[The effect of memantine (dimethylamino-adamantane) on membranes of sensory nerve fibres (author's transl)]. The effect of memantine (dimethylaminoadamantane), a new amantadinederivate with antiparknison-properties was investigated by the help of the sucrose gap method on sensory nerve fibres of the rat In normal Locke-solution memantine 10(-4) M reduced the amplitude of the compound action potential without change of the resting potential, increased the membrane resistance and depressed the repetitive activity elicited by depolarizing rectangular currents. The results of the experiments with changed concentrations of sodium, potassium and chloride ions in the suspensionmedium indicate that the membrane conductance of all three ions was reduced by memantine. Beside the antiparkinson properties these effects as well as those reported by others might be interpreted as a central muscle relaxing action of memantine. The possible implication of the demonstrated membrane effects of the drug is discussed in relation to its action on the dopaminergic transmission in the nigro-striatal system.


The influence of acetysalicylic acid on changes in platelet function due to physical exertion. The influence of acetylsalicylic acid (ASA) on alterations of the platelets resulting from physical exertion was studied in 10 healthy volunteers. Before and 2 h after the administration of placebo or 1 g ASA, venous blood samples were taken for platelet counts, thrombelastography (TEG) and tests of ADP- and epinephrine-induced platelet aggregation. The blood in which the 2-h values were determined was sampled at the highest work-load during sub-maximum exercise on a bicycle ergometer (5 min each at 50, 100 and 150 watts). ASA had no effect on the alterations of the platelets due to physical effort: the increase in the first phase of epinephrine-induced aggregation, the elevation of the platelet count and the hypercoagulability demonstrable by TEG still persisted after the administration of ASA. Some effects were noted, however, that are also observed after the administration of ASA at rest: the second phase of epinephrine-induced aggregation was suppressed and disaggregation after induction with ADP was accelerated.


[The influence of the combination of coumarin and troxerutin on infantile blood parameter in lactation period. Short communication (author's transl)]. The examination of the hematological parameters erythrocytes, hemoglobin, thrombocytes, thrombelastogram, prothrombin time, blood-clotting and bleeding time in 20 mothers and their infants proved that the combination of coumarin and troxerutin (Venalot) can be administered in elevated doses unhesitatingly. All values tested were within normal ranges before and after treatment.


Local treatment of thoracic empyema with tri-tetracycline complexes. In 13 patients with thoracic empyema of different origins, aqueous solutions of tri-metacycline or tridoxycycline were administered locally into the pleural cavity by puncture or through a drain-tube. Depending on the sensitivity of the causative agent, the former antibiotic was used in 12 cases and the latter in 1 only. The urinary output of the antibiotic was followed by chromatography. The local treatment cleared up the previously purulent exudate in 11 patients, while in the remaining two cases the efficacy of the therapy could not be evaluated.


Influence of canrenoate-K and cardiac glycosides on their tissue distribution and elimination. The combination of cardiac glycosides and canrenoate-potassium (CR-K) produces synergistic effects on hemodynamics. On the other hand, CR-K antagonizes digitalis-induced cardiac arrhythmias. Therefore, it was the purpose of this study to determine interactions between these substances, particularly of their myocardial uptake. The additional administration of CR-K leads to significantly higher concentrations of digoxin and ouabain in heart, liver, adrenal gland and spleen. Contrary to this, additional digoxin reduces the concentration of CR-K in the tissue. Particularly obvious is the reduced concentration in the kidney, adrenal gland, pancreas, brain and spleen. The renal excretion of digoxin and ouabain is reduced by the additional administration of CR-K, while digoxin accelerates the CR-K excretion within the first 60 min after application. Metabolic interference was not detected in the combination of cardiac glycosides and CR-K. The mechanisms for the interactions between cardiac glycosides and CR-K during the distribution phase are discussed. The inhomogenous interference of their myocardial uptake makes a common cardiac receptor for the synergistic effect of cardiac glycosides and CR-K rather unlikely. CR-K does not have a suppressant effect on digitalis-induced arrhythmias due to any diminution of the glycoside uptake by myocardial tissue.


Acute nonlymphocytic leukemia in patients with nodular lymphoma. Acute nonlymphocytic leukemia (ANLL) developed in four patients 66 to 157 months following the diagnosis of nodular poorly differentiated lymphocytic lymphoma (PDL-N). The ANLL was signalled by increasing anemia and thrombocytopenia. A characteristic cytologic pattern of the leukemia was found. In each patient, a panmyelosis was present with striking morphologic abnormalities in leukocytes, erythrocytes and megakaryocytes. Marrow cytogenetic studies demonstrated abnormalities in all three patients studied. One of three patients treated with intensive chemotherapy obtained a complete remission. When long term survivors with PDL-N develop increasing anemia and thrombocytopenia, morphologic and cytogenetic marrow examinations are indicated to distinguish progressive lymphoma from therapy-induced myelosuppression or ANLL.


Thymoma and primary lymphoma of the small intestine. A case or primary poorly differentiated lymphocytic lymphoma of the ileum in a patient previously found to have an epithelial thymoma is described. While the frequency of malignancies of many types is increased in patients with thymoma, malignant lymphomas represent the most commonly associated tumor type. Lymphomas in these patients may devleop as a result of defective immunologic surveillance, impaired immunoregulation in partially immuno-deficient hosts, or by immunostimulation. The intestinal origin of the tumor in this case suggests that it may have developed as a result of local stimulation of lymphoid tissues by an antigen or antigens present in the intestinal contents.


Absorption and excretion of carbenicillin indanyl sodium in patients with reduced kidney function. On eight volunteers with reduced kidney function, 1 g of carbenicillin indanyl sodium was administered orally for the single dose studies and was given orally in a dose of 1 g every 6 h for 7 days for the multiple dose studies. The patients were divided into two groups according to their kidney functions: group I moderately impaired and group II severely impaired. In the single dose studies, the mean peak level was 12.6 microgram/ml for group I and 26.9 microgram/ml for group II. In the multiple dose studies, the drug tended to accumulate in group II, but the level obtained in group II did not exceed more than 300 microgram/ml. In the single dose studies, the mean peak level in the urine was 1,478.5 microgram/ml for group I and 350.0 microgram/ml for group II. In the multiple dose studies, despite the multiple dose regimen, the level obtained from group II patients only transiently exceeded more than that which will effectively inhibit the growth of Pseudomonas, Klebsiella and Enterobacter. In the single dose studies, the mean cumulative amount excreted in the urine within 24 h was 314.2 mg for group I and 120.1 mg for group II and the difference between both groups was significant (p less than 0.05). For the multiple dose studies, the amount was 278.0 mg for group I and 127.2 mg for group II, respectively. The total amount excreted in the urine within 24 h and the serum level obtained 6 h after ingestion of 1 g of carbenicillin indanyl sodium was correlated to the creatinine clearance and the rate of PSP excreted in the urine within the first 15 min of the test.


[Retrolental fibroplasia: retrospective study (author's transl)]. Retrolental fibroplasia (RLF) is an iatrogenic disease of immature or dystrophic newborns who had been given oxygen treatment. Exchange transfusions seem to be of aetiological importance because they change the oxygen dissociation curve. Oxygen treatment of the newborn requires exact monitoring which can be done only in specially equipped departments. The retinal changes, up to the full-blown picture of RLF, progress rapidly. Ophthalmological control is, therefore, necessary as early as four weeks of age. If early RLF changes are demonstrated serial examinations every two weeks are indicated so that, if progression is demonstrated, treatment can be instituted.


Lactobezoar in an infant: an unusual cause of upper abdominal tumour persisting for several weeks. Case report and review of the literature. A case of lactobezoar is described in an eleven weeks old infant with a history of prolonged vomiting and constipation. The feeding history revealed no abnormalities, but unusually high environmental temperatures plus increased sweating may have been responsible for the formation of the gastric milk coagulum which presented as a firm epigastric tumour persisting for several weeks. An abdominal neuroblastoma was suspected but the correct diagnosis was established by a barium meal. Conservative therapy with parenteral fluids and gentle gastric lavage resulted in prompt disintegration of the lactobezoar. The 9 previously reported cases in the literature are briefly discussed.


Metabolism and physiologic roles of vitamin E. Antioxidant effect of vitamin E averts hemolytic anemia in low-birthweight infants fed formula rich in polyunsaturated fatty acids and iron. Tocopherol supplementation has also been shown to decrease the incidence and severity of retrolental fibroplasia and the development of bronchopulmonary dysplasia. Although the vitamin lowers platelet hyperaggregability, its role as an antithrombotic agent is still unclear.


[Neurotropic action of probon compared to amidopyrine]. In comparing the neurotropic action of probon and amidopyrine it became evident that both analgesics inhibit the behavioral reactions of rats in "open field" tests, fail to produce any protective action with respect to the reflex reaction of the heart in response to pain stimulation and attenuate such an effect of seduxen. By lengthening the hexobarbital-induced sleep probon and amidopyrine change the EEG nature typical of the effect produced by barbiturates. The difference between the study analgesics is rather a quantitative one, viz. in many rests probon is more potent and its action manifestes itself in a wider range of dosages.


[Membrane stabilizing effect of medicinal substances used for the treatment of chronic venous insufficiency]. Experiments "in vitro" have brought evidence that butadion, escinol, esculetin, glyvenol, rutin, escin and the summary flavor noid preparation are capable of stabilizing erythrocytes membranes with the cells subjected to hypotonic hemolysis. Depending upon optimal concentrations the activity of the substances was within the range of 10(-3) to 10(-8). As concerns the intensity of the effect in the optimal concentration (10(-5) M), that corresponds to the one built up in the blood of patients given the therapeutic dose of the drug, the action of glyvenol was 1.6-3.5 times superior to that of the other compounds.


Lung surface tension and air space dimensions from multiple pressure-volume curves. Pressure-volume (PV) curves of excised cat, dog, rabbit, and rat lungs were determined in a sequence of three conditions: 1) normal-surface, air-filled; 2) saline-filled; and 3) polyoxyethylene (20) sorbitan monolaurate-(Tween 20) surface, air-filled. Since the surface tension of lung washings containing 2% Tween 20 is constant, the Tween-surface air-filled lungs presumably exhibit the pressure-volume behavior of lungs with constant surface tension. These data along with the assumption of equivalent geometry in the three conditions permit calculation of the variation of surface tension in the normal lung as a function of volume without assuming a specific surface area vs. volume function or a maximum surface tension. The calculated surface tension dropped during deflation from a high of 50 dyn/cm total lung capacity (TLC) to a low of 4 dyn/cm (less than 25% TLC) with the species being roughly similar. The PV behavior of Tween-surface lungs appears to fit a simple model of alveolar expansion. Air dimensions calculated for the four species on the basis of this model are ordered in the same sequence as morphological measurements, but larger in magnitude.


Competency-based training for severely behaviorally handicapped children and their parents. This paper describes the major components of a treatment program for severely behaviorally handicapped children. The program's goal is to help the children develop the necessary skills to function in regular classrooms or special education classes. The article presents descriptions of the procedures used in the Day School Learning and Treatment Center and the Parent Training Program at the Judevine Center for Autistic Children. Criteria for acceptance, assessment systems, training techniques, and methods for follow-up are outlined. Also, the paper delineates what are considered to have been five major trends in the development of the program.


Cognitive characteristics of parents of autistic children. The parents of 15 autistic boys with a nonverbal IQ of at least 80 were compared with a matched group of parents of normal boys on the Goldstein-Scheerer Object Sorting Test and the Bannister-Fransella Grid Test of Thought Disorder. It was necessary to control for social class effects as abnormal scores on the thought disorder tests were more frequent in parents of manual social class. It was found that (a) there was a lack of agreement between the two tests of thought disorder, (b) the parents of autistic children showed thought disorder scores closely comparable to those of the parents of normals, and (c) there was no consistent association between thought disorder and anxiety. The methodological and substantive implications of the findings are discussed in relation to the results of previous investigations.


A case report of an autistic girl with an extra bisatellited marker chromosome. Cytogenetic examination of a 14-year-old severely retarded girl revealed a karyotype of 47 chromosomes with an extra bisatellited chromosome, a translocation between No. 22 and a chromosome in the D group. The girl had presented an early autistic syndrome beginning about 6 months of age during plastering for a congenital luxation of the hips and receding from the age of 5. In addition, she was hyperkinetic with various aggressive and auto-aggressive traits and had atypical minor epileptic fits. Data from child psychiatric examinations at 5 and 14 years are presented. The importance of giving parents information as early as possible about biological causes of mental retardation and mental illness is stressed.


Detection, pathogenesis, and prevention of damage to human granulocytes caused by interaction with nylon wool fiber. Implications for filtration leukapheresis. Granulocytes collected by reversible adhesion to nylon wool fiber (NWF) function relatively well in standard in vitro tests; however, they have an abnormally shortened survival time in the circulation. Assuming that this rapid disappearance represents clearance and that recognition by phagocytes is important for such clearance, we used an autologous in vitro cell:cell recognition assay to determine whether phagocytes can detect cellular changes induced by exposure of normal granulocytes to NWF. Human granulocytes incubated with NWF 1 h at 37 degrees C, eluted with 20% acid citrate dextrose plasma, and washed stimulated the hexose monophosphate shunt activity of normal granulocytes an average of twofold (193+/-40% of controls), indicating a recognition response. NWF-induced granulocyte recognition was not dependent on plasma factors or activated complement components but was dependent on the time that the granulocyte was on the NWF and was maximal by 60 min of exposure. After elution from NWF, granulocytes demonstrated resting glucose oxidation rates only slightly higher than normal; however, during the first 20 min of exposure to NWF, granulocytes increased their rate of (14)CO(2) production from [1-(14)C]glucose three- to five-fold. Therefore, experiments were performed to determine whether toxic oxygen metabolites produced by NWF-adherent cells might contribute to recognition. The results showed that (a) normal granulocytes exposed to NWF in the presence of scavengers of superoxide anion (superoxide dismutase) or free radicals (ascorbate, mannitol, or benzoate) and washed before assay did not stimulate glucose oxidation of indicator granulocytes; and (b) NWF granulocytes prepared from cells unable to generate high levels of toxic oxygen metabolites, i.e. cells prepared anaerobically or from a patient with chronic granulomatous disease, also failed to stimulate indicator granulocytes. Human granulocytes placed in contact with NWF show an oxidative burst and become recognizable to other phagocytes. Free radical scavengers are effective in minimizing this recognition conferred on NWF-procured granulocytes.


Potential systemic side effects of six common ophthalmic drugs. Drugs applied topically on the eye are partly absorbed into the eye (possibly 2 to 10%), the remainder can enter the systemic circulation through the conjuctival vessels or from the vessles of the nasolacrimal passages. Drug molecules which enter the stomach and are not transformed into inactive compounds may also enter the blood stream. Systemic reactions to topically applied ophthalmic drugs are shown to be rare and largely preventable.


Tetanus antibody production in serum and cerebrospinal fluid in the rabbit and correlated histopathological features of the central nervous system. The histopathological features in the central nervous system (CNS) developing during the active phase of tetanus antibody formation in the cerebrospinal fluid (CSF) as induced in 15 rabbits were studied. The measurement of antibody titres in serum and CSF by electroimmunodiffusion and histological examination were done sequentially at the 1st, 3rd, 5th, 7th and 9th days after cisternal secondary inoculation with fluid tetanus toxoid. Tetanus antibodies appeared in serum after the 1st and in CSF after the 5th day. Decreasing values of CSF total protein were found. The meaning of an elevated Q ratio as observed in this situation of strong  antibody formation in the CSF was enhanced. The histopathological features in the central nervous system consisted of perivascular inflammatory infiltration, at first polymorphic and then composed almost exclusively of mononuclear cells with a predominantly leptomeningeal and subpial localization, which might represent the origin of CSF tetanus antibodies. The localization was related to the contact zone between the antigen- and antibody-containing compartments, respectively the subarachnoid space and vascularized structures of the brain and spinal cord. Four control rabbits presented neither tetanus antibodies in the CSF nor perivascular inflammatory infiltration in the CNS. Similarity between the present experimental results and the immunopathological features of the primary demyelinating diseases provides some useful information about the immunological inflammatory events in these diseases.


Kinetics and mechanisms of monolayer interactions IV: Surface activity of alkanols and energies of their interaction with dipalmitoyllecithin and dipalmitoylphosphatidylethanolamine. The free energies of adsorption of the C1 to C14 alkanols at the air--water interface, estimated from plots of the surface pressure (pi less than or equal to 5 dynes/cm) against the bulk concentration, were a linear function of the chain length for 1-alkanols. From C3 to C8, the 2- and 3-isomers showed lower values than the 1-isomers. The energies of interaction of the C1 to C14 alkanols with dipalmitoylphosphatidylethanolamine and dipalmitoyllecithin monolayers, previously spread at the air-water interface, were estimated from the increase of the surface pressure with increasing concentrations of the injected alkanol. The energies of interaction of the C1 to C5 1-alkanols were linear functions of the chain length. The energy of interaction per methylene group of the alkyl chain suggests that the phospholipid monolayers behaved as ultrathin "oil" phases. The 2- and 3-isomers presented marked departures from linearity. The literature data for reflection coefficients in biomembranes and for partition coefficients between olive oil and water, red cell membranes and water, and phospholipid liposomes and water for the C1 to C5 alkanols show similar linearities with the chain length for the 1-isomers and comparable departures for the 2- and 3-isomers.


Radioimmunoassay for normeperidine: studies on the N-dealkylation of meperidine and anileridine. A sensitive and specific radioimmunoassay for normeperidine has been developed that can detect as little as 100 pg of this metabolite. In competitive binding experiments with [125I]O-tyramyl-normeperidinic acid and an antiserum produced in rabbits immunized with a bovine serum albumin-normeperidinic acid conjugate, meperidine is only 0.01% as effective an inhibitor as normeperidine. Therefore, normeperidine can be determined in physiological fluids and in tissue extracts when relatively large amounts of meperidine or other N-phenylpiperidine esters are present. High pressure liquid chromatography can be used to confirm the results obtained by radioimmunoassay during the in vitro N-dealkylations of meperidine and anileridine to normeperidine. The normeperidine isolated by high pressure liquid chromatography accounts for all of the inhibitory reactivity determined in the enzymatic digests by the radioimmunoassay. Kinetic parameters (Km and Vmax) can be determined for the N-dealkylation of meperidine and anileridine. The formation of normeperidine with time can be followed in rabbits injected with meperidine or anileridine. Plasma levels may also be determined when meperidine is administered as an obsteric analgesic.


Arthropathy as the major clinical indicator of occult iron storage disease. Chronic arthritis was the only symptom that led to the detection of increased iron stores in four patients. In these persons, the serum iron was ordered at the time of initial examination, and ranged from 212 to 237 microgram/dl with a transferrin saturation of 83% to 100%. Liver biopsy specimens showed hepatocyte iron deposition in each person, with definite cirrhosis in only one patient. These cases illustrate that a chronic arthropathy may be the first clinical manifestation of iron overload, and can lead to discovery of the disease in patients and their family members. Treatment may then be initiated before extensive tissue damage has occurred.


Zonal colonic hypoganglionosis.

Zonal colonic hypoganglionosis. We report the case of a patient with chronic constipation since birth, a strictured area in the distal sigmoid colon, and histologic findings of localized hypoganglionosis. We have compared this entity (zonal colonic hypoganglionosis) and reviewed the literature of all known cases of zonal colonic aganglionosis and hypoganglionosis.


Pulmonary perfusion defect and bronchial artery collateral blood flow. A five-year-old child with severe congestive heart failure following repair of tetralogy of Fallot was examined for correction of a suspected left-to-right shunt. Lung scan and selective bronchial angiographs demonstrated greatly diminished perfusion to the right upper lobe, which was supplied by a large bronchial artery. Technetium microspheres were injected into the artery for quantification. Subsequently, the artery was occluded by injection of the tissue-adhesive bucrylate. During the following year, radionuclide scans showed improvement in the uniformity and percentage distribution of pulmonary perfusion by way of the pulmonary artery. The child has become asymptomatic following closure of the bronchial vessel.


A simulated patient-physician encounter using a talking computer. Computer-based clinical simulations provide a means for evaluating the information-gathering and patient-management competencies of physicians. The need for expensive computer terminals has restricted physician use of these simulations. This computer-based program permits physicians to complete computer-based encounters using a standard touch-tone telephone.


Effect of clonidine on atrioventricular conduction. Clonidine hydrochloride may be a factor in producing a high-grade atrioventricular block. Therefore, careful follow-up with repeated ECG monitoring seems to be indicated when clonidine is given to a patient with suspected cardiac conduction disease, especially if the patient is concurrently receiving digitalis therapy.


Doxycycline in abdominal surgery.

Doxycycline in abdominal surgery. Twenty patients undergoing urgent or emergency surgical procedures where intra-abdominal infection was suspected were treated with doxycycline hyclate. Wound infections involving anaerobic, aerobic, or facultative bacteria developed in four of 11 patients treated with doxycycline alone. Nine other patients received higher doses of doxycycline plus gentamicin sulfate. Five of these had postoperative infections primarily involving anaerobic organisms. Bacteremia with a doxycycline-resistant Bacteroides fragilis developed in one patient during therapy. Serum levels of doxycycline, even at the higher dosage, were below the minimal inhibitory concentrations (MICs) of a number of potential pathogens isolated at the time of surgery. Doxycycline is not indicated in cases of serious intra-abdominal infection unless the infecting flora are known to be susceptible.


Nonsuppurative nodular panniculitis (Weber-Christian disease). An unusual cause of mammary calcifications. A case of nodular panniculitis (Weber-Christian disease) with breast involvement is presented. Xeromammography demonstrated unusual calcifications in the nodules.


Elevated platelet-associated IgG in thrombotic thrombocytopenic purpura. A 41-year--old woman with thrombotic thrombocytopenic purpura (TTP) was treated with prednisone and splenectomy with complete recovery from her illness. Analysis of the patient's platelets for immunoglobulins showed abnormally elevated levels in the range of those seen in thrombocytopenic patients with systemic lupus erythematosus, immune vasculitis, and infectious mononucleosis. This finding is consistent with the concept that the immune system may play a role in the pathogenesis of TTP.


[Physiopathology and clinical aspects of the alveolar surface active system (pulmonary surfactant)]. Existing knowledge of the pulmonary alveolar surfactant system is summarised in monographic form. Particular attention is directed to its physiopathology, synthesis mechanisms, and pathology in man, as well as to the methods used into its clinical investigation. Stress is laid on the importance of the system in the direct or indirect determination of many cardiac and pneumocardiac diseases. Ways in chich deficiencies on the part of this system can be treated are critically discussed.


[Effect of actinomycin D and sibiromycin on 3H-thymidine incorporation into the early developmental stages of Nereis virens Sars]. The Nereis virens embryos at the stages of 2, 8, 16 and 32 blastomeres end of cleavage and beginning of rotation were placed in the actinomycin D or sibiromycin solutions and the effect of antibiotics on 3H-thymidine incorporation during cleavage, at the beginning of rotation and in trochophore was determined by means of autoradiography after careful washing the embryos off. Under the effect of actinomycin D the intensity of 3H-thymidine incorporation during cleavage decreased insignificantly, at the gastrula stage somewhat exceeded that in the control, and at the stages of trochophore formation decreased twice. At the later stages it approached the normal level. In the experiments with sibiromycin which proved to have more distinct inhibitory effect, the stage of trochophore formation was also found to be the most sensitive to the antibiotic.


[Laparotomy and splenectomy in Hodgkin's disease]. Explorative laparotomy and splenectomy represents the most accurate methode to recognize a lymphogranulomatous process below the diaphragm. The demonstration or exclusion of a subdiaphragmatic propagation of disease plays an essential role in therapy. Since 1973 we have performed explorative laparotomy and splenectomy in stage (I) II-III a of Hodgkin's disease. In the course of this invasive diagnostic procedures (39 primary and 12 reassessing laparotomies and splenectomies) no case of death and no persisting postoperative complications were noticed. Clinical staging was altered in 47% of cases by the procedure but in only one quarter of patients this result influenced therapeutic regimen.


Immunestimulation in cancer patients by a new synthetic compound: BM 06 002. A new synthetic compound 4-imino-1,3-diazobicyclo (3,1,0)-hexan-2-on (BM 06 002) has been shown in animal models to stimulate humoral and cell-mediated immune reactions. In a Phase I study in man a total absence of toxic side effects after intravenous injection of BM 06 002 has been demonstrated. In the present investigation in patients with advanced incurable cancer one single injection of this substance induced a significant stimulation of lymphocyte blastogenesis response to PHA and PWM. Delayed cutaneous hypersensitivity reactions, tested before and after drug application, were also found increased. According to thses findings BM 06 002 might be considered as an immune-stimulating compound.


Problems of local recurrence in patients with Ewing's sarcoma. With the increasing longevity of patients with Ewing's sarcoma not only the long term tissue effects of local treatment are important, but also the management of patients who develop local recurrent disease. Of our 42 patients with Ewing's sarcoma, 33 were treated by irradiation and 7 of them developed a recurrence. The reasons of failure to control the primary tumor are analysed in the light of present experience and guidelines for the management of the recurrence are discussed. With optimal combination therapy it is hoped, that a proportion of patients with recurrent disease can be salvaged.


Iotroxamide--a new intravenous cholangiographic agent. Comparison with iodipamide and the effect of bile salts. The maximum biliary excretion rate of iotroxamide was found to be significantly greater than that of iodipamide in bile-fistula dogs. High bile salt excretion rates had no effect on the rate of biliary excretion of either compound, but the choleresis associated with greater bile salt excretion reduced the biliary concentration of both agents. Both are potent choleretics, stimulating about 23.5 ml of bile per mmole of contrast agent excreted in bile. This obligatory coupling of the contrast agents with water as they are excreted in bile imposes a limit on the maximum concentration that can be achieved in bile. Since iotroxamide is excreted more rapidly in bile than iodipamide for any equimolar plasma concentration, it may be a superior contrast agent for intravenous cholangiography.


The lethal effect of some benzimidazoles on Taenia hydatigena in dogs. The lethal effect of some benzimidazoles on Taenia hydatigena infections in dogs have been compared. Fenbendazole, parbendazole and oxibendazole were more effective than cambendazole and thiabendazole, while coarsely ground mebendazole did not differ significantly from any of them.


Chemical meningitis related to intrathecal corticosteroid therapy. A patient developed symptomatic lymphocytic meningitis with hypoglycorrhachia after two intrathecal injections of methylprednisolone acetate. Chills, fever, and confusion occurred ten days after the second injection, and were brief in duration. There were no obvious sequelae. Hypoglycorrhachia secondary to intrathecal steroids has not been previously reported. Steroid-induced chemical meningitis should be considered in any patient who develops CNS symptoms and an abnormal CSF after receiving intrathecal steroids. Obviously, the more common causes of lymphocytic meningitis with or without hypoglycorrhachia must be excluded.


Intensive fattening of beef cattle by stall feeding on the Lilongwe Plain, Malawi. I. Type of forage and level and type of supplementation. Experiments were undertaken with Malawi zebu steers over three wet seasons to investigate the effects of feeding improved forages (zero grazed) and supplements on animal performance. The forages fed were Guinea grass and pearl millet and the supplements maize: madeya (maize bran) or maize: madeya: cottonweed cake. The daily allowance of supplement was, on a DM basis, liveweight equivalent to 0-6, 1-1 or 1-5 per cent of cattle (1973, 1974). In 1975 the supplementation treatments were nil, maize: madeya or leucaena fed at 0-6 per cent liveweight. Daily gains of steers were similar with both forages except in 1975 when those fed on pearl millet grew 19 per cent faster than those on Guinea grass. The performance of steers was increased with supplementation only where forage quality declined. The significance of the results are discussed.


[Current concept of Gougerot-Sjögren syndrome]. The Gougerot-Sjögren syndrome is giving rise to an everincreasing number of publications. Since the initial work by Gougerot in France and Sjögren in Sweden, the most important publications have been coming from the United States of America, particularly the series from the NIH at Bethesda. Since Bunim, Talal, Bloch and colleagues have taken up this topic, the conception of the disease which has become established is that of an auto-immune condition which or may not be associated with a rheumatoid polyarthritis or related diseases. It may be asked whether such a conception does in fact permit a better approach to patients suffering from the Gougerot-Sjögren syndrome. It might seem more useful to separate the exocrine syndromes from the concomittant immunitary symptoms more clearly. A further important problem is that raised by the perfection of the means of detecting the Gougerot-Sjögren syndrome. This poses a key problem : that of the borderlines of this syndrome.


[Comparative evaluation of methods for predicting fetal lung maturity based on serial amniotic fluid tests (author's transl)]. 12 pregnant females in the last trimester were subjected to serial amniocentesis. Although there was medical indication for amniocentesis the pregnancies were normal. All samples were evaluated with four different methods. We used two physical (Wilhelmy balance and foam test) and two chemical (L/S ratio densitometrically and planimetrically measured) methods. The Curves of individual pregnancies were compared with the reference values of 109 samples of amniotic liquid of uncomplicated pregnancies. Reference values for the various techniques reported in the literature are generally based on aggregate data collected from a number of pregnant females, which are then consolidated to obtain mean values for each gestational week. We found a continuous rise of all parameters, both in the reference value and in eight individual pregnancies. Besides we found a strikingly extraordinary run of the curves in four individual pregnancies. Here we recognized a rapid ascent and descent of surfactant concentration within short periods, which were not identical with the reference values. All four methods showed results with a statistical significant conformity, only the foam test showed a little lower significance.


Amniotic fluid shake test versus lecithin-sphingomyelin ratio in the antenatal prediction of respiratory distress syndrome. Surfactant content of 211 amniotic fluid samples raken between 28 and 42 weeks' gestations was determined by the shake test. Parallel with this also the lecithin/sphingomyelin (L/S) ratio was measured in 99 cases. When the test was positive no respiratory distress syndrome (RDS) occurred, while 25 RDS (53.34%) developed in 46 newborns with negative test and 8 RDS (15.38%) in 52 newborns with intermediate test. RDS was observed in all cases when the L/S ratio was below 1.5. At L/S ratios between 1.5 and 2.0, RDS appeared in 50% of the negative tests and 20% of the intermediate tests. However, when the L/S ratio was over 2.0 no RDS occured even in the case of negative tests. For the clinical praxis the positive test gives an exact information; no RDS is to be expected in such cases. In the case of a negative test, however, the authors think is necessary also to determine the L/S ratio.


Early effects of thyroid stimulating hormone (TSH) on exocytosis and endocytosis in the thyroid. The early effect (3 min) of thyroid stimulating hormone (TSH) on exocytosis-endocytosis in the rat thyroid follicle cell was investigated by electron microscopic morphometry. All rats used were pre-treated with thyroxine for 2 days prior to the experiments. In control rats, the membrane surface area of exocytotic vesicles, the only type of vesicle present in the apical part of the follicle cell, approximately equaled that of the apical plasma membrane. Intravenous administration of TSH caused a significant decrease in the membrane surface area of exocytotic vesicles by about 20% and a corresponding, significant increase in the membrane surface area of the apical plasma membrane by about 20%. Pseudopods were present in 4 of 6 TSH-injected rats examined, but the membrane surface area of these structures was only 15% of the increase in the surface area of the apical plasma membrane. The total membrane surface area analyzed was not influenced by injection of TSH. We conclude that the initial effect of TSH on the thyroid follicle cell is a re-distribution of membrane from exocytotic vesicles to the apical plasma membrane. This conclusion is in harmony with our previous observations which indicate that the (membrane-requiring) endocytotic response after TSH is regulated by the amount of membrane material added to the apical plasma membrane by exocytosis.


Characterization of T3 immunoreactivity release from thyroid gland in vitro a reflection of colloid droplet formation. T3 immunoreactivity release from the thyroid gland in vitro was shown to be increased by TSH. In the present study, we sought to determine whether the T3 immunoreactivity release is an indicator of thyroid hormone secretion or due to hormone synthesis. When thyroid glands from mice were incubated with TSH, T3 immunoreactivity release was increased in parallel with intracellular colloid droplet formation in a dose related manner. When colchicine, a known inhibitor of colloid droplet formation, was added, both T3 immunoreactivity release and colloid droplet formation were inhibited, whereas MMI, an inhibitor of hormone synthesis, failed to influence both aspects. Thus T3 immunoreactivity release as a reflection of colloid droplet formation was demonstrated. The analysis of the released immunoreactivity by Sephadex column and subsequent radioimmunoassay suggested that the T3 immunoreactivity was, to a considerable extent, due to macromolecule instead of T3 itself. The effect of I- or Li+ to inhibit thyroid hormone secretion was shown to be on the step prior to, but not subsequent to, colloid droplet formation.


Serum calcitonin in hypergastrinaemia due to achlorhydria. The serum concentrations of immunoreactive gastrin and immunoreactive calcitonin were measured in 13 fasting patients with achlorhydria and pernicious anaemia and in 10 age- and sex-matched fasting control subjects. All patients had highly elevated concentrations of gastrin in serum (1468 +/- 336 pg/ml, mean "/- SEM). The mean concentration in the controls was 35.2 +/- 6.4 pg/ml. No difference in the concentration of calcitonin was found between the pernicious anaemia patients and the controls, the levels being 0.93 +/- 0.08 and 0.89 +/- 0.03 ng/ml, respectively. Suppression of endogenous gastrin secretion in 5 of the patients by intragastric acid administration was not accompanined by any decrease in calcitonin concentration in serum. The findings suggest that chronically elevated endogenous gastrin is without influence on calcitonin secretion.


Biological activity of high dose of des-asp 1-, ileu 8-angiotensin II in man. The biological activity of high doses of des-asp 1-, ileu 8-angiotensin II (AIIIA) was studied in man. In 5 normal men an intravenous infusion of 600 ng/kg/min of AIIIA for 30 min caused a slight rise in blood pressure, a decrease in plasma renin activity and an increase in plasma aldosterone. This dose inhibited pressor and steroidogenic actions of angiotensin II infused into the same 5 normal men at a rate of 20 ng/kg/min for 30 min. These results are considerably different from our previous report using lower dose (200 ng/kg/min) of AIIIA and indicate that in man AIIIA has both agonist and antagonist activities on the peripheral arterioles as well as on the adrenal cortex.


Circadian rhythm of plasma testosterone in the male Djungarian hamster (Phodopus sungorus). A marked circadian rhythm of plasma testosterone was found in male Djungarian hamsters. Maximal values in the evening just prior to activity onset were about 12 times higher than minimum values in the early morning. The peak of serum testosterone concentration coincides with onset of oestrus in females.


Comparison of the metabolism of testosterone undecanoate and testosterone in the gastrointestinal wall of the rat in vitro and in vivo. The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T.  Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.


The effect of stressful diagnostic studies and surgery on anterior pituitary hormone release in man. The hormonal response of the anterior pituitary was studied in 10 normal males undergoing treadmill exercise testing, in 5 male patients undergoing diagnostic gastroscopy, and in 8 male patients undergoing elective surgery under general anaesthesia. Serum TSH was depressed below the baseline value at 2 and 3 h post-treadmill exercise, at 1, 2 and 3 h post-gastroscopy and from 10 min through 2 h post-surgery. Serum triiodothyronine was depressed below the baseline value at 10 min through 2 h post-surgery. Serum prolactin, growth hormone and cortisol were elevated by all three stressful procedures. Both gastroscopy and surgery resulted in an elevation of serum luteinizing hormone levels. There was no significant change in serum FSH levels in any of the three procedures. The post-stress depression in TSH levels could result from the suppressive effect at the hypothalamic-pituitary level of high serum levels of cortisol generated by the stress of the procedures.


Effect of piribedil on plasma prolactin levels in women with puerperal or pathological hyperprolactinaemia. In women with physiological puerperal hyperprolactinaemia, acute administration of Piribedil (100 mg po), a drug which stimulates dopamine receptor sites, was as effective as that of 2-Br-alpha-ergocryptine (CB 154, 5 mg po) in suppressing the elevated baseline plasma prolactin (PRL) levels. In two hyperprolactinaemic women with radiological evidence of an intrasellar pituitary tumour, Piribedil (100 mg po), in contrast to CB 154 (5 mg po), failed to modify plasma PRL levels, whereas in 3 other hyperprolactinaemic women with no radiological evidence of pituitary tumour, its effect was not clear-cut, even though it could not be differentiated from that of CB 154. These results indicate that Piribedil is an effective suppressor of plasma PRL levels in the human and suggest that its action is more evident in puerperal than in pathological hyperprolactinaemia.


Correlative study of radioreceptor assay and radioimmunoassay of serum growth hormone in children: normal children and HGH-treated pituitary dwarfs. A sensitive and reproducible radioreceptor assay (RRA) for human growth hormone (HGH) is described. It allows the evaluation of HGH concentrations as low as 2 ng/ml. It has a limited cross-reactivity with human prolactin, which does not interfere at physiological levels in children. Comparison of the results with those of radioimmunoassay (RIA) showed no discrepancies in the serum of normal children before and after stimulation tests for GH (mean RRA/RIA ratio 1.03 +/- SEM 0.04, range 0.75 to 1.65) nor in the serum from hypopituitary dwarfs during the 12 h following an im injection of 6 mg of HGH (mean RRA/RIA ratio 1.05 +/- 0.04, range 0.84 to 1.28). It is concluded that receptoractivity of HGH is parallel to its immunoreactivity in normal children and in hypopituitary patients clinical grade HGH.


Studies on circadian variations of plasma TSH, thyroxine and triiodothyronine in man. To evaluate the existence of circadian variations in thyroid hormone and TSH levels, blood was drawn every 20 min for 24 h in four and for 14 h in one volunteer. Hormones were measured by sensitive radioimmunoassays. TSH: A diurnal rhythmicity could be demonstrated with peaks from 8 p.m. to 2 a.m and a nadir from 7 a.m. to 2 p.m. Superimposed on the diurnal rhythm multiple shortlived fluctuations were observed. Thyroxine: Pooled data showed peak values from 8 a.m. to 12 a.m. and lowest levels from 11 p.m. to 3 a.m. Again, shortlived fluctuations were superimposed on the diurnal rhythm in all instances. Triiodothyronine: Hormone levels were highest from 7 a.m. to 1 p.m. and lowest from 11 p.m. to 3 a.m. Fluctuations in T3 levels were less marked than those of T4. Diurnal variations in hormone levels can be demonstrated in most, but not in all instances. Fluctuations are minor and do not exceed the normal range. Therefore these changes are of no relevance in routine testing of these hormones.


The effect of ovarian steroids on hypothalamic norepinephrine neuronal activity. The concentration of norepinephrine and the apparent turnover of norepinephrine in the hypothalamus was studied in castrated rats and after the injection of ovarian steroids. Both parameters were found to vary not only with the hormone treatment, but also with the time of the day. Norepinephrine concentration in the anterior hypothalamus of castrated male and female rats was significantly higher in the afternoon than in the morning, but no statistical difference was observed in the concentration of norepinephrine in the posterior hypothalamus. Three days after the injection of a single dose of 20 microgram oestradiol benzoate, norepinephrine concentration and apparent turnover were found with decreased significant values in the anterior hypothalamus of castrated females, killed in the afternoon. Progesterone 2 mg injected three days after the priming dose of oestradiol benzoate, produced 4 h later in the afternoon a significant rise in norepinephrine concentration and apparent turnover. These results suggest that the apparent turnover of hypothalamic norepinephrine in the afternoon is reduced by oestrogen and increased by oestrogen plus progesterone.


Evaluation of propranolol-glucagon test. A propranolol-glucagon test was evaluated in 24 control normal children, 21 pituitary dwarfs, 15 patients with constitutional short stature, 2 with chromosome aberration and 4 with miscellaneous diseases. The dose of glucagon enough for the stimulation of human growth hormone (HGH) secretion is more than 20 microgram/kg of body weight. During the test in the control subjects the serum HGH level increased from 2.3 +/- 1.2 ng/ml to a maximum level of 30.0 +/- 15.1 ng/ml, when 10 mg propranolol, regardless of body weight and 30 microgram glucagon per kg of body weight are given. The dose of propranolol administered ranged from 0.2 to 1.0 mg/kg of body weight in normal children studied. Serum 11-OHCS also increased significantly from 14.5 +/- 11.2 microgram/100 ml to 30.1 +/- 15.5 microgram/100 ml (P less than 0.01). There was no difference in the maximum level of urinary total catecholamines in propranolol-glucagon test between 7 pituitary dwarfs and 7 control subjects. The mechanism of HGH response to propranolol-glucagon administration is unknown, but propranolol-glucagon administration is a sensitive and reliable provocative test for HGH secretion, since false negative response of HGH are not observed in patients with non-pituitary disease.


Stimulating action of sulpiride and pimozide on prolactin release. Effect on bromocriptine, L-dopa and metergoline administration. In order to evaluate the mechanism of action of metergoline, an antiserotonin agent, the effect of pre-treatment with metergoline on prolactin (PRL) release induced by sulpiride was compared to that obtained after bromocriptine administration in normal subjects. In addition, the metergoline effect on PRL release induced by pimozide, specific dopamine receptor blocking agent, was compared to that obtained with L-dopa. Metergoline administration resulted in definite decrease in plasma PRL in all subjects; however, metergoline did not block, differently from bromocriptine, the PRL release induced by sulpiride. On the contrary, metergoline, like L-dopa, inhibited PRL release induced by pimozide pre-treatment. These results raise the possibility that metergoline does not act as an antiserotonin agent; its antilactogenic effect observed under basal conditions may be dependent on different mechanisms of action.


Failure of sodium loading or deficiency to affect plasma prolactin in the male rat. The relation between plasma prolactin (PRL) and sodium metabolism was studied in adult male rats. During the experiments attention was given to the avoidance of stress. Cannulated rats were infused with 2.5 ml 5% NaCl over a 40 min period. Plasma PRL did not change during or up to 2 h after this infusion. Other rats were subjected to a sodium deficient diet for 3 weeks. This treatment which induced a marked rise in plasma aldosterone, did not cause a change in plasma PRL. It is concluded that PRL does not have an important role in the regulation of sodium balance.


Thyroid vascularity--documentation of the iodide effect in thyrotoxicosis. Thyroid vascularity was measured in 101 thyrotoxic patients by analysis of 99mTc pertechnetate thyroid flow studies obtained with a gamma camera--minicomputer system. The diffusely hyperplastic goitres tended to have higher vascularity than the toxic multinodular goitres, and many of the solitary toxic nodules had vascularity results within normal limits. Potassium iodide therapy, 60 mg b.d. for 10-14 days results in a dramatic reduction in thyroid vascularity in diffuse thyroid hyperplasia and toxic multinodular goitre but the effect on toxic nodules was marginal.


Lactate concentrations in pre-ovulatory follicles of pro-oestrous rats before and after onset of oocyte maturation. Lactate concentrations were determined in pre-ovulatory follicles of rats at pro-oestrus before and after onset of oocyte maturation. It appeared that high concentrations prevail before and after the time of the expected LH surge (27 mM). The level in serum was about 5 mM. Explanted oocytes obtained from pre-puberal rats and surrounded by cumulus cells, matured in the presence of 20 mM lactate as sole exogenous energy source. It is argued that oxygen may be the limiting factor suppressing oocyte maturation in vivo.


A radioligand receptorassay for serum HCG. A radioligand receptorassay system is described for the measurement of human choriogonadotrophin (HCG) in serum, using 600-1600 X g fractions of homogenates of superovulating rat ovaries. The method is specific for HCG and lutrophin (LH), with a detection limit of 3.5 mIU HCG. The values obtained in the dilutions of pregnancy sera paralleled the standard curve up to 20 microliter, and no non-specific effects were found with this amount of serum. The potency ratio R/I, measured in normal pregnancy sera by radioligand receptorassay and radioimmunoassay, varied between 1.1 and 3.2. No relationship was found between the stage of pregnancy and the R/I ratio.


Relation between sex hormone binding globulin and D-norgestrel levels in plasma. In order to investigate the effect of changes in sex hormone binding globulin (SHBG) levels on d-norgestrel (d-Ng) levels in plasma, the plasma levels of SHBG and d-Ng were studied during one treatment cycle in 6 women on oral contraceptives containing d-Ng and ethinyloestradiol (EOE2) and in 3 women using subcutaneous silastic rods containing d-Ng concomitantly taking EOe2 for three weeks. A significant positive correlation between the SHBG and d-Ng levels was found in 7 of the 9 subjects studied. The results provide evidence for an in vivo binding of d-Ng to SHBG, a SHBG influence on the metabolic clearance rate of d-Ng and consequently a dependence of the plasma levels of d-Ng on the SHBG concentrations in the plasma. These findings support the concept that the clinically and biochemically observed anti-oestrogenic/androgenic effects observed in women on d-Ng containing medication are due to a displacement of testosterone from SHBG by d-Ng.


Effect on intraocular pressure of retrobular injection of xylocaine with and without adrenaline. The changes in IOP were registered in two groups, each comprising 30 patients, after a retrobulbar injection of Xylocaine and Xylocaine-adrenaline respectively. No significant difference between the mean values of the initial pressures and the IOP during the following ten min could be proved in either of the groups, but in several individual cases there was a considerable and unpredictable change in IOP following the injection. After ten min this effect was still often present but less pronounced. The change in IOP was significantly greater when adrenaline was used. As a result of these findings the authors have been inclined to cease using adrenaline in retrobulbar anaesthesia for intraocular surgery of short duration.


Methodological aspects of tear flow determination by means of a radioactive tracer. Theoretical considerations on a simplified biological system representing the tear pathways lead to the assumption of an exponential pattern of elimination of tracer substances from the conjunctival sac. The tracer used in the present study was technetium, Tc99m, as sodium pertechnetate. The detection system consisted of a gamma camera coupled to a digital system, a minicomputer and a magnetic tape unit. After instillation of 10 microliter normal saline solution containing Tc99m the decay of activity was followed by means of an activity-time function curve to which exponential curves were approximated by the computer. As a parameter for tear flow the fractional turnover rate was calculated from 7 to 15 min after instillation. An initial faster elimination was found in the first 7 min following instillation. Corrections for background radiation, evaporation of water and transconjunctival transport of Tc99m were estimated.


Normal values in clinical electrooculography. IV. Analysis of two dimensionless EOG parameters and their relation to other variables. Two EOG parameters - The Arden ratio (A) and an expression devised by Gliem (G) - from a sample of normal human subjects are studied. Their relations to the EOG potential and time parameters and to sex, age, pupillary diameter, degree of iris pigmentation, refractive error and axial length, ocular protrusion and interpupillary distance were assessed. Right eye and left eye distributions were congruent, although individual differences were sometimes appreciable, especially in the case of G. The two ratios were positively correlated and both showed a negative correlation to the interval between the dark trough and the light peak. Correlations to the EOG potential parameters, especially the light induced potential rise of the dark adapted eye, were also established. In the case of A, a higher level was disclosed in the male half of the sample. A negative age correlation, predominant in the female part of the sample, characterized both ratios. The two ratios were positively correlated to the pupil diameter, negatively correlated to the degree of refractive errror, and positively correlated to the degree of ocular protrusion. The consequences for the clinical EOG test are discussed, and it is concluded that the present EOG procedure is a qualitative rather than a quantitative test.


Continuous recording of the intraocular pressure in human and rabbit eyes with a simple applanating suction cup. A suction cup has been devised to fit the periphery of the cornea and applanate its central part. A slow, continuous saline infusion entering through a central opening forms a disc of fluid between applanating and applanated surface in which the pressure (Pcup) is followed by a conventional transducer. The saline leaves the periphery of the cup via a hanging tube creating a suction pressure of approximately 15 mmHg, which keeps the cup on the cornea. In human cadaver eyes the relation between intraocular pressure (Po) and Pcup was Po = 0.80 X Pcup - 2.3 (mmHg), r = 0.9986. In enucleated rabbit eyes: Po = 0.94 X Pcup - 0.1 (mmHg), r = 0.9996. Thus, with appropriate calibration of the recorder, the cup functions both accurately and linearly. The relationships were virtually uninfluenced by large changes in both the rate of suction and the inflow rate of saline. When measuring on eyes of patients, the cup was atraumatic and gave an excellent dynamic response.


Model computation of the effect of arbitrary variations in aqueous inflow, outflow conductance, ocular rigidity and episcleral vein pressure on ocular pressure. Model calculations of the time course of the intraocular pressure are performed in cases where the four determinants mentioned in the title vary, singly or simultaneously, according to specified time functions. Assumptions are 1) that the outflow of the aqueous humor is proportional to the driving pressure, and 2) that the intraocular pressure and volume are  related to each other as described by Friedenwald. The mathematical solution if numerical and involves the repetition of the same calculatory step process. It is rendered probable that the maximal inhibitory effect of acetazolamide on the secretion  of  aqueous humour is reached in less than one minute after the drug has reached the receptors. A programmable calculator with 224 storage locations is used, the programs are given.


Relative contents of sodium, potassium, water and dry matter in human senile cataractous lenses in relation to anterior capsular/subcapsular opacity. In 49 human senile cataractous lenses the sodium and potassium concentrations of the lens water as well as the water and dry weight percentages were examined. It was found justifiable to classify the lenses into three categories on the basis of correlated biomicroscopic and biochemical findings: 1. Immature cataractous lenses without anterior capsular/subcapsular opacity (ac-sco) were characterized by low CNaL+, high CKL+ and low sums of CNaL++CKL+. 2. Immature cataractous lenses with ac-sco were characterized by intermediate value of CNaL+ and CKL+, as well as high sums of CNAL++CKL+. 3. Totally opaque lenses (these lenses had 80-100% of ac-sco) were characterized by high CNaL+, low CKL+, high sums of CNaL++CKL+, high water, and low dry weight percentages. It was found that in immature cataractous lenses increasing extension of ac-sco was correlated to increasing CNAL+ and increasing ratios of CNAL+/CNAA+ as well as to decreasing CKL+ and decreasing ratios of CKL+/CKA+. The sums of CNaL++CKA+ increased. There was a correlation of the extent of ac=sco to the water and dry weight percentages of the immature senile cataractous lenses with ac-sco, viz. a negative correlation for water and a positive one for the dry weight. However, these latter two correlations may be due to chance significances, the level of significance being only greater than P greater than 0.02 in both instances. Lenses which were estimated to have larger than or equal to 30% of ac-sco were found to be more opaque than lenses with less than or equal to 25% of ac-sco.


Placoid pigment epitheliopathy presenting as an anterior uveitis. A case report. A young woman with acute posterior multifocal placoid epitheliopathy originally presented with signs and symptoms of an anterior uveitis. Prior to the eye condition the patient had experienced headaches and malaise with some muscle and joint tenderness, and had been treated with penicillin because of a dental infection. The clinical and fluorescein angiographic findings are presented. The evidence supports the concept of a primary vascular disturbance of the choriocapillaris with secondary involvement of the retinal pigment epithelium.


Notes on the distribution of pseudo-exfoliation material with particular reference to the uveoscleral route of aqueous humour. The distribution of pseudo-exfoliation material along the uveoscleral route of aqueous humour has been studied by electron microscopy. It turned out that such material is present only in the very first part of this exit pathway, i.e. in the innermost zone of the connective tissue bordering the anterior chamber angle. No pseudo-exfoliation material was observed between the ciliary muscle cells, in the suprachoroidal space or in the sclera. It is concluded that transport of pseudo-exfoliation material by flow of aqueous humour through the uveoscleral route to the bulbar and palpebral conjunctiva is improbable, and accordingly the pseudo-exfoliation material found in extrascleral tissue most likely arises in loco.


Demonstration of peripheral hemiopic border steps by static perimetry. 10 normal eyes were examined by static perimetry along a horizontal line 60 degrees below the fixation point. All showed a greater sensitivity in the temporal hemifield. The study confirmed the previously reported existence of a step and indicated a greater threshold specifically at the hemiopic border.


Polysaccharide coating of human corneal endothelium. Electron microscopy revealed the presence of a 600-1500 A thick layer of polysaccharide on the surface of human corneal endothelial cells. The surface layer was visualized by combined fixation and staining in a mixture of ruthenium red and osmium tetroxide. The coating material was stable for at least 39 h post mortem and was retained on disintegrating cells.


Computer test logics for automatic perimetry. Using an automatic computerized perimeter developed by Heijl & Krakau (1975b) three different perimetric test logics, one simple (I) and two more complicated and time-consuming (II & III) were investigated in practical experiments on healthy normal test subjects and patients and in computer simulated tests. The patients either had a verified diagnosis of glaucoma or glaucoma was suspected. The best consistency in measured thresholds was obtained with test logic II, in which an averaging procedure is used. The variation of the results was larger in pathological than in normal visual fields. All test logics investigated readily detected the pathological field defects, but blind spots could easier pass unrecognized with the simplest logic than with the other two logics. The conclusion is drawn that a simple test logic can be used for perimetry in glaucoma suspects if no visual field defect has previously been documented. For the follow-up of pathological fields a fairly complicated test logic, e.g. using averaging, is preferable.


A note of fixation during perimetry.

A note of fixation during perimetry. Small eye movements in the direction of the disappearing stimulus can be observed at kinetic perimetry when the test object enters a scotomatous area. These may be responsible for the fact that several field defects, missed at routine manual perimetry, are spotted at automatic perimetry. In the latter case the patient cannot predict the position of next test light, since these are illuminated at random, whereas at kinetic perimetry they are exposed in systematic order. By using two specially designed logics in automatic perimetry, it was shown that there may be a reduction of the scotoma size if the lights are exposed in an ordered sequence. This effect is avoided by using a logic with randomly exposed stimuli. It is most likely that the difference can be attributed to "malfixation".


Pseudodoubling of the optic disc. A fluorescein angiographic study of a case with coloboma. In a woman, aged 45, with presbyopic complaints routine examination revealed pseudodoubling of the right optic disc and a colobomatous defect of the left eye. The former was studied by fluorescein angiography. The differentiation between true doubling and pseudodoubling of the optic disc is discussed.


Passage of digoxin into cerebrospinal fluid in man. The passage of digoxin into the cerebrospinal fluid (CSF) was studied in 8 infants on maintenance therapy with digoxin, 11 adult patients on long-term digoxin therapy, and 15 patients, previously non-digitalized, who were given 0.5 mg digoxin orally 1 hr to 12 hrs prior to lumbar puncture. Digoxin in the serum and CSF was determined by radioimmunoassay. In the infants a mean serum concentration of 1.5 ng/ml (range 0.7-2.3 ng/ml) was found, and a simultaneous mean CSF concentration of 0.5 ng/ml (range 0.3-1.1 ng/ml). In the adults on long-term therapy, the corresponding figures were 1.1 ng/ml (range 0.5-2.2 ng/ml) and 0.3 ng/ml (range 0-0.6 ng/ml). Among the 15 patients given a single oral dose of digoxin, detectable CSF concentrations (0.2-0.3 ng/ml) were found in five, 1-12 hrs after the administration of the drug. In three paediatric patients with hydrocephalus (3 months-5 years) digoxin therapy was started as an attempt to decrease CSF production. In these patients, the production of CSF was reduced by 17, 25 and 30%, respectively.


Guanethidine induced sympathectomy in the adult rat. I. Functional effects following subacute administration. Guanethidine sulphate 5 and 40 mg/kg was administered intraperitoneally to adult rats for 4, 8, 14, and 28 days followed by discontinuation for 1 day, after administration for 28 days and additionally for 8, 14, 29, and 60 days. Under chloralose-urethane anaesthesia the mean arterial blood pressure and the mean heart rate were determined and the response of these parameters to intravenous noradrenaline 3-1600 ng was recorded. The blood pressure was not significantly changed after guanethidine 5 mg/kg, but lowered by 40 mg/kg, the decrease being reversible on discontinuation. The response of both parameters to noradrenaline was increased by guanethidine depending on the dose. The hypersensitivity was partly reversible on discontinuation, but a significantly increased sensitivity of the heart rate to noradrenaline was observed 60 days after discontinuation of guanethidine 40 mg/kg for 28 days. Histologically a profound loss of nerve cells of the superior cervical ganglion was observed following guanethidine 40 mg/kg, whereas no change was observed after 5 mg/kg. The present investigation has demonstrated that guanethidine 5 mg/kg does not induce histological or permanent haemodynamic changes, whereas 40 mg/kg for 28 days result in an incomplete sympathectomy accompanied by a partially irreversible hypersensitivity to noradrenaline. There is no simple relation between the loss of ganglion cells and the haemodynamic changes, and hence the hypersensitivity to noradrenaline is only in part due to the destruction of the postganglionic sympathetic neurone obtained by long term administration of large doses of guanethidine.


Guanethidine induced sympathectomy in the adult rat. II. Functional effects following chronic administration. Guanethidine sulphate in doses of 5 and 40 mg/kg was administered intraperitoneally to adult rats daily for three months followed by discontinuation of administration for one day or three months. Following guanethidine 40 mg/kg a loss of approximately 95% of the nerve cells of the superior cervical ganglion was observed. No changes were observed after 5 mg/kg. The average mean arterial blood pressure (measured under chloralose-urethane anaesthesia) was lowered by 33 and 54 mmHg by guanethidine 40 mg/kg for three months followed by discontinuation for one day and three months respectively. The heart rate was unchanged. Guanethidine 5 mg/kg did not change any of these parameters. The increase in blood pressure and heart rate caused by intravenously administered noradrenaline was greatly enhanced following guanethidine 40 mg/kg, whereas only small changes were observed following 5 mg/kg. Following discontinuation for one day of 40 mg/kg for three months the potency ratios for the mean arterial blood pressure and the mean heart rate were 31 and 21 respectively, after discontinuation for three months 44 and 17 respectively. The potency ratios following guanethidine 5 mg/kg were 1.5 to 2.0. No changes were observed in the weight of the suprarenal glands following guanethidine. The present investigation has demonstrated an almost total chemical sympathectomy by guanethidine 40 mg/kg for three months and a persistent hypersensitivity to noradrenaline even after discontinuation of medication for three months.


Release of platelet 5-hydroxytryptamine by some anorexic and other sympathomimetics and their acetyl derivatives. The effect on 5-hydroxytryptamine release from rabbit platelets to plasma of ten known sympathomimetic or anorectic phenethylamines and eight N- or O-acetyl derivatives of these substances were studied in order to find possible structure-action relationships and a possible correlation to the pulmonary hypertension inducing ability of some anorexigens. Among the mainly indirectly acting sympathomimetics amphetamine and ephedrine showed a similar high 5HT-releasing effect. Tyramine was slightly weaker, while the direct acting phenylephrine (metaoxedrine) and orciprenaline were much weaker. Acetylation increased the 5HT releasing effect of amphetamine, ephedrine and tyramine but decreased this effect of phenylephrine and orciprenaline. Among the anorectic phenethylamines the 5HT-releasing effect decreased in the following order, aminorex, amphetamine, clophorex, chlorphentermine, diethylpropion (amphepramon), phentermine. With regard to aminorex, which is a releaser of platelet 5HT and an inhibitor of both MAO activity and 5HT uptake in pulmonary tissue, it seems possible that the pulmonary hypertension can be caused by high concentration of free 5HT.


Azidocillin and ampicillin concentrations in middle ear effusion. The penetration of azidocillin and ampicillin into the middle ear effusion after oral administration was studied and compared with blood levels of the drugs. In acute otitis media one hour after a single oral dose of azidocillin (15 mg/kg) 1.56 +/- 0.44 microgram/ml of the drug was found in the effusion fluid; after 2 hours the fluid contained 3.21 +/- 0.87 microgram/ml and after 12 hours,0.84 +/- 0.13 microgram/ml. The concentrations of ampicillin were 1.15 +/- 0.23 microgram/ml after one hour, 2.17 +/- 0.46 microgram/ml after 2 hours and 1.09 +/- 0.22 microgram/ml after 8 hours following a single oral dose of 10 mg/kg. Both drugs stay longer in the middle ear secretion than in the blood. This persistence supports the administration of azidocillin twice daily in acute otitis media. In contrast, the penetration of the drugs into the middle ear effusion fluid was poor in secretory otitis media, where the levels of the drugs were significantly lower.


Metabolism of 14C-antipyrine in suspensions of isolated rat liver cells. Suspensions of liver cells isolated from perfused rat livers were incubated with antipyrine-N-methyl-14C. Antipyrine was eliminated by first-order kinetics during incubations for 3 hours with primary suspensions (parenchymal cells + non-parenchymal cells) and suspensions of purified parenchymal cells. Antipyrine concentrations were unchanged when incubated with suspensions of non-parenchymal cells, dead cells or medium only. At the end of incubation period, 4-OH-antipyrine and 3-CH2OH-antipyrine were detected mainly as the glucuronide or sulphate conjugates, and evidence for the N-demethylation of antipyrine was also obtained. Half-lives for elimination of antipyrine in primary cell suspensions were not significantly different from the half-lives measured in parenchymal cell suspensions. This finding together with the lack of metabolism of antipyrine found in non-parenchymal cell suspensions suggest that oxidation and conjugation of antipyrine is mainly confined to the parenchymal cells. There was significant inhibition of antipyrine metabolism in primary suspensions by phenylbutazone (1.6 X 10(-3)M), dexamethasone (2 X 10(-4)M) and ethanol (1.3 X 10(-2)M, 0.75%). We suggest that the use of primary suspensions of isolated rat liver cells provide a rapid and simple method for the study of factors influencing drug metabolism in the liver.


Distribution and fate of the insect repellent 14C-N, N-diethyl-m-toluamide in the animal body. II. Distribution and excretion after cutaneous application. The tissue distribution of 14C-labelled N,N-diethyl-m-toluamide (DEET), a widely used mosquito repellent, was studied by means of whole-body autoradiography after cutaneous application to mice. The early picture was very similar to that previously observed after intravenous injection of the substance, with high concentration of radioactivity mainly in the lacrimal gland, liver, bile, intestinal contents, kidney, urine, and nasal mucosa. Urinary excretion in mice was highest early after application whereas in a human volunteer maximal excretion appeared only after several hours. In mice a low but significant excretion persisted throughout the observation time of one month, probably emanating from the considerable amount of radioactivity remaining in the smeared skin area, as observed both autoradiographically and by means of quantitative measurements.


Measurements of the air conditioning capacity of the nose during normal and pathological conditions and pharmacological influence. A simple method is introduced for measuring the air conditioning capacity of the nose. A flow of 8 1/min dry air is introduced by a catheter into the nasopharynx, while 5 1/min is sucked out from the investigated nasal cavity through a psychrometer. The additional 3 1/min passes down into the pharynx, thus reducing the intermingling with expiratory air. By using CO2 as a tracer, this error was found to be maximally 15% and often about 1%. The three different enthalpy factors: increase in enthalpy of dry air, vaporization, and increase in enthalpy of water vapour, were calculated separately and the vaporization was found to be the dominant factor. The calculated total supply of humidity showed that the method presented causes at least a slight stress on the humidifying capacity. Pharmacological studies have shown that subcutaneously injected atropine decreased the total enthalpy and that of water vapour, while nasal administration of oximetazoline also decreased the total enthalpy. Nasal administration of homatropine or pilocarpine had no effect on the air conditioning. In comparison with normal subjects, those with vasomotor rhinitis had an increased enthalpy of the air, while the same enthalpy factor was reduced in cases with atrophic rhinitis. Laryngectomized patients had no significant difference in the air conditioning capacity of the nose in relation to normal subjects, while patients operated with partial maxillectomy had a considerable reduction in vaporization and total enthalpy.


Carbamazepine: placental transport, tissue concentrations in foetus and newborn, and level in milk. The pharmacokinetics of carbamazepine were studied during pregnancy and early childhood by investigating the extent of its placental penetration and its distribution in the foetal and neonatal tissues at autopsy. In foetuses the liver and kidney contained high levels of carbamazepine, whereas brain and lungs had low values. Carbamazepine-10,11-epoxide was also detected in the foetal circulation. At autopsy material, carbamazepine was localized mostly in the cerebral cortex, heart, liver and kidney. The concentration of carbamazepine in the milk was found to be 60 per cent of the respective plasma value.


Simultaneous determination of furosemide and two of its possible metabolites in biological fluids. By the means of thin-layer chromatography (TLC) prior to fluorometry it was possible to determine furosemide (F) in plasma and urine with improved specificity. Antranilic acid (A) and 4-chlor-5-sulphamoyl-antranilic acid (CSA) could be determined simultaneously with F in plasma. In urine, only F and A could be determined quantitatively by this method. The sensitivity is 0.1 microgram/ml for F and 0.15-0.20 microgram/ml for A and CSA. By means of TLC prior to fluorometry the blank value for F was reduced in normal subjects and in different groups of patients, and its diurnal variation was eliminated. The average values of the plasma concentrations of F after the intravenous injection of 40 mg into 12 normal subjects were at all times found to be lower by the TLC method than by the fluorometric method without TLC. A higher plasma clearance and a lower volume of distribution were found for F when the values obtained by the TLC method were used for the calculation.


Inducible aldehyde dehydrogenases in the hepatic cytosol of the rat. Rats of the Wistar/Af/Han/Mol/(Han 67) strain have previously been shown to respond in a variable way to phenobarbital treatment, as far as the induction of aldehyde dehydrogenase activity is concerned (Marselos 1976). This biochemical property is genetically determined and concerns the high-Km aldehyde dehydrogenase of the hepatic cytosol. In this study, administration of phenobarbital (1 mg/mo of drinking water, for 1 week) produces a uniform induction of aldehyde dehydrogenase in all rats, when measured with micromolar substrate concentration. The inducible low-Km enzyme of the cytosol is not genetically determined like the high-Km enzyme, and shows a wide specificity for aliphatic as well as for aromatic aldehydes. Despite the inducibility of the cytosolic enzymes, no alterations are found in the mitochondrial aldehyde dehydrogenase activities after phenobarbital treatment. The oxidation of D-glucuronolactone takes place only in the cytosol, and seems to be dependent on the low-Km aldehyde dehydrogenase. This is consistent with NMR studies, which showed that a very minimal amount of D-glucuronolactone is in aldehyde form under the measurement conditions usually applied. Further, the oxidation of D-glucuronolactone is also enhanced by phenobarbital in all rats without a genetic predisposition, and its dose-response curve is very similar to that of the low-Km aldehyde dehydrogenase.


Simultaneous determination of codeine and morphine in biological samples by gas chromatography with electron capture detection. A sensitive gas chromatographic method for the simultaneous determination of codeine and morphine in plasma and brain samples is described. The method involves solvent extraction of the compounds from plasma, derivatization with pentafluoropropionic anhydride and subsequent separation on a 3% OV-17 column. The quantification is performed with electron capture detection. The sensitivity of the method (0.75 ng of morphine and 7.5 ng of codeine in a sample) makes it especially useful for pharmacokinetic investigations. The method was successfully applied to determine the time course of codeine and its metabolite morphine after intravenous administration of codeine to the rat.


Compensated low-dose 131I therapy of Graves' disease. To minimize the high rate of residual thyrotoxicosis encountered in low-dose 131I therapy of Graves' disease, we have treated 62 patients with a low-dose 131I protocol that includes a compensation for thyroid size. Dose varied between 40 muCi retained/g for glands of normal size to 100 muCi/g for glands of 100 g or greater. Mean dose was 51.9 muCi/g. At 1 year after therapy, 66.1% of subjects were euthyroid, 9.7% hypothyroid, and 24.2% hyperthyroid, a significant improvement (P less than 0.01) over our previous experience using 50 muCi/g independent of gland size. Several factors, other than 131I dose, which might influence the outcome of therapy, were investigated. Initial free thyroxine index observed before therapy was found to have prognostic significance. Hypothyroidism developed only in patients having an initial free thyroxine index of 22.5 or less (about 2.5 times the upper limit of normal in our laboratory).


[Obtaining 14-oxycarminomycin and a study of its antitumor activity]. The authors obtained  14-oxykarminomycin by alkaline hydrolysis of 14-bromokarminomycin. On two-fold  intravenous administration to mice with lymphosarcoma, strain L10-1, 14-oxycarminomycin showed the same toxicity as karminomycin. The preparation had the same selective antitumor activity as karminomycin.


[Detection of allergy to antibiotics in dermatology--venereology practice]. A total of 205 stationary patients with and without drug disease were examined with the purpose of diagnosing allergy to the widely used antibiotics. The reaction of leucocytosis was used in the studies and the antibiotic concentration was increased up to 1 gamma/ml. Sufficiently high specificity of the reaction for diagnosis of the medicamentous allergy was determined. Increased sensitivity was most frequent to penicillins. Participation of biologically active substances, such as heparin and histamine in exacerbation reaction in syphilitic patients treated with penicillin was found. The most pronounced increase in the levels of these substances in the blood of the patients was observed 6 hours after the beginning of the treatment without any connection without any connection with the clinical signs of the exacerbation reaction.


[Food habits].

[Food habits]. This descriptive study presents a series of factors that can influence food habits, being the educational level the most important independent variable. The sample included families that had infants (1-2 years) and preschool children (2-6 years). These families belonged to all socio-economic levels, not being well represented the very high and the very low levels. The results are presented individually by food groups and by a sequence of factors that could influence the food consumption behaviour. From the results one can observe that there is a great need of nutrition education to affirm and modify some habits and create others. This could be of great value for the general population.


Immunosuppression by human placenta lactogen (HPL) and the pregnancy-specific beta 1-glycoprotein (SP-1). Inhibition of mitogen-induced lymphocyte transformation. The in vitro effect of human placental lactogen (HPL) and the gravidity-specific beta1-Glycoprotein (SP-1) on the lymphocyte transformation was investigated in 20 healthy women. It was shown that simultaneous incubation of the lymphocytes with HPL or SP-1 together with PHA has no influence on the incorporation rate of H3-Thymidine. When the fetal calf serum (FCS) in the lymphocyte cultures was substituted by a 3% human albumin-solution, there was a reduction of the incorporation rate of the radioactive nucleic acid precursors to 20%, as compared to the controls with FCS. After addition of HPL and SP-1 to the cultures there was a further dosis dependent decrease of the incorporation rate. When lymphocytes were preincubated with the proteins for 24 h, there was a marked reduction of the blastogenesis after additon of PHA, HPL and SP-1 under these conditions had a immunosuppressive effect on the lymphocyte transformation.


Chevalier Jackson Lecture: In quest of the prevention of hyaline membrane disease. Hyaline membrane disease or respiratory distress syndrome of prematurely born infants is more common in males, in Caucasians, has a familial predisposition, and is associated with maternal diabetes and delivery by cesarean section before the onset of labor. Now known to be the sequel of surfactant deficiency, it can be predicted prenatally by assay of amniotic liquid for surface active materials produced by the fetal lung. Deficiency of adequate surfactant synthesis or secretion can result in low levels of lecithins and other phospholipids in amniotic liquid. Lung maturation can result in low levels of lecithins and other phospholipids in amniotic liquid. Lung maturation can be accelerated if labor or elective delivery can be deferred at least 24 hours. Glucocorticoids given to the mother cross the placenta and enter fetal lung tissues; specific receptors exist in the lung which permit glucocorticoids to promote cell differentiation and surfactant synthesis precociously. Clinical trials support the efficacy and lack of short-term toxicity of glucocorticoids in human pregnancy after 28 weeks gestation in the event of premature onset of labor. Maternal toxemia, infection or illness which may be aggravated by glucocorticoids may contraindicate prenatal treatment. Postnatally endogenous glucocorticoids accelerate lung maturation, and further administration confers no additional benefit.


[Decidualisation of the endometrial stromal cell. An electron microscopic study (author's transl)]. The fine structural changes of the endometrial stromal cell from late secretory phase up to full developed decidua cell have been investigated by means of electron microscope. During decidual transformation the cell volume, the assortment of cytoplasmic organelles and the mode of intercellular attachments undergo characteristic alterations. These alterations reflect an adaptation on new cellular functions. In contrast to the structural organization, which is transformed continuosly, the encymatic cell pattern exerts a step wise gradual transformation, since new encymatic capacities can only arise after their funtional structures have been established. To the most important functions of decidua cells and their prestages belong secretory and endocrine activities. Precollagen fibrills represent a specific secretory product of the stroma reticulum cells. The active involvement of the full differentiated decidua cells in steroid metabolism is indicated by characteristic transformation of the cytoplasmic organization concomittantly to the appearance of intracellular steroid dehydrogenase activities. So-called karyosoma could be demonstrated within the nuclei of postovulatory stromal reticulum cells as in decidua cells. Similar nuclear differentiations have been observed in various target cells of steroid hormones. They possibly are structural manifestations of the hormonal interaction with the nuclear DNA.


[Studies on the dependence of intrafollicular pressure on the pressure in the intraovarian-vascular-system and tissue, carried out in vitro on human ovaries (author's transl)]. The intrafollicular, intraovarian and intraarterial hydrostatic pressures were measured in vitro on human ovaries in the vollicular ripening phase. It has been established that in the vascular system as well as in the intraovarian tissues pressure variations occur spontaneously. Thus for example under, the influence of epinephrine, norepinephrine, prostaglandine F2 alpha and oxytocine, the tonicity of the vascular system increases and does so the number of spontaneous contractions rather noticeably, particularly under the influence of prostaglandine F2alpha, and under the various catecholamines an increase of frequency and amplitude has been observed. Any increase of pressure in the intraovarian vascular system and tissues will effect all the follicles not yet in the preovulatorian phase, in which they cause a similar pressure increase. However, follicles imminently preovulatorian have not shown such pressure increase because the increase of the "liquor folliculi" runs parallel to the increasing elasticity of the follicle walls. The findings are discussed in this article with a particular view of the biophysical aspects of ovulation.


Ethnicity and adaptation to climacterium. An investigation was made into the menopausal symptoms and attitudes of 1,148 Israeli women of five different ethnic origins. The results show that, while some of the somatic menopausal symptoms are independent of ethnic origin, psychic and psychosomatic symptoms are more closely associated with this variable. Similarly, the general health of menopausal women also varies with cultural origin. This variation is shown to correlate with the psychic and psychosomatic symptomatology of the climacterium. This study underlines the necessity of a multi-factorial, biological, sociological, psychological and anthropological approach to problems of menopause.


[Thelarche: psychosocial aspects for gynaecology. Psychometric investigation in 533 women (author's transl)]. The psychosomatic and psychosocial importance of the thelarche for gynaecology was the subject of an investigation in 533 women. Psychometrically personality traits (FPI) and intelligence level (MWT) were examined. Thelarche started the earlier the younger the women examined (p less than 0.001). Women with higher school leaving age and above-average intelligence went through thelarche earlier than those with lower school leaving age (p less than 0.01) and below-average intelligence (p less than 0.01). Breast development in the phase of puberty was observed with greater attention by younger women with higher level of education than by older women with lower level of education (roughly estimated by school leaving age and intelligence level). Thelarche was observed with greater attention by sociable, vivacious, extrovert women than by unsociable, introvert women (p less than 0.001). Women who consciously observed their breast development reported very regular cycles more often than expected (p less than 0.05) and mostly were of ideal weight (p less than 0.001). The practical importance of the thelarche experience for gynaecology manifests itself above all in the breast prophylaxis behaviour. The more attentively the women observed their breast development the more importance they attached to prophylactic medical breast examinations (p less than 0.01) and the more frequently they examined themselves (p less than 0.01) which worried them more rarely (p less than 0.05). The effect of the thelarche experience on future breast prophylaxis behaviour underlines the importance of early health education for preventive gynaecology.


[Treatment of vulvar cancer (author's transl)]. This is a report on 120 cases of vulvar cancer. The mean age at diagnosis was 66.5 years. 25% were younger than 60, and 10% younger than 50 years. 95% were squamous cell carcinoma. The main site of the primary lesion were the labia (71%). 55 patients had palpable nodes in the groins. 12% of all women (=28% of those treated by radical vulvectomyl) had metastases in the groins. 54 (45%) were treated by radical vulvectomy, of which 23 (43%) received postsurgical radiation. 63 patients had minor operation with consecutive radiation in 51 (81%) of them. The overall 5 year survival rate was 43%. It was 65% in the group treated by radical surgery and 24% in the group of minor surgery and radiation. The radical vulvectomy with bilateral inguinal and femoral lymphonodectomy is recommended as treatment of choice in all suitable cases. The radiation cannot replace radical surgery.


Influence of fetal sex on the concentration of amniotic fluid testosterone: antenatal sex determination? Amniotic fluid testosterone was measured by radioimmunoassay in 226 samples taken between the 12th week of pregnancy and birth. The effect of fetal sex on the level of this androgen was determined and the usefulness of the parameter for predicting fetal sex assessed. Testosterone was measured using an antibody raised in rabbits against testosterone-3-carboxymethyloxime-BSA. The antiserum cross-reacted strongly with 5alpha-dihydrotestosterone so that the values reported were refered to as measuring "immunoreactive testosterone" levels. Male fetal values were highest between the 12th and 15th week of pregnancy reaching a maximum mean of 501 +/- 185 pg/ml gradually falling during the remainder of pregnancy to 281 +/- 74 pg/ml, the difference in values between the first half and the end of pregnancy being highly significant (p less than 0.0005). Female fetal values did not vary significantly during the course of gestation, the minimum mean value being 179 +/- 50 and maximum 253 +/- 98 pg/ml. The fetal amniotic fluid sex difference was highly significant during the first half of pregnancy (p less than 0.0005) and at 12-15 weeks a successful prediction of fetal sex was possible, using testosterone, in 39 out of 41 cases. At birth on the other hand there was no difference between male and female fetal fluid levels. The method can also be used to detect disturbances of intrauterine sexual development as exemplified by the case of a Klinefelter syndrome where female testosterone values were found at the time of sexual differentiation. Thus the measurement of unconjugated testosterone in amniotic fluid would seem to offer not only an addition to chromosomal analysis for prediction of fetal gender but also be a valuable tool for detection of disturbances of intrauterine sexual development i.e. when genetic sex and sex-specific hormone production are discrepant.


Studies on the haemodynamic action of complamin in pregnancy. In the present work, an attempt has been made to verify whether Complamin improves placental circulation as suggested by several authors. Complamin was administered intravenously to patients in the last trimester of pregnancy and its action on blood pool dynamics was examined over 30 min. The results from 30 investigations showed that a significant reduction in uteroplacental blood pool occurred. The production of placental hypovolaemia, which led to a reduction in blood pool of more than 30% in some cases, is regarded as a potential danger to the fetus.


[Changes in carbohydrate tolerance in the puerperium by inhibition of lactation with bromocriptine and quinestrol (author's transl)]. In the present study the influence of bromocriptine on carbohydrate tolerance was examined and its effects compared with those of an estrogenic compound (Quinestrol). Sixteen patients were studied in each group. The controls consisted of 16 women who breastfed their children. No significant difference was found in the oGTT in patients who had Quinestrol compared with the controls. However blood sugar values in women receiving bromocriptine were significantly lowered when compared with values of individuals who had Quinestrol. The reduction of blood sugar values depends on the dosage of bromocriptine. Inhibition of lactation with bromocriptine may lead to false negative results in patients who are at risk to have a prediabetic condition.


[Menarche--psychosomatic and psychosocial aspects for the gynaecology (author's transl)]. Does menarche represent such an important event for girls during puberty that it affects the experience of later gynaecological events in women? This was examined quantitatively in 5 series of investigations in 300-500 women. The data were collected by questionnaires and psychometric test methods. Can menarche provide more information to the psychosomatically interested gynaecologist than was previously thought? Early menarche occurred more frequently than expected, not only in younger women examined but also in those with higher school leaving age, higher intelligence and without neurotic personality traits. Women with later menarche attached less importance to sex, were more afraid of labour pains and thought less of labour preparation courses. Late menarche also showed a relation to the menopause insofar as impairment of the feeling of full usefulness and negative effects on sex were feared more frequently than expected. The menarche experience as a rather painful and/or surprising event showed relations to sociologic-pathological data and later gynaecological events. Women with painful menarche experience mostly belonged to the older generation, had a lower education level and rather unstable personality traits. The more painful the experience of menarche, the more frequent were later irregular cycles and menstruation was experienced as very painful. Negative consequences after gynaecological operations were found more frequently than expected. This was shown quantitatively by the example of uterus removal and mastectomy. With painful menarche experience impaired well-being during pregnancy and very painful confinements were reported more often than expected. In women who remembered the menarche as a rather surprising event we found more frequently lower school education, late menarche and no or inadequate sex instruction. The more surprising the experience of menarche was, the more frequent were unstable personality traits and psychosomatic disorders. Women to whom the menarche was not a surprise reported fewer side effects of ovulation inhibitors, experienced less troublesome confinements and were less afraid of uterus removal and the menopause. Where the menarche was very painful as well as a very surprising event the relations to psychologic-sociological data and gynaecological complaints were particularly obvious. Knowledge of the menarche experience thus allows certain predictions as to how future gynaecological events and sex will be experienced and dealt with. This applies especially to the prediction and clarification of so-called psychosomatic complaints in gynaecology.


Incidence and importance of splenic sarcoid-like granulomas. In an attempt to further define the nature, occurrence, and relative incidence of splenic sarcoid-like granulomas, 412 splenectomy specimens were studied. In addition to their occurrence in sarcoidosis, granulomas were found in patients with Hodgkin's disease, chronic uremia, non-Hodgkin's lymphoma, and selective IgA deficiency. The inability to demonstrate a specific responsible organism suggests that the lesion is not of infectious cause. The location of the lesions in the areas of antigen-trapping in the spleen, and their occurrence in both neoplastic and nonneoplastic diseases associated with abnormal or defective immunity suggests that they represent morphologic evidence of a nonspecific defect in antigen processing.