) on cholesterol levels in serum and liver of acute ethanol-treated rats.

The effect of 1,5-dicaffeylquinic acid (Cynarine) on total cholesterol levels in serum and liver of acute ethanol-treated rats was studied. Male Wister rats were administered ethyl alcohol, 6 g/kg per day by gavage over three days. In rats treated with ethanol alone, the serum and hepatic cholesterol showed a significant rise of 44 and 75%, respectively. In rats receiving ethanol and Cynarine simultaneously, a distinct reduction of the serum and hepatic cholesterol levels was observed.


[Bilateral malignant lymphoblastic lymphoma of the female breast (author's transl)].

Primary bilateral malignant lymphoma of the breast was diagnosed in these women. All were of the lymphoblastic type of high malignancy. Two patients were pregnant and all died of generalised malignant lymphoma. Survival time between initial or early manifestation in the breast and death was two to four months.


Horner's syndrome in the horse: experimental induction and a case report.

The findings in 6 experimental and 1 natural case of Horner's Syndrome (HS) are presented. The experimental cases were induced by unilateral surgical section of the cervical sympathetic trunk in the middle third of the neck. The naturally occurring case was seen in a 17 year old gelding with a mediastinal tumour. The signs of HS in these horses included ptosis, miosis, enophthalmos, hemilateral sweating and temperature increase of the face and cranial cervical region on the affected side. The intensity of these signs was variable between and within animals. Miosis, enophthalmos and temperature difference were sometimes difficult to discern. Clinically the recognition of HS is important in the localization of lesions, and when accompanied by nasal haemorrhage is highly suggestive of guttural pouch mycosis.


[An autoclavable stainless steel isolator for small scale gnotobiotic experiments (author's transl)].

A lightweight stainless steel autoclavable pentagon isolator was designed for experiments using gnotobiotic mice. The chamber, 400 x 450 x 350 mm, has an entry port 200 mm in diameter at the back and a window at the ceiling. The globes and two filters were equipped at the front and each side, respectively. An inner stainless steel cap of the entry lock was sealed by a seamless silicone band. It was possible to ventilate this isolator by either free-flow or blower operation. After autoclaving the isolators 10 to 16 times for a year, none of them was repaired. Five mice can be kept in this isolator for about 1 month without supply of diet, water and wood shaving after the first setting.


Differential maternal retrieval of jaundiced versus non-jaundiced Gunn rat pups.

Gunn rat dams were tested for differential retrieval of their jaundiced versus non-jaundiced offspring in 2 experiments. In Experiment 1, in which testing took place every day from Day 1 to Day 8 postpartum, non-jaundiced pups were retrieved significantly faster than jaundiced pups. In Experiment 2, in which testing took place every other day from Day 1 to Day 15 and the pups were weighed each test day, the order of retrieval of the 4 gender/genotype (jaundiced vs non-jaundiced) classifications as found in the 1st experiment was replicated and the non-jaundiced pups tended to be retrieved faster. Heavier pups were retrieved significantly faster than lighter pups, indicating that weight or size may be a cue to differential retrieval.


K cell activity of normal and chronic lymphocytic leukaemia lymphocytes: association with lymphocytes bearing receptors for human C3b.

Blood lymphocytes of patients with chronic lymphocytic leukaemia (CLL) and of normal individuals were depleted of EAC3b- or EAC3d-rosette-forming cells (RFC), respectively and assayed for K-cell activity in a system measuring antibody-dependent-cell-mediated cytotoxicity (ADCC). K-cell activity was found to be associated with a cell population bearing receptors for C3b.


Immunological evaluation of 15 children with non-Hodgkin lymphoma.

In the present study, 15 children with non-Hodgkin lymphoma have been immunologically evaluated by the following parameters on peripheral blood (PB) lymphocytes: phytohemagglutinin responsiveness (PHA-r); non-immune rosette formation with sheep red blood cells (RF-L) as T-cell marker; presence of surface immunoglobulins (sIg-L) as B-cell marker; serum immunoglobulins levels (IgA, IgM, IgG). Our patients (pts) have been divided in two groups: the first one includes 10 children without PB involvement; the second one includes 5 pts with bone-marrow and PB invasion. From our data it appears that: 1) the majority of pts of the first group presented normal values of membrane markers; PHA-r was impaired in 4/8 pts; 2) in pts with PB invasion absolute number of B and "null" cells was always abnormal and PHA-r altered; 3) in the second group of pts, a "null" cell origin can be suggested by the high percentage and absolute number of cells without surface markers. In our opinion, the high incidence of "null" cells represents the most relevant question: whether they are cells deprived of specific markers, or endowed with markers not identifiable by our current techniques, remains to be established.


The significance of chromosomal findings for the differentiation between lymphoma and lymphoblastoid cell lines.

Cytogenetic studies have been performed from four Burkitt's lymphoma cell lines, one cell line obtained after successful xenotransplantation of a Burkitt's lymphoma cell line into athymic nude mice, and from ten lymphoblastoid cell lines (three derived from umbilical cord blood cells, one from acute myelogenous leukemia and six from Hodgkin's disease specimens). Our findings indicate the non-neoplastic nature of lymphoblastoid cell lines in spite of their high proliferative activity in vitro and their aneuploidy after long-term cultivation. In contrast, cell lines of Burkitt's lymphoma origin apparently are truly malignant lymphoma cells, characterized by aneuploidy and by the presence of a 14q+-marker chromosome even in the EBV-negative cell lines. The 14q+-marker chromosome, observed in Burkitt's lymphoma as well as in other malignant lymphomas, seems to be related to neoplasia, independent on the presence of EBV. The significance of the aneuploidy for the differentiation between lymphoma and lymphoblastoid cell lines is discussed.


Internal knee lesions and medial discoid meniscus.

The authors stress the great importance of stability in the normal functioning of the knee and its resistance to injury. They describe a case of multiple internal lesions involving the anterior cruciate ligament, the medial collateral ligament and the lateral meniscus sustained in a knee already affected by a discoid medial meniscus. These lesions were caused by a relatively slight injury and the knee for some time over reacted to the slightest stress. Operation revealed the existance of a discoid medial meniscus and in the view of the authors this was the cause both of the knee's instability and previous episodes as well as the final severe traumatic syndrome revealed at operation. Discoid medial meniscus is extremely rare. Smillie's classification into three groups and the various pathogenetic hypotheses are discussed. The authors analyse the relation between knee instability and meniscal malformation and conclude that discoid medial meniscus plays a primary role in rendering the joint highly vulnerable.


Psychological factors involved in request for elective abortion.

In order to understand the increasing numbers of women who are requesting a repeat elective abortion, 13 First Abortion and 13 Repeat Abortion patients were interviewed. There were no significant differences between the two groups. It was found that the failure of contraception was not because the women did not have access to adequate contraception. There was evidence of underlying psychological conflicts, sometimes in one and even both sexual partners. In 9 of the 26 patients there was material clearly suggesting that the women had an underlying conflictual wish to become pregnant. The data also suggests that many of the male partners had a strong wish to father a child. All of these situations suggest the need for adequate counselling.


Tardive dyskinesia: characterization and prevalence in a statewide system.

The prevalence of tardive dyskinesia in a state-wide mental hospital system was assessed using a new quantitative rating scale and related to demographic, medication, and medical history variables. Twenty-six percent of patients had definite signs of tardive dyskinesia, about 12% moderately severe dyskinesia, and 40% exhibited at least some minimal symptoms. Tardive dyskinesia significantly increased with age, and females had a slightly but significantly greater prevalence rate than males. There was no difference in dyskinesia prevalence between patients on or off neuroleptics at time of rating, but patients on multiple neuroleptic drugs had higher prevalence of moderately severe dyskinesia.


Affective disorder in adolescence: issues in misdiagnosis.

This case report describes a young adolescent female with bipolar manic-depressive illness, (MDI), whose behavioral symptomatology was originally attributed to non-affective forms of psychopathology. We review her entire clinical course to date and elucidate several factors that may account for diagnostic error.


Neuromyopathy in malignant hyperthermia.

A 31-year old male developed malignant hyperthermia (MH) during the initial minutes of Halothane induction. CPK rose to 6120 U/ml and decreased to normal levels as the patient became afebrile over a 10 day period of cooling measures and metabolic management. Muscle weakness, predominantly proximal and depressed deep tendon reflexes were found upon examination during convalescence. Muscle biopsy showed neurogenic changes characterized by fiber type grouping and targetoid fibers. CPK was elevated in one of the patient's children. This case supports the view of underlying hereditary neuromyopathy in MH.


Propoxyphene and Phencyclidine (PCP) use in adolescents.

Trained interviewers utilized a structured research instrument to analyze drug use patterns, personal and familial psychiatric problems, and social backgrounds of a consecutive series of 355 adolescent referred by courts to alcohol counselling and education centers in King County. Within this sample, 4% of the subjects used propoxyphene alone, 16% reported use of phencyclidine (PCP) alone, and 6% reported abuse of both substances. The data consistently reveals that the use of one of these more unusual substances is likely to occur in people with more antisocial, drug, and alcohol problems. Use of both drugs was associated with the most pervasive antisocial history, with over one-third of these subjects fulfilling strict criteria for the antisocial personality. The treatment and prognostic implications of these findings are discussed.


Pathophysiologic mechanisms of hydrocephalus.

Hydrocephalus is caused by a disequilibrium of forces at the ventricular-cerebral interface and may be progressive either due to a continued disequilibrium of forces or due to continued progressive periventricular ischemic injury. Treatment is indicated in all patients with progressive neurological deficit associated with progressive ventricular enlargement. Whenever possible, treatment should be directed toward the cause of the hydrocephalus (e.g., removal of tumors obstructing CSF flow) or the specifically abnormal force vector (e.g., shunting for increased intraventricular pulse waves due to an ectatic basilar artery). When it is not possible to treat the cause or the specifically abnormal force vector, treatment should be guided by the basic mechanisms--reduction of the intraventricular force (Fo), augmentation of the inward brain force (Fi), and improvement of nutrition and oxygenation of ischemic periventricular tissue.


Hoffman's syndrome: a peculiar case.

The Authors describe the case of a 50-yr-old woman with painful muscular cramps and high muscular enzymes level secondary to adult-onset myxedema, and where no histological and ultrastructural muscle alterations could be detected, probably owing to the early observation of the patient.


Rampant dental caries in the treatment of depression.

Dental Caries are an uncommon, but significant side effect of the tricyclic antidepressants and other anticholinergic psychoactive drugs. The authors trace the etiological aspects of this syndrome including the effects of depression and antidepressant medication on salivary properties. A typical clinical presentation of the syndrome is described and the side effect profiles of the various tricyclic antidepressants are compared. With this clinical background guidelines for the management of dry mouth are presented, emphasizing the importance of technical skill, safety and continuity of care.


Hemiatrophy of the tongue: a rare complication of the hemiplegic migraine.

A rare case of a patient with complicated migraine is presented. The patient had hemiatrophy of the tongue as a residual of a migraine episode. This cleared after several months. The paper goes on to trace the history of complicated migraine and the rather unusual complication of hemiatrophy of the tongue.


Pilot study of d-penicillamine, vitamins and minerals in multiple sclerosis.

A pilot study of the effect of D-penicillamine in multiple sclerosis (MS) was undertaken because of D-penicillamine's activity against RNA neurotropic viruses, because it is effective against the auto-immune disease, rheumatoid arthritis, and because both viruses and autoimmunity have been implicated in multiple sclerosis. We have treated 16 patients with advanced MS, nine on full doses (2-2.25 grams/day) and seven whose treatment was permanently stopped for reasons other than adverse reactions. There has been some improvement in most of those whose treatment was not withdrawn, and no change or deterioration in those not continued on the therapeutic regimen. Despite use of a high dosage regimen, such as has evoked intolerable side effects in a high percentage of patients with rheumatoid arthritis, we have experienced few side effects in a total of 48 patients suffering from diseases with auto-immune components, a finding we speculate is due to replacement of nutrients inactivated or removed by D-penicillamine, and to supplementation with selected nutrients.


Psychiatry on death row.

The authors present the personal experiences of an attending physician in a Death Row in Ceylon (Sri-Lanka). Aspects of the execution scenario are presented and discussed with its implications for the protagonists: the condemned, witnesses, standers-by, authorities and society-at large.


Drug monitoring at an Australia depot phenothiazine clinic.

Three aspects of treatment with injectable neuroleptics, are presented. An individualized approach to the dosage of Fluphenazine decanoate must be practiced in conjunction with, and taking into account the time spent in treatment and the sex and age variables reported. Our flexible approach to the interval between injections, indicated a large group could be maintained at intervals of 5 to 8 weeks. Complex and challenging problems can be found with antiparkinsonian drugs; 30% of nearly 400 outpatients still require these drugs.


The role of physical restraint in the treatment of psychiatric illness.

Although physical restraint is a widely used and possibly hazardous form of treatment, few guidelines for its use appear in the recent psychiatric literature. An approach is described in which physical restraint is considered to be a specific therapeutic technique with definable indications, "dosages", contra-indications, and side effects. A method of initiating and terminating this treatment modality is presented and the indications for its use are discussed. These include the presence of violent behavior during a psychotic illness; the presence of agitation or confusion when the use of antipsychotic medication is limited by physical illness; the presence of severe psychotic symptoms in conjunction with severely regressed, socially aversive behavior; the need to reduce excessive external stimuli; and the request for restraint by the patient. Possible side effects and contra-indications are also discussed and criteria for evaluating the duration and effectiveness of the treatment are proposed.


Cancer pathomimicry: a report of three cases.

Three cases of alleged and feigned cancer are presented. The diagnostic and management problems presented are discussed through a review of the literature of feigned illness. This ranges across a spectrum from benign use of feigned or alleged symptoms, malingering, conversion reactions and hysterical manifestations to the severe and flamboyant clinical presentation of the Munchausen Syndrome. The cases presented mainly fit the criterion for malingering (conscious prevarication and simulation), although some elements of the Munchausen dynamics were present in two of the three. Also noteworthy was the fact that the "cancers" were presented to administration and lay people as an initial communication. The psychiatric consultation was with the lay people initially and the events of each episode were reconstructed through multiple sources of information including clinical interviews in two of the cases.


Hypothyroidism and psychosis: a case illustration of the diagnostic dilemma in psychiatry.

A case of a forty-eight year old woman with myxedema and acute psychosis is reported to illustrate the difficulties of diagnosis in psychiatry. A specific focus is placed on the problem of differentiating organic from functional illness. Several guidelines are offered to aid the clinician with the problem of diagnosis.


Negative treatment responses in psychiatry.

Powerful disagreements about the helping relationship are often expressed by clinical worsening of the patient and by defensive reactions of the doctor. Typical presenting patterns are the patient who wants "more" from his doctor, or who feels the doctor expects "too much" of him. Resolution of these relationship issues depends on empathic understanding and clarification of the patient's feelings plus small, symbolic, nonverbal gratifications of the patient's felt needs. After resolution of the relationship impasse, specific therapies are more likely to be effective.


Peroneal palsy in depression.

In the psychiatric patient cross leg palsy can be a subtle but significant problem. The patient, rendered inactive by a depressive illness, who has lost weight, whose activities include much sitting, or who has a disease that may predispose to a neuropathy, should be observed closely for this preventable and treatable problem.


Management of disturbed patients: an alternative to the use of mechanical restraints.

This article briefly outlines some of the causes for violence and describes step by step guidelines to the management of disturbed behaviour in psychiatric patients including how the episode of violence can be dealt with by using a well planned approach, the effective use of medication in the management of acute crises and the actual physical handling of the patient. Recommendations are made regarding the need for the proper education of staff of all disciplines about the causes, prevention and management of such behaviour. The need for a well planned hospital wide policy as well as a treatment plan for each patient which contains contingencies for the management of those who are potentially violent is discussed with emphasis on the need for a thorough discussion following such episodes. The dangers and abuses of mechanical restraints are outlined.


Neuropsychological test performance as a function of the duration of MS-related symptomatology.

Thirty-six patients with definite diagnoses of multiple sclerosis received an extensive battery of neuropsychological tests. The MS patients were grouped in triads, and the members of each triad were matched on the basis of their sex, age at time of experiencing their first MS-related symptom, and education. One member of each triad was assigned to each of three experimental groups on the basis of the number of years they had complained of MS-related symptoms (i.e., one to five, six to ten, or greater than ten years). Data analyses yielded a limited number of significant findings. Differences on measures of verbal intelligence and reading skills were suggested as more probably reflecting a tendency for the "older" MS patients to have had more formal education, than being a true consequence of the disease process. Only a measure of simple tactile perception skills significantly delineated the experimental groups in a manner consistent with clinical observation of MS deterioration.


Folic acid, mental function, and dietary habits.

The combination of biochemical theory, case studies, and patient population surveys suggests that the water soluble vitamin, folic acid, is relevant to mental functions. Several studies demonstrate a clinical correlation between folate deficiency and psychiatric hospitalization. The role of dietary deficiency to these observations has needed further examination. After reviewing the serum folate values of 269 psychiatric hospital admissions, the incidence of serum folates below 5.9 ng./ml. was found to be greater than a control group. A dietary rating for all admissions revealed a high frequency of deficiency in all patients with no greater prevalence among the low folate group. These observations agree that psychiatric patients are more likely to have low serum folate values, and suggest that poor diet does not explain the increased likelihood.


Sexual involvement with patients.

Three cases of sexual activity between patients and staff members were presented and determinants and consequences of this type of acting out behavior were discussed. Patients sexual behavior was in part motivated by a need to avoid feelings of loneliness and anxiety and a consequence of the sexual behavior was the recurrence of symptoms and behaviors noted upon admission. The staff members were noted to become more self preoccupied and less involved with both staff and patients following the sexual behavior. The role of the ward psychiatrist in preventing such patient staff interactions includes his taking responsibility for educational and supervisory needs of the staff, his being involved in the creation and maintenance of the ward's moral code and his awareness of group and organizational factors that may impede open staff communications.


The family history of mental illness and welfare dependence.

During the year 1975 clinical interviews are obtained on all patients referred to the East Providence Community Mental Health Clinic for diagnosis and treatment. Data was obtained as to the presence or absence of a family history of similar mental illness. A hypothesis was tested that those patients with a family history of mental illness similar to that of the patient, were more likely to be welfare dependent. Correlations between patients with a positive family history of either schizophrenia or depression and welfare dependence were highly significant within social class 5 (unskilled laborers). However, these same correlations were negative within social class 4 (working class). The positive correlations suggest the possibility that the major mental illnesses are important factors in the need for welfare.


The patient-therapist relationship in crisis intervention.

A crisis situation, because it engenders feelings of helplessness, promotes regression in the patient and thus makes the patient susceptible to the rapid formation of an intense positive relationship between himself and the therapist. While this type of patient-therapist relationship is useful for the treatment, it requires constant monitoring on the part of the therapist lest dependency and regression be furthered. Cases are presented which illustrate some of the problems that may be encountered as a result of the patient's feelings about the therapist, and techniques for avoiding these problems are discussed.


Hypothalamic atrophy.

A patient, who has been followed for thirteen years, developed the first symptoms of progressive hypothalamic atrophy at the age of 39. The diagnosis was confirmed by pneumoencephalography five years after onset. Hypothalamic dysfunction was manifested clinically by loss of libido, impotence, obesity, polydypsia, somnolence, and rage attacks. Assessment of endocrinologic function demonstrated low serum levels of testosterone, FSH, and LH, a diabetic glucose tolerance curve, decreased basal and hypoglycemic stimulated levels of HGH, and progressively increasing levels of serum prolactin. Repeated pneumoencephalography revealed an initial, and then progressive, enlargement of the third ventricle which was later associated with generalized, but proportionately less severe, atrophy of the cerebellum and cerebral hemispheres. Analysis of the physiologic and endocrinologic mechanisms underlying these abnormalities suggests diffuse hypothalamic damage, especially in the ventromedial area. The decreased somnolence and increased libido and potency which accompanied therapy with levodopa suggest damage to dopaminergic and noradrenergic pathways. Slowly progressive hypothalamic atrophy, confirmed by pneumoencephalography, but without specific etiology, has not been reported previously. This article describes such a patient followed over thirteen years, and the efficacy of therapy with levodopa in ameliorating certain aspects of his disease.


A long term comparative trial of penfluridol and fluphenazine decanoate in schizophrenic outpatients.

Penfluridol, a diphenylbutylpiperidene derivative, is a new long acting neuroleptic, administered orally, once weekly. It is marketed in several European countries and has been used successfully in the treatment of various acute psychoses, for severely ill chronic schizophrenic patients, and as maintenance therapy for chronic schizophrenic patients. The present study was designed to compare, in a double-blind fashion, the efficacy of penfluridol and fluphenazine decanoate in the maintenance therapy of schizophrenic outpatients.


Isolation and properties of thyroglobulin-related 4S protein in the soluble fraction of thyroid tissue.

A 4S protein which is thyroglobulin-related and which is immunologically distinguished from unusually iodinated albumin-like proteins or impaired substances of thyroglobulin synthesis, was found in the thyroid-soluble fraction even in the normal gland, though in minute amounts. In the present study, purification and characterization of the substance has been carried out using human and hog thyroid glands. This protein contains some of the immunospecific determinants of thyroglobulin, although the amino acid composition of the protein differs from that of thyroglobulin. The 4S protein has a molecular weight of about 58,500 as determined by the sedimentation equilibrium method. Interestingly, the present 4S protein is eluted just in front of, or together with, thyroglobulin by gradient elution chromatography on a DEAE-cellulose column, and it is precipitated with thyroglobulin at 1.9 M ammonium sulfate. Therefore, it was concluded that a molecular-sieving process is necessary for the purification of thyroglobulin, in addition to a complex procedure which consists of ammonium sulfate fractionation and DEAE-cellulose chromatography.


Nutritional status of lacto-ovo vegetarian Trappist monks.

The nutritional status of members of a lacto-ovo vegetarian Trappist community was studied. Body weights and heights were normal. An analysis of four weeks' menus showed that, for the most part, sufficient nutrients were provided. A 24-hr. dietary recall revealed that a number of the subjects had low intakes of some nutrients, particularly the B-vitamins and calcium, iron, magnesium, and zinc. Improvement in the nutritional intakes and resulting nutritional status of the men must rely on an availability of accurate educational materials and each individual's determination to gain the knowledge needed to make a wiser selection of food.


Mineral content of dairy products. I. Milk and milk products.

Sixteen kinds of dairy products were analyzed for five major minerals and four trace minerals. Commercial samples of fluid milk, cream, concentrated milks, cultured products, butter, and frozen desserts were also analyzed for fat, solids, protein, and minerals. Calcium, magnesium, sodium, and potassium were determined by atomic absorption, and phosphorus was determined colorimetrically. Flameless atomic absorption was used to determine iron, zinc, copper, and manganese. The data generally agreed with most recently published values. However, for the trace minerals, the data differed widely in some instances. Manufacturing practices and added ingredients produced considerable variations in mineral content of market samples. These variations, however, could be limited by selection of products, so that they would not preclude the use of dairy products in diets in which mineral composition must be controlled. The coefficients of variation, which indicate the variability that can be expected for each product, generally were high for sherbet and ice milk and low for low-fat milk and skim milk.


Enzootic and epizootic Venezuelan equine encephalomyelitis virus in horses infected by peripheral and intrathecal routes.

Forty-five horses were infected peripherally or intrathecally with enzootic or epizootic strains of Venezuelan equine encephalomyelitis (VEE) virus. Low titers of virus appeared in cerebrospinal fluid (CSF) after peripheral inoculation of enzootic or epizootic VEE virus strains. Intrathecal infection with either epizootic or enzootic VEE virus produced higher titers of virus in CSF than did peripheral infection. In contrast to peripheral infections with enzootic strains, intrathecal infections with these strains caused death. The animals that died had widespread histopathologic changes and large amounts of virus in brain tissue. The attenuated VEE virus vaccine strain, TC-83, also multiplied in the brain of horses inoculated intrathecally but caused no clinical disease and little histopathologic damage.


Surgical results of orbital decompression for malignant exophthalmos.

In summary, we have presented the epidemiology, pathology, clinical classes, diagnostic techniques and surgical techniques employed, and the results in 220 patients who have undergone transantral orbital decompression for malignant exophthalmos. Reduction of proptosis up to 12 mm has been obtained. In 80 per cent of the patients the eyes were balanced within 1 mm. Complications have been minimal. We feel that this procedure has proven its efficacy in the treatment of malignant exophthalmos. In most cases it enables the preservation or improvement of vision and arrests the progressive extraocular muscle imbalance. The importance of close cooperation between otolaryngologist, endocrinologist and ophthalmologist cannot be overemphasized in the management of this disorder.


Measurement of metabolites in single preimplantation embryos; a new means to study metabolic control in early embryos.

Methods are described for preparing and analyzing single preimplantation mouse embryos for a variety of metabolites and cofactors (glucose-6-P, fructose-6-P, fructose-1,6-bisphosphate, ATP, AMP, Pi, citrate, isocitrate, alpha-ketoglutarate, and malate). Oil-well and enzymatic cycling techniques are combined to provide the sensitivity needed to measure the amounts present (10(-12) to 1o(-15) moles). After experimental treatment, embryos are collected on glass slides and freeze-dried. They can then be stored indefinitely under vacuum at -25 degrees C without deterioration. With these procedures, the embryos were collected at successive stages of development and subjected to starvation and refeeding with glucose, pyruvate or both. The results confirm the existence of a block at early stages at the P-fructokinase step. This may be due to inhibition by the very high citrate levels present. The data suggest that glycolysis is turned on late in preimplantation development by the rise in fructose-6-P, a deinhibitor of P-fructokinase. In the citrate cycle, no step between citrate and alpha-ketoglutarate is rate-limiting, but a step between alpha-ketaglutarate and malate appears to impede the flux at early embryonic stages.


Transient steatorrhea following episodes of mild diarrhea in early infancy.

Fecal fat excretion was studied after a mild episode of diarrhea in eight infants for whom adequate control data were available. Mean age of onset of diarrhea was 28 days. Duration of the episode, defined as the number of days until the infant was again feeding and libitum, averaged 5.1 days. Balance studies were carried out 3 to 13 days later. Mean fecal fat excretion rose from a prediarrhea value of 2.9 +/- 1.4 gm/day to 8.7 +/- 3.1 gm/day following diarrhea (P less than 0.001). Restudy of five infants one month later showed persistent steatorrhea in one. Mild transient steatorrhea may follow mild diarrhea in infancy and should be considered in infants who are slow to gain weight subsequent to an episode of diarrhea.


Complete heart block with hyperthyroidism.

Thyrotoxicosis developed in a patient while receiving thyroid hormone therapy for clinical hypothyroidism. The development of second-degree heart block of Mobitz type 1 variety was followed by third- and then first-degree heart block. We conclude that the varying degrees of heart block were secondary to hyperthyroxinemia caused by Graves' disease and exogenous thyroid hormone.


[Nasal and pharyngeal mucous membrane in workers of artistic weaving plants].

68 persons employed at the production of fabrics from wool and flax, have been subjected to otolaryngological examinations. Chronic atrophic catarrh of mucous membrane of nose and pharynx was found in all 8 persons employed in tapestry weaving mill and in 44 among 60 employees of a weaving mill operated manually. Atrophic changes occurred most frequently both in the nose and the pharynx, less frequently only in the nose, and the least frequently only in the pharynx. Chronic atrophic catarrh of upper respiratory tract mucous membrane was found to be more frequent among those with the length of employment above 5 years than those with shorter employment, though this difference was not statistically significant. No correlation was found between the occurrence of chronic catarrh of upper respiratory tract and hearing damage.


Correlation of sequential changes in serum thyroglobulin, triiodothyronine, and thyroxine in patients with Graves' disease and subacute thyroiditis.

Serum thyroglobulin (Tg), triiodothyronine (T3), and thyroxine (T4) concentrations were measured in sera from selected patients with hyperthyroidism due to Graves' disease and with subacute thyroiditis. In agreement with previous reports, the concentration of serum Tg was elevated in untreated hyperthyroidism due to Graves' disease, being 132 +/- 124 ng/ml (mean +/- SD) as opposed to 11 +/- 6.4 ng/ml in normal subjects. During treatment of hyperthyroidism with antithyroid drugs with or without iodide, reductions in thyroid hormone concentrations were not associated with a change in serum Tg. On the other hand, marked elevations in serum Tg to concentrations as high as 7000 ng/ml were observed within 24-48 hr after subtotal thyroidectomy or 131I treatment of patients with Graves' disease. These abrupt 10-50-fold increases in serum Tg were not associated with changes in serum T3 and T4. As previously demonstrated, patients with subacute thyroiditis may have elevated serum Tg concentrations that are not associated with elevations in serum T3 and T4. Serum Tg may remain elevated long after clinical and other biochemical mainfestations of this disease have disappeared. These data suggest that the disruption in thyroid function in patients with subacute thyroiditis may persist in a subclinical form for longer periods than previously suspected. Serum Tg appears to be a sensitive indicator of acute thyroidal damage due to surgical, radiation, or inflammatory trauma. The absence of parallel changes in serum Tg, T3, and T4 indicates that release of these thyroidal components can occur by different mechanisms and that nonthyroid tissues cannot efficiently generate T3 and T4 from circulating Tg. Accordingly, local or systemic stimulation of thyroidal Tg hydrolysis may be involved in the generation of hyperthyroidism sometimes seen in patients with subacute thyroiditis.


[Surface properties of cerebrospinal fluid cells following intrathecal methotrexate treatment].

Authors first in the literature described the surface profile of lymphocytes, plasma cells, phagocytes and malignant lymphoblasts of the liquor after intrathecal Methorexat therapy (i.thec.MTX). After prolonged treatment with MTX the mentioned cells were examined by SEM. The surface of the plasma cells and storage cells was found to be normal. Various stages of the phagocytosis could be observed. On the other hand the majority of lymphoblasts of leukaemic origin after the first administration of i.thec.MTX revealed damaged cell surfaces.


Neurovisceral storage disorder simulating Niemann-Pick disease. A new form of oligosaccharidosis?

Two sisters are described with demonstrable splenomegaly already from infancy and, after the age of 2--4 years, signs of slowly progressive encephalophy, vacuolated lymphocytes in the peripheral blood, and peculiar foam cells in the bone marrow aspirates. The died at 7 3/4 and 6 1/2 years. Widely  spread in the brain, the nerve cell bodies were found to show extensive ballooning. It was most striking in the brain stem and spinal cord, while cerebellar structures were remarkably well preserved. The cytoplasm of the ballooned nerve cells was filled with finely granular storage material stainable as a readily soluble glycolipid. The spleen, liver and intestinal wall contained numerous foamy PAS-positive macrophages. Chemical assays showed a ten-fold increase of lactosylceramide and a modest one of minor gangliosides brain cortex. No accumulation sphingomyelin could be revealed, and the sphingomyelinase activity was found to be normal. The ganglioside GM1 beta-galactosidase activity of leucocytes was reduced to 20--25% of normal, which indicated a disturbance of the glycosaminoglycan metabolism. The tissue content of glycosaminoglycans was, however, normal, but an accumulation of lactose was demonstrated in the spleen. It is postulated that the primary enzymic defect is a disturbance of a lysosomal beta-galactosidase with a substrate specificity for lactose and other oligosaccharides with a terminal beta-galactosidic linkage.


[Acquired aphasia with electroencephalographic manifestation in children (author's transl)].

The paper presents the case of a 5 year old boy with the syndrome of gradually developing aphasia, primarily receptive, associated with electroencephalographic abnormalities and behavioral problems. The aphasia developed over a period of 1 1/2 years and was primarily concerned with receptive language. At its peak there was a complete loss of language which coincided with almost continuous spike-wave discharges in EEG as did behavioral problems (hyperactivity and aggressiveness). No seizures occured. With anticonvulsive medication the abnormal EEG-activity diappeared within a 3 week period. Language improvement only began slowly 2 months later. Complete restitution of language was attained 1 year after the total loss of language. As the language improved, the behavior normalized. Various specialist were engaged in the diagnosis of the case and their procedures are described. The cause of this syndrome remains unknown. Similar cases (often with convulsive disorder) reported in literature are discussed and presented in a table.


Physical properties and biochemistry of lung surfactant following vagotomy.

Surface tension and the biochemical composition of lung washings were studied in rats 24 h after bilateral cervical vagotomy. A significant decrease in body weight, rate of breathing, stability and hysteresis shape indexes and hysteresis loop areas were noted. The gamma max, gamma min, gamma stat, indexes of compressibility, the number of cells and the protein content of washings were significantly increased. There were only minor changes in the absolute amount of phospholipids but their relative rate was significantly lower. Interstitial lung edema and early bronchopneumonia were confirmed histologically.


Effect of transfer factor and zoster immunoglobulin in patients with varicella-zoster infection and malignancy.

Immunotherapy was given to 13 patients suffering from lymphoproliferative diseases complicated by varicella-zoster (VZ) infection. Five patients received transfer factor (TF) only, 6 received TF and zoster immunoglobulin (ZIG), and 2 received ZIG only. ZIG did not seem to alter the course of the infection. Cessation of vesicle formation and initiation of crust formation took place within 1 day after the first injection of TF in 5 patients with a localized zoster. In 4 patients suffering from an early dissemination of VZ infection, cessation of vesicle formation took place within 1 day (1 patient), 2 days (1 patient), 3 days (1 patient) or 4 days (1 patient) after the first injection of TF. An increase in serum interferon was observed in 4 of 9 patients who received TF, while no increase in serum interferon was observed in the control groups. Administration of a high-titer ZIG preparation did not seem to depress the humoral antibody response when combined with TF therapy. Therapy with TF in combination with ZIG seemed to have a beneficial effect in patients with malignancy when administered early in the acute VZ infection.


Contact angle and surface tension in studies of lung surfactant.

The contact angle (theta) was determined in combination with surface tension measured in a Langmuiur-Willhelmy surface tension balance. Correction of the surface tension by the contact angle factor (1/cos theta) was tried on the monolayer curve of dipalmitoyl phosphatidyl choline (DPPC) and total lipid extracts from the bovine lung surfactant material (TLE). The contact angle was observed with an optical apparatus called a Contangulometer and pictures taken discontinuously, and was determined by drawing tangents at the peak of a junction between the water mensicus and a glass plate. The contact angle was about 15 degrees, and had a narrow range of variation until the surface tension became very low, less than 5 dynes/cm, and then the contact angle jumped to almost 90 degrees both in DPPC and in TLE. It is concluded that the directly recorded surface tension curve underestimates the value by about 3-4% and that when the surface tension becomes very low, less than 5 dynes/cm, the value is no longer valid because the contact angle becomes nearly 90 degrees.


[Surgery of patients with toxic goiter].

Some peculiarities of the toxic goiter found in patients in the republic of Afghanistan are considered. The results of surgical treatment of 68 cases are set forth. The advantage of beta-blockators over the antithyroid drugs for the preoperative management of these cases is shown.


[Lymphocytic infiltrations in normal and pathological thyroid glands (so-called focal lymphocytic thyroiditis) (author's transl)].

A series of 1004 goitres removed surgically before (1959) and after (1970, 1975) the introduction of the iodine prophylaxis reveals an impressive increase in lymphocytic infiltration of the thyroid gland parenchyma. So-called focal lymphocytic thyroiditis is closely associated with the functional state of the organ. Furthermore, there is an increase in focal thyroiditis, especially in younger persons, after the introduction of iodine prophylaxis. Autoantibodies or clinical signs of inflammation were not found in these cases. Focal lymphocytic thyroiditis is seen as the expression of a regulatory function of the immunological system over the thyroid gland.


[Clinical aspects, diagnosis and therapy of food hypersensitivity].

Foodstuff allergens may cause, either ingested, inhaled, locally or systemically, a varied pathology related particularily to the skin, the respiratory and the gastrointestinal tract. Due to the bewildering multitude of symptoms and the lack of reliable methodology for the detection of the allergens, no diagnosis is reached frequently. None of the available test methods (not even new in vitro tests such as RAST) can replace a thorough medical history. Between 1970 and 1975, we have ascertained 63 cases of foodstuff allergy in our clinic in Zürich. Many of them presented as bronchial asthma, allergic rhinitis, urticaria and Quinckeedema. Celery, potatoes, milk, egg-white, cheese and cereals were most frequently encountered as allergens. The only wholly effective therapeutic procedure consists in eliminating the allergenfrom food, a measure whose practical realization may prove to be quite difficult. Some results with oral hyposensibilisation are presented.


[Investigation of the relationship of the mucilaginous substances of linseed to genotype and source (author's transl)].

1. The content of mucilaginous substances, respectively the capacity to swell is primarily a characteristic specific for the variety. 2. Ecologically very different growth locations also have a marked influence, so that appreciable quality differences depending on origin mayorise. 3. From the positive correlation between sedimentation value and alcohol soluble fraction of protein it can be concluded that the swelling capability is not only influenced by the soluble pentosans but also by the protein composition.


Simplified fluorimetric methods for determination of vitamin B6 in food materials.

A simple fluorimetric method for the determination of vitamin B6 in food materials is proposed, enabling total vitamin B6 to be determined after the chromatographic removal of interfering substances on Dowex 50 WX 8 columns. Pyridoxol, pyridoxal and pyridoxamine are transferred into the highly fluorescent lactone of 4-pyridoxic acid. The method is specific and agrees well with the microbilogical assay. Three or four determinations can be performed in eight hours.


The accuracy of clinical applanation tonometry.

The differences between two careful applanation tonometries performed by one and by two observers, respectively, were compared. Two measurements by one observer differed by 2 mmHg or more in 8% of the pairs of measurements and by 3 mmHg or more in 2% of the pairs. One tonometry each by two observers differed by 2 mmHg or more 40% of the pairs of measurement and by 3 mmHg or more in 17% of the pairs. There was no dependence on the intraocular pressure. Possible reasons for the increase in variance are discussed.


Corneal thickness. II. Environmental and genetic factors.

In a material of 839 Greenland Eskimos with no corneal abnormalities, the variations of central corneal thickness (CT) were analysed from a genetic point of view. Environmental factors were suggested by a town-village difference in mean CT level (excess in town), by a higher CT level in families with an indoor occupation, and by a nearly significant husband-wife CT correlation. Using an age-sex-location-independent CT deviation score (CTDS) the family variations were studied in 86 families with two parents and one to seven children, and in 187 sibships with two to seven sibs. The first degree relationships showed a fairly high level of resemblance, which seems to indicate a major genetic influence on CT, with heritability estimates about 0.6--0.7. In men an association was found between CT and Caucasian admixture, which also suggested genetic factors. However, both findings call for reservation because of the socioeconomic environmental influence.


Cloxacillin distribution in the rabbit eye after intravenous injection.

Distribution of isotopically labelled and intravenously injected cloxacillin was studied in rabbit eye. The antibiotic concentration determined by liquid scintillation counting proved to be a reliable measure of the total antibiotic concentration when controlled by microbiological assay. In the rabbit eye after an intravenous injection of 50 mg/kg of cloxacillin sodium, longlasting antibiotic concentration regarded as therapeutic against penicillinase producing staphylococci was obtained in all vascularized ocular structures and in the cornea. The antibiotic present in the iris and ciliary body, and in the retina and choroid preparations, proved to be partly intravascular, whereas it penetrated better into the extravascular tissue compartment of the sclera and limbal area. Cloxacillin failed to achieve a therapeutic antibiotic concentration in the vitreous body and in the lens. Administration of probenecid had an enhancing effect on ocular cloxacillin concentration allowing improved drug diffusion into the eye by means of an elevated plasma concentration. No specific ocular effect of probenecid was noticed. Therapeutic concentration of cloxacillin in the aqueous humour, otherwise barely achieved, was more satisfactorily obtained with a previous injection of probenecid.


A note on the pseudo-exfoliation fibrils.

Both transmission (TEM) and scanning electron microscopy (SEM) demonstrate that typical fibrils are the dominant feature of the pseudo-exfoliation (PE) material. The purpose of this work has been to examine whether the TEM and the SEM fibrils are identical, and to determine to which extent the morphology of the PE material is changed during the preparation for SEM, especially by the drying procedure. Specimens from lenses with PE, which had beforehand been prepared for and examined by SEM, were embedded, sectioned and examined by TEM. The results indicate that, as far as it can be seen by this method, the changes induced in the PE material by the drying procedure are not substanial. The TEM and the SEM fibrils are identical.


The ciliary body and the suspension of the lens in rabbits. A scanning electron microscopy study.

The ciliary body in rabbits is dominated by the ciliary processes, which number about 165. Most of them are straight, regularly spaced and uniformly shaped, and they have an even surface when seen at low magnification. They are separated by deep valleys with almost vertical sides. Anteriorly, the ciliary processes end abruptly, and about every second process leads into an iridial process which run radially along the posterior surface of the iris. At higher magnification, the individual cells can be seen to be demarcated by furrows, with a pattern which is specific for the different parts of the surfaces studied. The lens is suspended in innumerable zonular fibers, forming a rather thick mat. They attach in one continuous belt at the anterior end of the ciliary processes, and directly on the lens equator. The anatomy of this part the rabbit eye differs in many respects from that found in primates.


Experience with trepanotrabeculectomy.

The authors analysed the effect of 100 trepanotrabeculectomy operations performed in primary (79 cases), in congenital (16 cases) and in secondary (5 cases) types of glaucoma. The operation itself could normalize the intraocular pressure in 87% of the cases, in 8% the intraocular pressure was normalized by miotics after the operation. In 3% of the cases the pressure could not be controlled even by the additional application of miotics and in 2% of the cases the operation produced a hypotony. The intraoperative and postoperative complications were temporary and without definitive sequels. As the blebs were present in 76% of cases, the authors concluded that the drainage took place under the scleral and conjunctival flap. In the smaller group, the blebs were absent but the intraocular tension was normalized. In these cases it is supposed that Schlemm's canal represents the main route of drainage. According to the authors' experience, trapanotrabeculectomy represents an operation which is easy to perform, which can not cause severe operative or postoperative complications and which can achieve normalization of the intraocular pressure, either by itself or with miotics, in a high percentage of cases.


Effect of paracentesis on ocular cloxacillin concentration.

The effect of anterior chamber puncture on cloxacillin concentration in the rabbit eye after intravenous injection was studied using a radioactive tracer method. The enhancement in drug concentration caused by paracentesis was most immediate and significant in the iris-ciliary body preparation. It was soon followed by high cloxacillin concentration in the aqueous humour, which contributed to elevated cloxacillin levels in the cornea, lens and anterior vitreous body, when compared to normal material. Contrary to normal eyes, cloxacillin concentration in the cornea of the punctured eyes was higher than in the limbal area. The morphological changes occurring after paracentesis are discussed. The breakdown of the hydrodynamic equilibrium in the eye, suggested as the only change after paracentesis by Raviola (1974), cannot merely explain the cloxacillin concentration changes measured in the punctured eye.


The effect of 5-iodo-2'deoxyuridine (IDU) and dexamethasone on corneal wound healing in the rabbit.

Using lamellar keratectomy as a model, the effect of 5-iodo-2' deoxyuridine (IDU) and dexamethasone on epithelial regeneration and stromal wound healing in rabbits was studied. Under IDU medication, there was a dose-dependent delay in both epithelial and stromal regeneration of the cornea. This negative effect of IDU was considerably intensified by additional doses of dexamethasone. When IDU was used alone, regeneration in the wound was delayed by five days in comparison to the control eyes. When dexamethasone was added, the delay was prolonged to about 10 days. The results are discussed and compared with the available literature.


Accuracy of evoked potential refractometry using bar gratings.

We recorded cortical potentials evoked by phase-alternating square-wave gratings. Significant effects of varying the refractive power of the eye are obtained only at 5 cycles/degree (cy/deg) and above. The extrapolation to zero amplitude of the evoked response as a function of spatial frequency predicts the psychophysical visual acuity even for the myopic eye. As the sensitivity of meridional refraction using sufficiently fine bar gratings is better than 0.5 D it provides a suitable means for the measurement of astigmatism.


Conjunctival bleeding in Osler's disease with associated platelet dysfunction. A case report.

A patient with Osler's disease (hereditary haemorrhagic telangiectasia) was admitted to hospital because of obstinate, profuse conjuctival bleeding occurring without any known preceding rrauma. Extensive examination of the haemostatic mechanism revealed an impaired platelet function reflected in defective platelet aggregation by ADP, collagen adrenalin and defective clot retraction. This platelet dysfunction, whose association with conjunctival telangiectasia was hitherto unknown, impaired the patient's already deficient primary haemostasis following the vascular anomaly and apparently contributed to the severity of the bleeding which could only be checked surgically. The findings seem to warrant investigation of the platelet function in patients with Osler's disease. In the event of platelet dysfunction drugs, such as acetylsalicylic acid (aspirin), indomethacin, dextrans as well as transfusions with bank blood are contraindicated.


Tissue culture of the retinal pigment epithelial cells.

Pure culture of the retinal pigment epithelial (RPE) cells of the chick embryo was carried out and the morphological characteristics of each developmental stage were observed under light microscope and transmission and scanning electron microscopes. Immature cells had a few, short processes on the apical surface and a few melanin granules in the cytoplasm. However, mature cells had two types of processes on the apical surface, one being narrow and the other wide. Many melanin granules were diffusely dispersed in the cytoplasm and the cells were joined by a junctional complex near the apical portion. Beneath the cultured cells, basement membrane and collagen fibrils were evident and were apparently produced by the culture RPE cells. The structure of the cultured cells in the well-differentiated stage appeared to be the same as that of living cells.


Necrotizing myopathy as a remote effect of gastric cancer accompanied with Hashimoto's thyroiditis.

An autopsy case of a 74-year-old male who had shown clinically hypothyroidism due to chronic atrophic thyroiditis (Hashimoto's thyroiditis), and pathologically necrotizing myopathy as a remote effect of gastric cancer was reported. Morphological features of this necrotizing myopathy was those of carcinomatous myopathy rather than those of hypothyroid or diabetic myopathy. As for the pathogenesis of the necrotizing myopathy (as a Group IV of polymyositis of Walton and Adams), the malignancy might have played an important role as a trigger of the secondary immunological abnormality upon a pre-existing longstranding immune disorder of Hashimoto's thyroiditis. Pseudomembranous colitis, which was thought to be related to antibiotics. (Lincomycin), was also briefly discussed.


Determination of the vacant amount of high-affinity bilirubin binding site on serum albumin.

A principle for determination of the vacant amount of the high-affinity bilirubin binding site on serum albumin in the newborn is proposed: A small amount of monoacetyl-4,4'-diaminodiphenylsulphone (MADDS) is added to the serum sample and the equilibrium of binding of this substance is assessed by measuring the rate of dialysis into another volume of the same serum. It is shown that MADDS is bound selectively to the specific bilirubin site. Results obtained after addition of varying amounts of five drugs and of oleate are compared with those found by the peroxidase method. Good agreement is found although certain deviations are encountered, as expected in the case of allosteric affects. Free bilirubin concentrations can be calculated from the results.


Mammary tumour inhibition and subacute toxicity in rats of prednimustine and of its molecular components chlorambucil and prednisolone.

Prednimustine, a chlorambucil ester of pregnisolone, retarded growth of DMBA-induced mammary tumours in rats and reduced the number of tumours. A combination of chlorambucil and prednisolone (C + P) in the same proportion as in prednimustine, had similar effects, 8 and 26 mg per kg of the C + P combination being equipotnet to 16 and 64 mg per kg of prednimustine, respectively. The mortality figures suggested that prednimustine was considerably less toxic than equipotent doses of C + P. This toxicity difference was confirmed in a parallel investigation of the subacute toxicity in rats of prednimustine and C + P. This study showed that the mortality, reduction of lymphocytes and platelets, and bone marrow depression was much lower after pregnimustine than after equimolar amounts of the C + P combination. The results suggest that the low toxicity of prednimustine makes this drug a better cytostatic agent than the C + P combination treatment.


Time course of the effect of insulin on bovine mesenteric artery.

The time course for the effect of insulin on the bovine mesenteric artery, a medium sized artery with a high content of smooth muscle, was studied. The arteries were preincubated for varying times (0--180 min.) with and without insulin. The magnitude of the insulin effect, subsequently assayed on the accumulation of glucose carbon and the distribution of 3-0-methylglucose, was found to increase with the time of prior exposure to insulin, approaching a maximum after about 120 min. Insulin exposure also augmented its effect on the incorporation of leucine-14C into protein in a similar way. Preincubation without insulin had no appreciable influence on the magnitude of the insulin effect, indicating that the sensitivity to the hormone did not change with time. The threshold concentration for the effect of insulin on glucose-14C accumulation was 0.01 U/ml without preincubation and 0.001 U/ml after prior exposure to the hormone for 180 min. An action on protein synthesis may be involved in the increase in the magnitude of the insulin effect caused by prior exposure to insulin since no increase was found after inhibition of protein synthesis by puromycin.


Cardio-respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits.

The toxic effects of alpha-d-propoxyphene (P) and its primary metabolite alpha-d-norpropoxyphene (NP) were compared to intravenous infusions (100 min.) of equimolar doses of P and NP (80 micronmol/kg equivalent to 30 mg/kg P HCl) in conscious rabbits. During P infusion severe respiratory depression and convulsions were seen in all animals, and six of the nine animals died. During NP infusion, however, only minimal respiratory depression was seen and all the animals survived. Considerable prolongation of the QRS complex and cardiac arrhythmias like intermittent A-V block and ventricular extrasystoles were seen in the ECG during both P and NP infusion, while the arterial blood pressure was unchanged. In P injection experiments (6 mg/kg P HCl), ECG changes preceded reduction in respiratory rate and during NP infusion only minor changes were seen in arterial blood gases, demonstrating that the ECG changes produced by P and NP are independent of respiratory depression. The ECG changes were found to be similar to those reported in quinidine intoxication. The QRS prolongation was markedly correlated with plasma concentrations during and after P and NP infusion. The results of the present investigation favour the hypothesis that the contribution of NP to the toxicity of oral P overdosage in man is ascribed to its cardiotoxic action whereas P is responsible for the CNS toxicity (respiratory depression and convulsions) as well as cardiotoxicity.


In vivo inhibition of prostaglandin synthesis in rabbit kidney by non-steroidal anti-inflammatory drugs.

To define dose- and time-response properties for in vivo inhibition of renal prostaglandin (PG) synthesis, aspirin, diclofenac sodium, indomethacin and d-naproxen were injected intravenously in different doses to unanaesthetized rabbits. After 30 min. the animals were killed and the post mortem accumulation of PGE2 and PGF2alpha in the renal medulla was determined by mass fragmentography. In control animals, the accumulated levels of PGE2 and PGF2alpha in the medulla were 9.2+/-2.2 (S.D.) and 1.5+/-0.6 microgram/g, respectively. Dose-dependent inhibition was demonstrated with all the drugs. The ED95 was for aspirin 15 mg/kg, for diclofenac sodium 1.5 mg/kg, for indomethacin 1.5 mg/kg and for d-naproxen 5 mg/kg. The duration of inhibition was studied by radioimmunoassay in anaesthetized rabbits by following the urinary excretion of PGF2alpha and PGE2 after an intravenous injection of solvent or test drug in doses twice the ED95. For three hours following aspirin, diclofenac sodium, indomethacin and d-naproxen, the decreases in urinary excretion of PGF2alpha ranged from 64 to 88, 87 to 95, 64 to 90 and from 40 to 77 per cent of the control, respectively, and the decreases in PGE2 excretion were of similar magnitude. Together these results indicate that diclofenac sodium might be used as a long-lasting and potent alternative to indomethacin and aspirin in experimental studies on the renal PG system in vivo.


Some properties of Ca-binding microsomal subfractions isolated from rabbit colon muscle.

From a homogenate of rabbit colon smooth muscle a microsomal fraction was isolated, which was divided into subfractions by centrifugation on a discontinuous sucrose gradient. The Ca-binding properties of the subfractions were investigated under different conditions. In the presence of 0.35 mM ATP the Ca binding of the fractions amounted to 4--8 nmol/mg protein. The 35% fraction bound more Ca per mg protein than the 35--45% fraction. The Ca accumulation was comparatively higher both in the presence of 5 mM ATP and in the presence of 5 mM oxalate. The two fractions showed about the same sensitivity for oxalate. This substance stimulated the Ca uptake at 5 mM but not at lower concentrations. The amount and the rate of Ca binding were more dependent on variations in the exogenous ATP concentration in the 35% fraction than was the case for the 35--45% fraction. The Ca binding was completely inhibited by salyrgan when the microsomal fractions were pretreated with this agent. Sodium azide did not influence the Ca-binding capacity of the fractions. It is suggested that the microsomal subfractions of the rabbit colon muscle represent physiologically important parts of the Ca sequestering system of the muscle, since Ca binding takes place at Ca- and ATP-concentrations which are believed to be present in the myoplasm.


A pharmacokinetic evaluation of free and DNA-complexed adriamycin: a preliminary study in children with malignant disease.

The pharmacokinetics of adriamycin given as free and in DNA-complexed form was compared in six children with malignant disease. The two types of adriamycin were given to the same child at 3--4-week intervals, thereby excluding genetic variations when comparing the results. Plasma and urine were collected during and after the drug infusion, and the drug concentrations were measured by means of a sensitive fluorimetric procedure. The study shows that one obtains: 1. a much higher plasma concentration of adriamycin when it is given in the complexed form. 2. a lower urine excretion of adriamycin and fluorescent metabolites when adriamycin is administered as the DNA-complex.


Effects of different cyclophosphamide treatment schedules on collagen and collagenolytic activity in granulation tissue.

Cyclophosphamide was injected intraperitoneally into rats in doses of 6 or 10 mg/kg/day. The controls had daily intraperitoneal injections of physiological saline. After 14 days of treatment, granulation tissue was produced by subcutaneous implantation of viscose cellulose sponges. The treatment with cyclophosphamide and physiological saline was continued in different sequences for a further one or two 14-day periods. The rats were killed 14 or 28 days after the sponge implantation. Cyclophosphamide caused a decrease in body weight, in the number of leucocytes, in granuloma dry weight and in the granuloma content of free OH-proline while the water percentage increased. Ten mg/kg/day of cyclophosphamide had a more pronounced effect than 6 mg/kg/day. The results are consistent with an inhibitory effect of cyclophosphamide on granuloma formation and on the degradation of collagen. Accordingly, measurements of collagenolytic activity in granulation tissue after culture in vitro suggested an inhibition of collagenolysis after cyclophosphamide treatment. No effect of pretreatment was observed, and the effect of cyclophosphamide was independent of whether cyclophosphamide was given during the early or late phase of granulation tissue production.


Pharmacokinetics of theophylline in ten elderly patients.

The two-compartment pharmacokinetics of theophylline in ten hospitalized elderly patients with apparently normal renal, hepatic and cardiopulmonary functions was investigated after intravenous administration of the drug. Nine patients suffered from slight hemiparesis and one from Parkinson's disease. Biological theophylline half-lives of 5.4--9.0 hours and plasma clearence values of 28--42 ml kg-1hr-1 were found. The apparent volumes of distribution during the beta-phase, Vdbeta, were 0.33--0.43 1 kg-1. It is concluded that a therapeutic concentration of about 10 microgram theophylline per ml serum could be established in the investigated group of elderly patients following an intravenous initial loading dose of 3.7 mg theophylline per kg followed by a continuous infusion of 0.35 mg per kg body weight per hour. In the therapeutic use of theophylline monitoring of the serum theophylline concentration is generally advised because of the elsewhere reported variability in the biological half-life of the compound.


Ability of 6 grams of nitrogen from a combination of rice, wheat, and milk to meet protein requirements of young men for 4 weeks.

Young men consumed a diet that provided 6.0 g of nitrogen, of which rice, wheat, and milk supplied 33, 38, and 29%, respectively, for 28 days following adjustment. This diet contained amounts of essential amino acids that were at least twice the minimal required amounts reported for men. Mean nitrogen balances in four successive 7-day periods were 0.27 +/- 0.13, 0.25 +/- 0.08, 0.10 +/- 0.07 and 0.24 +/- 0.12 g; and the mean for 28 days was 0.22 +/- 0.05 g. Nitrogen retention did not differ significantly between periods. All men who weighed between 65 and 72 kg retained small amounts of nitrogen but one who weighed 78 kg was in slightly negative balance. The mean balances as reported do not provide an allowance for integumental and other losses. The daily protein intake from these sources, equivalent to 0.5 g/kg of body weight, was a critical level slightly lower than the amount appropriate for long-term maintenance of young men weighing 70 kg.


Surgery for lid retraction.

Various methods of surgical correction of lid retraction are discussed. Retraction secondary to overcorrected ptosis surgery is more amenable to correction by various stretching techniques, incising of the levator or recession of the lid elevators. Endocrine lid retraction poses a more difficult problem. Because of the many facets to the problem, a multidisciplined team approach is advised with surgery planned in a stepwise fashion to suit the many interrelated ocular problems of each individual patient.


HLA antigens in autoimmune thyroid diseases.

HLA antigens were determined in 85 unrelated Japanese patients with Graves' disease and 56 patients with Hashimoto's thyroiditis, with the use of the microcytotoxicity test. HLA-Bw35 was found in 36.4% of 85 patients with Graves' disease compared with 13.3% of 150 normal control subjects. This difference in antigen frequency is significant at the level of P less than .0005. The association with HLA-Bw35 in Japanese patients with Graves' diseases is different from that with HLA-B8 in white patients. In patients with Hashimoto's thyroiditis, HLA-Bw35 was also increased (28.5% of 56 patients) but not at a level of statistical significance (P less than .05).


[Lightmicroscopical and histochemical studies on the chorionic plate of the mature human placenta (author's transl)].

The chorionic plate of the normal mature human placenta was studied by light-microscopy and enzyme-histochemistry. Thereby the following findings were obtained in the various layers: The enzyme content of the amniotic epithelium refers to a secretory activity. The question with regard to a resorbant activity remains unclarified. The cells of the amnion mesoderm chiefly show the enzymes of the intermediary metabolism. The intermediate layer consists of mesothelium cells which furthermore have also phagocytotic activity. The chorionic plate mesoderm consists of several layers with connective tissue cells of diverse stage of differentiation. In the early embryonic phase they differentiate amnionward from the primary cytotrophoblast layer and still get cellular supply from residual primary cytotrophoblastic cells up to the date of birth. The enzymes of the primary cytotrophoblast cells refer accordingly with a strong activity of G6PDH to proliferation and differentiation. One part of the X-cells embedded in the Langhans fibrinoid stria descends from this primary cytotrophoblast layer; but in part they differentiate also from the Langhans cells of the placental villi surrounded by the fibrinoid stria. According to their different descent, these cells show a varying content of enzymes. The bordering of the chorionic plate to the intervillous space is represented by a rudimentary, syncytotrophoblast layer.


[Short-term tocolysis of prostaglandin induced uterine contractions comparison between fenoterol and diazoxide (author's transl)].

Uterine contractions were stimulated with a mean dose of 1500 microgram PG in seven pregnant patients between the 14th and 22nd week of pregnancy. The same patients received 300 mg Diazoxide and 20 or 30 microgram Fenoterol alternately in order to tocolize these uterine contractions. After injection of 20 microgram Fenoterol the mean contraction interval lasted for 3.4 min, whereas after 300 mg Diazoxide a mean interval of 48 min was achieved. Side effects after Fenoterol were more marked.


Pathologic changes of endocrine cells in chronic atrophic gastritis. An ultrastructural study on peroral gastric biopsy specimens.

In the course of an ultrastructural study on peroral gastric biopsy specimens that were obtained from patients with chronic atrophic gastritis, peculiar pathological changes of endocrine cells were observed and correlated with functional and hormonal data on the patients. An increased number of G (gastrin) cells was found in hypergastrinemic patients. These cells could be divided into a "light" (probably hyperfunctioning) and a "dark" (probably exhausted) type. The light type of cell was prominent regardless of the concomitant gastrin blood levels. The G cells found within the fundic region were always localized within the areas of pyloric metaplasia. Focal micronodular proliferation of antral enterochromaffin cells (EC) was often seen. A proliferation of the closed type of endocrine cells of the fundic mucosa was observed only in patients with elevated gastrin concentrations. In the present study, these cells were identified as enterochromaffin-like cells (ECL). No substantial changes were found in the D and D1 cells. The endocrine cells seen in metaplastic intestinal epithelium exhibited ultrastruct characteristics of at least three different types of intestinal endocrine cells (EC, L, and S cells).


Malakoplakia of the stomach. Report of a case and review of the literature.

A case of malakoplakia of the stomach associated with well-differentiated adenocarcinoma of the transverse colon was studied by light and electron microscopy. The gross appearance consisted of a slightly elevated plaque with umbilication of the covering mucosa. Histologically, the lesion was composed of submucosal proliferation of histiocytes with the typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. Ultrastructurally, these inclusions had a dense central calcified body and concentric alternating rings. Twenty-four cases of gastrointestinal malakoplakia from the literature, including two cases of gastric malakoplakia, were reviewed.


The glycosaminoglycans of the human colon in inflammatory and neoplastic conditions.

The glycosaminoglycans from normal colonic mucosa and colons with a variety of inflammatory diseases, as well as benign and malignant neoplasms were analyzed. Normal colonic mucosa contains predominantly chondroitin sulfates and dermatan sulfate. Increases in the levels of hyaluronic acid and heparan sulfate, as well as substantial increases in the amount of total glycosaminoglycans were characteristic of invasive colonic adenocarcinoma. Lesser elevations in the amount of total glycosaminoglycans and hyaluronic acid and heparan sulfate were present in neonatal colonic mucosa, villous adenoma, ulcerative colitis, and mucosa adjacent to carcinoma. The degree of elevation was proportional to the dysplastic potential. Since dysplastic lesions have scant connective tissue, the epithelial component of colonic neoplasms may contribute to these neoplasm-related alterations in glycosaminoglycan composition.


Alterations of rat liver subsequent to heat overload.

Since pathological changes in the liver are among the consistent findings in humans subsequent to heatstroke, specimens were taken from the liver in rats during a study to assess the rat as a model for human heatstroke. Tissues from four groups of rats were processed for light and electron microscopy. The groups consisted of control rats, rats run to exhaustion at 5 C, rats exhausted at 26 C, and rats restrained at 41.5 C until their rectal temperatures reached 42.3 C. Exhaustive exercise at 5 C produced neither fatalities nor pathological changes in the livers. Exhaustive exercise at 26 C and restraint at 41.5 C were fatal for most rats. Histological and/or ultrastructural changes, which included centrilobular necrosis, vacuolization and diminution of hepatocellular microvilli, and loss of sinusoidal endothelium, were observed in livers from rats that were run to exhaustion at 26 C and from those rats restrained at 41.5 C. This work supports the validity of the rat model, since human heatstroke results in similar hepatic changes.


Epidural injection of local anesthetic and steroids for relief of pain secondary to herpes zoster.

We treated 12 cases of cutaneous herpes zoster (HZ) with epidural bupivacaine and methylprednisolone acetate. Treatment was effective for HZ of less than seven weeks' duration. The course of HZ of greater than three months' duration (postherpetic neuralgia) was not improved. The administration of epidural bupivacaine plus methylprednisolone acetate was no more effective than when bupivacaine alone was used. Epidural injection of bupivacaine with or without methylprednisolone acetate is the treatment of choice for the pain of cutaneous HZ.


Mutagenicity studies with praziquantel, a new anthelmintic drug, in mammalian systems.

Praziquantel, a new anthelmintic drug with antischistosomal and anticestodal properties, was tested in comparison with a placebo control and a 'positive control' with cyclophosphamide in mammalian test system in vivo for potential mutagenic effects. The test systems used and the tested doses of Praziquantel were: (1) Dominant lethal test on male NMRI mice, 12 mating periods of 4 days each, 1 X 1200 mg/kg BW by mouth; (2) Dominant lethal test on female NMRI mice, treatment during pre-estrus, 1 X 1200 mg/kg BW by mouth; (3) Micronucleus test on male and female NMRI mice, two doses with a 24-h interval and preparation of the femoral marrow 6 h after the second dose, 2 X 300 mg/kg and 2 X 600 mg/kg BW by mouth; (4) Spermatogonial test on the Chinese hamster, two doses with a 24-h interval and preparation of the spermatogonia 48 h after the second dose, 2 X 600 mg/kg BW by mouth. The 1200 mg/kg BW dose corresponded to approximately 1/2 of the LD50 after oral application in the mouse and about 40 times the therapeutic dose (1 X 30 mg/kg BW). The cyclophosphamide doses in the test systems were 1 X 200 mg/kg or 2 X 200 mg/kg BW by mouth. No indication was found of any mutagenic potency of Praziquantel. This agrees with the results of point-mutation tests done by other authors.


[Medicolegal aspects of poisoning (author's transl)].

8679 post mortem dissections have been performed in the Institute during the rescent 25 years; 563 of them have been cases of poisoning (=6.5% of totality). They were grouped for the years 1950--1965 and 1966--1975. Suicidal poisoning showed an increasing, poisoning in children a decreasing tendency during the last 25 years. Suicides were mainly performed with hypnotics. Carbon monoxide poisoning dominated in the group of accidental poisoning.


Isolation of drugs from blood by column chromatography on Amberlite XAD-2.

An investigation was carried out on the isolation of 28 drugs from blood by column chromatography on Amberlite XAD-2. The following substances were added to postmortem blood specimens at concentrations generally of 1--10 microgram/ml: barbital, heptabarbital, hexobarbital, pentobarbital, phenobarbital, phenylbutazone, monocrotophos, amidopyrine, carbromal, diazepam, meprobamate, methaqualone, nitrazepam, phenazetin, chlorpromazine, dibenzepin, diphenhydramine, haloperidol, imipramine, mescaline, methadone, morphine, pentazocine, pethidine, tilidine, triflupromazine, verapamil, N-propylajmalinium bitartrate. The samples were purified by column chromatography on Amberlite XAD-2 and simple solvent extraction and subsequently quantitated by gas chromatography. By systematic variation of the conditions for adsorption of the drugs and desorption from the resin, revoveries of more than 80% after XAD-2 column chromatography could be achieved for most drugs. Thereby it was demonstrated, that in cases of fatal poisoning or emergencies this procedure is a valuable tool for forensic and clinical toxicologists who have to find out the toxic agent by chemical analysis of the blood.


The influence of unithiol and spironolactone on the biliary excretion of 203Hg in rat.

Rats with cannulated bile ducts were intravenously given 203HgCl2 in the dose of 120 microgram of Hg2+ per rat. Intramuscular administration of Unithiol (sodium 2,3-dimercaptopropanosulphonate) 4 and 7 h after 203Hg injection markedly increased both biliary and urinary excretion of 203Hg. In rats with Spironolactone (17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid, gamma-lactone, acetate) pretreatment the effect of Unithiol on the biliary excretion of 203Hg was enhanced. Urinary excretion of mercury was lowest in comparison with Unithiol treated group.


A rapid gas-chromatographic method for the determination of drugs in clinical toxicology.

A rapid gas-chromatographic method for the qualitative and quantitative measurement of various drugs in human plasma and other body fluids has been developed. The extraction procedure is done within 5 min, and gas-chromatographic measurement carried out on 2 diverse columns with detection by flame ionisation detectors. The detection sensitivity of most drugs is high enough to determine their plasma levels in suicidally or accidentally poisoned patients. As shown for 6 different drugs, the limit of detection, the reproducibility and the accuracy are sufficient even for analysis of therapeutical plasma concentrations.


Distribution and excretion of the mercury chelating agent sodium 2,3-dimercaptopropane-1-sulfonate in the rat.

The distribution and excretion of sodium 2,3-dimercapto-1,3 14C-propane-1-sulfonate as dependent on time has been studied in the rat. The highest concentration is found in the kidneys, the lowest in the brain. The excretion is very rapid (T1/2 = 19 min) and follows a monoexponential curve during the first hour after administration. This holds for plasma and most of the organs too. The apparent distribution volume of the radioactivity is equivalent to the volume of the extracellular water. After oral administration, 30-40% is absorbed from the gut. The results lead to the conclusion that a fraction of the drug is weakly bound to plasma- and membrane-proteins. They are discussed with respect to the treatment of heavy metal poisoning.


[Critical comments on a case history "a death case involving tilidine" (author's transl)].

The author looks critically at the description of a suicide case involving a barbiturate dose that could not be determined exactly and doses of hydroxyzine and tilidine. Drugs with a short and a medium short duration of action obviously had the greatest effect. There was no description of an investigation of the gastric contents. The concentration of barbiturates in the blood alone was sufficient to cause death. The deceased also took hydroxyzine, and then finally 750 mg tilidine in capsule form. Tilidine's action is relatively slow in onset. The author discusses tilidine's possible contribution to the cause of death and comes to a different conclusion from the authors of the case report, especially as regards the key words "Tilidine--Intoxication". The authors of the case report ought to have called it "A Death Case Involving Barbiturates, Hydroxyzine and Tilidine" rather than giving is such a suggestive title as "A Death Case Involving Tildine". This would have been a more accurate representation of the facts and would have assisted the reader to grasp the complex toxicological situation more clearly.


Methemoglobin formation and binding to blood constituents as indicators for the formation, availability and reactivity of activated metabolites derived from trans-4-aminostilbene and related aromatic amines.

trans-4-Aminostilbene derivatives exhibit higher acute and chronic toxicity than 4-aminobibenzyl derivatives. Yet, trans-4-aminostilbene produced less methemoglobin in female Wistar rats than 4-aminobibenzyl. This cannot be explained by differences in N-oxidation since trans-4-nitrosostilbene was also less efficient than 4-nitrosobibenzyl. The fate of intravenously injected, highly and specifically 3H-labeled trans-4-aminostilbene, cis-4-aminostilbene, 4-aminobibenzyl, trans-4-nitrosostilbene and 4-nitrosobibenzyl was investigated. The results indicate that trans-4-aminostilbene and 4-aminobibenzyl are N-oxidized to a similar extent and primary activation products of trans-4-aminostilbene appear even faster in the blood. However, intermediates originating during methemoglobin formation are more reactive and covalently bind to hemoglobin 2--3 times as much with trans-stilbene as compared to bibenzyl derivatives. As a consequence the availability of these intermediates in the cyclic process and thus methemoglobin formation is reduced. Therefore, binding to hemoglobin rather than levels of methemoglobin appears to be an indicator for the availability and reactivity of some activated aromatic amine metabolites.


Metabolism of pentachlorophenol in vivo and in vitro.

Pentachlorophenol has earlier been shown to be metabolized in mammals to tetrachloro-p-hydroquinone. The metabolite possesses pronounced inhibitory activity on bacterial beta-glucuronidase but not on beta-glucuronidase from liver. Indirect evidence for the occurrence of both pentachlorophenol and tetrachloro-p-hydroquinone as conjugates with glucuronic acid in the urine from pentachlorophenol-treated rats is now presented. Bovine liver beta-glucuronidase has been utlizied to split the conjugates present. The in vivo metabolism of pentachlorophenol has also been studied in rats treated with phenobarbital and beta-diethylaminoethylidiphenyl propylacetate (SKF 525-A). In vitro metabolism has been studied using liver microsomes from rats pretreated with pehnobarbital. Quantitative analysis of the compounds occurring in extracts of urine or extracts from the microsomal incubates was performed by means of mass fragmentography. Pretreatment with phenobarbital increased the metabolism of pentachlorophenol to tetrachloro-p-hydroquinone both in vivo and in vitro. SKF 525-A, however, inhibited the metabolism in vitro but enhanced the metabolism in vivo when given less frequently than every 6th h. Dechlorination of pentachlorophenol is mediated by microsomal enzymes that can be induced by phenobarbital. SKF 525-A does not inhibit the dechlorination in vivo but does so in vitro.


Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the in vivo and in vitro dechlorination of pentachlorophenol.

The metabolism of pentachlorophenol has been studied in the rat after pretreatments with phenobarbital, 3-methyl cholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to the previously identified metabolite, tetrachloro-p-hydroquinone, trichloro-p-hydroquinone has been identified in urine as a metabolite. The formation of the latter represents a type dechlorination different from that of the formation of tetrachlorohydroquinone. The inducing agents, 3-methylcholanthrene and TCDD have similar effects on the dechlorination and increase the formation of tetrachloro-p-hydroquinone more pronounced than does phenobarbital. In contrast to phenobarbital they also increase the formation of trichloro-p-hydroquinone and the total elimination of pentachlorophenol and its metabolites. The in vivo findings are supported by in vitro studies with microsomes from rats pretreated with phenobarbital or TCDD. Use of the inhibitor beta-diethylaminoethyl-diphenyl propylacetate (SKF 525-A) in vitro showed a more pronounced inhibition on microsomes from phenobarbital-treated rats than on microsomes from untreated or TCDD-treated rats. Gas chromatography-mass spectrometry have been used for the identification and quantification of pentachlorophenol and its metabolites.


Metabolism of tetrachlorophenols in the rat.

The three isomers of tetrachlorophenol were administrated intraperitoneally to rats and the urinary excretion products studied. Tetrachloro-p-hydroquinone was identified as a major metabolite of 2,3,5,6-tetrachlorophenol, constituting about 35% of the dose given. Trichloro-p-hydroquinone was identified as a minor metabolite of both 2,3,4,5- and 2,3,4,6-tetrachlorophenol. 2,3,5,6-tetrachlorophenol was eliminated within 24 h, 2,3,4,6-tetrachlorophenol within 48 h while only 60% of the given dose of 2,3,4,5-tetrachlorophenol could be recovered within 72 h. The acute toxicity of the tetrachlorophenols and tetrachloro-p-hydroquinone was studied in mice upon oral and intraperitoneal administration. 2,3,5,6-tetrachlorophenol (LD50p.o. 109 mg . kg-1) was the most toxic compound followed by 2,3,4,6- and 2,3.4,5-tetrachlorophenol (LD50p.o. 131 and 400 mg . kg-1, respectively). Tetrachloro-p-hydroquinone proved to have low oral toxicity (LD50p.o. 500 mg . kg-1) but was more toxic than the tetrachlorophenols when administered intraperitoneally. The oral LD50 for pentachlorophenol, under identical experimental conditions was found to be 74 mg . kg-1.


Rapid temperature-induced changes in the fatty acid composition of certain lipids in developing linseed and soya-bean cotyledons.

A change in ambient temperature caused marked alterations, over a 24h period, in the proportions of the unsaturated C18 fatty acids in 3-sn-phosphatidylcholine and 1,2-diacyglycerols during the development of soya-bean and linseed cotyledons. The molar proportion of oleate increased when the temperature was increased whereas that of linoleate or linolenate, depending on the species, increased when the temperature was lowered. Concomitant changes in the composition of 3-sn-phosphatidylethanolamine and triacylglycerols were small.


Labelling of glycerolipids in the cotyledons of developing oilseeds by [1-14C] acetate and [2-3H] glycerol.

1. 3-sn-Phosphatidylcholine was identified as the major lipid in cotyledons from the developing seeds of soya bean, linseed and safflower when tissue was steamed before lipid extraction. The proportion of oleate in this lipid decreased markedly and that of the polyunsaturated C(18) fatty acids increased when detached developing cotyledons were incubated for up to 3h. Similar but less pronounced changes occurred in diacylglycerol, which had a fatty acid composition resembling that of the 3-sn-phosphatidylcholine from cotyledons of the same species. 2. [1-(14)C]Acetate supplied to detached cotyledons was incorporated into the acyl moieties of mainly 3-sn-phosphatidylcholine, 1,2-diacylglycerol and triacylglycerol. Initially label was predominantly in oleate, but subsequently entered at accelerating rates the linoleoyl moieties of the above lipids in soya-bean and safflower cotyledons and the linoleoyl and linolenyl moieties of these lipids in linseed cotyledons. In pulse-chase experiments label was rapidly lost from the oleate of 3-sn-phosphatidylcholine and accumulated in the linoleoyl and linolenoyl moieties of this phospholipid and of the di- and tri-acylglycerols. 3. [2-(3)H]Glycerol was incorporated into the glycerol moieties of mainly 3-sn-phosphatidylcholine and di- and tri-acylglycerols of developing linseed and soya-bean cotyledons. The label entered the phospholipid and diacylglycerol at rates essentially linear with time from the moment the substrate was supplied, and entered the triacylglycerol at an accelerating rate. With linseed cotyledons the labelled glycerol was incorporated initially mainly into species of 3-sn-phosphatidylcholine and diacylglycerol that contained oleate, but accumulated with time in more highly unsaturated species. In pulse-chase experiments with linseed cotyledons, label was lost from both 3-sn-phosphatidylcholine and diacylglycerol, preferentially from the dioleoyl species, and accumulated in triacylglycerol, mainly in species containing two molecules of linolenate. 4. The results suggest a rapid turnover of 3-sn-phosphatidylcholine during triacylglycerol accumulation in developing oilseeds, and are consistent with the operation of a biosynthetic route whereby oleate initially esterified to the phospholipid is first desaturated, then polyunsaturated fatty acids transferred to triacylglycerol, via diacylglycerol. The possible role of oleoyl phosphatidylcholine as a substrate for oleate desaturation is discussed.


[Isolation and structural definition of a new sennoside from Cassia senna L. (author's transl)].

The optical isomer of sennoside A--called sennoside A1--postulated by Stoll already in 1950--was isolated from senna pods. Structure identification was carried out by TLC, HPLC, UV, CD and MS.


[Determination of antimicrobial activity of a combination of acidamfenicol, clotrimazole and dexamethasone in vitro (author's transl)].

The in vitro antimicrobial activity of the antieczematic Bay f 4797 was studied. This combination drug contains the three active components acidamfenicol, clotrimazole and dexamethasone (prospective trade name: Baycuten). Various bacterial and fungal species of importance in dermatology served as test organisms. All the bacterial strains examined were found to be moderately susceptible to acidamfenicol; clotrimazole showed good inhibitory values agaisnt all the fungal species and the gram-positive bacterial strains. Additionally it was checked whether a synergistic or antagonistic interaction occurs with respect to the antimicrobial activity. An interference which could lead to impairment of the therapeutic activity was not observed.


[Antimycotic drugs. 5th Communication: carbocyclically and heterocyclically substituted trifluoromethylpyrimidines (author's transl)].

In view of the role that methoxy and methylthio groups play in antimycotic drugs, 2-methoxy- and 2-methylthio-trifluoromethylpyrimidines (3a-h) have been developed by condensation of O-methylisourea (1a) or S-methylisothiourea (1b), respectively, with beta-diketones (2a-d). Opposed to this course, the reaction of 1b with 1,1,1,2,2,3,3-heptafluoro-6-(2-thienyl)-4,6-hexanedione (4) fails to lead to ring closure but rather yields 4,4,5,5,6,6,6-heptafluoro-3-(2-methyl-1-thioureido)-1-(2-thienyl)-1-hexen-1,3-diol (5).


[The influence of some carbamazepin metabolites on Nielsen's quantitative determination. 5th communication: on chemistry and analytics of dibenzazepine derivatives (author's transl)].

H. R. Nielsen and H. Remmer described a quantitative method for the estimation of carbamazepin serum levels. The specificity of this method was examined with the result that besides carbamazepin also its metabolites react under the authors' conditions.


Indirect atomic absorption analysis of ethambutol.

In the presence of cupric ions and sodium hydroxide, ethambutol forms a chelate compound which can be extracted with ethyl-methyl ketone. The amount of ethambutol-copper complex was determined by measuring the copper by Atomic Absorption Spectroscopy (AAS) in the ethylmethyl ketone extract. When this method was applied to pharmaceutical samples satisfactory results were obtained. The method is accurate for routine analyses and very simple to be carried out.


N-Acetylcysteine and mucociliary activity in mammalian airways.

The effect of N-acetylcysteine on mucus trasnport velocity (MV), ciliary beat frequency (CBF), mucus production (MP), mucus lysis and on the micro-morphology of the secretory cells was studied in mammalian airways. The results showed that: 1. MV increased in healthy rats and rabbits, as well as in bronchitic rats, after concentrations as low as 10(-14) g/ml. Depression of MV occurred first at 10(-6) and 10(-5) g/ml  in healthy and bronchitic animals, respectively. 2. CBF was stimulated at concentrations between 10(-12) and 10(-10) g/ml and decreased at concentrations above 10(-8) g/ml. 3. MP increased by approximately 100% over control values. 4. Lysis of stagnant mucus was evident first at a concentration of 10(-11) g/ml after 15 min incubation. 5. TEM confirmed the increased activity of the mucus secreting cells and showed that no pathological changes occurred within the cell following incubation at 10(-7) g/ml for up to 150 min. The importance of these findings on the overall mucociliary function is discussed.