Mapping the putative RNA helicase genes by sequence overlapping. An 'electronic' gene mapping procedure based on computer-aided search for overlapping gene sequences was used to identify adjacent genes and localize several putative RNA helicase genes to different chromosomes. PRP28 and AMD1 genes map to the right arm of chromosome IV next to sup2, which encodes a tyrosine tRNA. PRP16, previously mapped to chromosome XI, is tightly linked to MRP-L20. PRP22 is adjacent to PRE1, whose chromosomal location is currently unknown. The utility of this approach in yeast gene mapping is evaluated.


Structure and expression of the ABF1-regulated ribosomal protein S33 gene in Kluyveromyces. The abundant multifunctional protein ABF1 of Saccharomyces cerevisiae binds to the upstream region of several genes, including some ribosomal protein genes like the one encoding protein S33. Deletion of the ABF1-binding sequence lowers the transcription of these genes three- to more than ten-fold. We have isolated the S33 genes of two related yeast species, Kluyveromyces lactis and Kluyveromyces marxianus. Comparison of the nucleotide sequences of these S33 genes with their counterpart from S. cerevisiae shows a strong sequence similarity covering the whole of the coding regions. In contrast, little or no sequence similarity is found in the 5'-flanking regions of the three genes. Also the trailer regions differ considerably in both length and sequence from one species to another. An ABF1-binding site is present in the upstream region of the S33 gene of K. marxianus. Retardation analyses showed that this sequence is able to bind a protein present in Kluyveromyces cells with a molecular mass somewhat lower than that of S. cerevisiae ABF1. Functional analyses, using a beta-glucuronidase reporter system, showed that the ABF1-binding site is indeed involved in transcription activation of the K. marxianus S33 gene in Kluyveromyces cells. A S. cerevisiae ABF1-gene-specific probe showed only weak hybridization with Kluyveromyces DNA and Northern blots did not show a signal. These results indicate that S. cerevisiae and Kluyveromyces contain functionally related but structurally dissimilar ABF1-type proteins.


The sequence of a 12 kb fragment on the left arm of yeast chromosome XI reveals five new open reading frames, including a zinc finger protein and a homolog of the UDP-glucose pyrophosphorylase from potato. We report the sequence of a 12,399 bp DNA fragment from the left arm of Saccharomyces cerevisiae chromosome XI. This fragment is located between the genetic loci mif2 and mak11. We have detected five new open reading frames (ORFs) longer than 300 bp provisionally called YKL248 to YKL252. One of them, YKL248 encodes a homolog of the UDP-glucose pyrophosphorylase from potato. The product of YKL251 contains the consensus for zinc binding proteins, similar to those of a number of fungal transcriptional activators. The three other ORFs do not show significant homology to known protein.


[Balint groups in psychotherapy of elderly patients]. Care of the elderly is typified by the relationship: elderly client/patient--younger helper/therapist. In Balint groups, relationships in interpersonal interactions are examined. This leads to a "patient-oriente" view and enables the participants to formulate a "comprehensive diagnosis". Multi-professional "gerontological"-Balint groups reduce reciprocal prejudices and value-judgements and promote cooperation between professional groups, further the understanding of the elderly in need of care, as well as the formulation of a patient-oriented "comprehensive treatment plan". By including creative productions in the Balint-group process, unconscious determinants of disturbed interpersonal relationships can be made "visible".


The sequence of a 9.3 kb segment located on the left arm of the yeast chromosome XI reveals five open reading frames including the CCE1 gene and putative products related to MYO2 and to the ribosomal protein L10. We report here the sequence of a 9.3 kb DNA segment of chromosome XI of Saccharomyces cerevisiae, located between the MAK11 locus and the centromere. This sequence contains four long open reading frames (ORFs), YKL160, YKL162, YKL164, YKL165 and part of another ORF, YKL166, covering altogether 90% of the entire sequence. One of these ORFs, YKL164, corresponds to CCE1. Translation products of two other ORFs, YKL160 and YKL165, exhibit homology with previously known S. cerevisiae proteins: the ribosomal protein L10, and the MYO2 gene product, respectively.


[Report on professional workshops "Aging and psychotherapy"]. Since 1989, annual scientific meetings "Age and psychotherapy" have been held in Erlangen, and since 1991, in Bonn. For each meeting a special topic has been selected such as, "Multimorbidity and Psychotherapeutic Implications," "Dementia and Psychotherapy," "Sexuality and Partnership." In addition to scientific papers related to the topic, courses, seminars and workshops have been offered since 1992 to exchange practical knowledge about psychotherapy with the elderly (e.g., autogenic training, family work, Balint-group, family therapy, art therapy, psychotherapy in psychogeriatrics, self-experience workshop, assertiveness-training, supervision). In addition to advanced training and continuous education, the main objective of these meetings has been to offer a forum to share knowledge and experience with professionals working in psychotherapy with the elderly.


[Aging--a growing challenge for us all]. The problem of an ever increasing overaging of the population presents a challenge to both science and politics. The author has chosen three particular aspects of this problem: (1) Aging and being old--a biological reality, (2) aging and growing old--a social burden and challenge to society, (3) reflections on old age and therapeutic programs. The study finishes with a "praise of old age".


[Aging--from the molecule to the organism]. Age-related changes at the molecular, cellular and organ level, as well as at the organism level are heterogeneous with respect to their timing and intensity. Theories on aging are numerous, but for none is there yet any strong, convincing evidence, particularly in regard to whether or not age-changes are programmed or are due to accumulations of random changes in constituent cells. Recent studies indicate, however, that DNA damage and repair may be central to cellular senescence, e.g., there is a direct relationship between the repair capacity and the maximum life span of a given species. The limited division potential of normal human diploid fibroblast cells in vitro is well documented and has been established as a model for cellular aging. Thus, fibroblasts taken from young individuals have a greater total doubling capacity as compared to fibroblasts derived from older individuals. Aging of the brain, heart, liver, and locomotory system are discussed. Within the context of organism aging the multimorbidity, chronic diseases, as well as some peculiarities of pharmacokinetics are also discussed.


[Aging of the immune system and sequelae for rheumatic diseases]. Immunoreactivity is impaired in old individuals. This is due especially to a loss of signals as well as to a loss of corresponding receptors. Moreover, the regulation of the immune response is reduced. This causes an increase of infectious diseases and of autoimmunopathies. With regard to rheumatic diseases there is a significant decline of reactive states in contrast to the manifestation of autoimmune arthritis. However, this is modified by nonimmunological factors such as hormones, which explains the predominance of females.


[Chlamydia infection and salpingitis].

[Chlamydia infection and salpingitis]. Chlamydia trachomatis is the most prevalent etiologic agent in women with uncomplicated salpingitis. This presentation reviews the current aspects of etiology, diagnosis, therapy, prevention and complications of this disease. The other clinical manifestations of chlamydial infection are also discussed.


[Determining progesterone in saliva].

[Determining progesterone in saliva]. A radioimmunoassay for the determination of progesterone in saliva using a 125J-labelled progesterone derivate has been developed. The assay is characterized by the excellent sensitivity of 3.12 pg progesterone/ml. During the menstrual cycle of normal women the biphasic rhythm of progesterone in saliva could not been clearly demonstrated. In the follicle phase high peaks of progesterone have been shown and even in the luteal phase individual low values have been observed. The circadian rhythms of progesterone in saliva are characterized by irregular oscillations. The saliva flow rate is not responsible for the progesterone concentration. The measurement of progesterone in serum seems to be more useful in the diagnosis of sterility.


[Rheumatic diseases in advanced age--psychological aspects]. This paper discusses the importance of cognitive representation and individual patterns of behavior for coping with chronic disease. Chronically ill patients differ very much in their psychic situation. Biographical and situational factors and the future perspective contribute to these interindividual differences. Diagnostic and therapeutical tools are discussed from a psychological perspective.


[Characteristics of pharmacotherapy of rheumatic diseases in advanced age]. Drug treatment in the polymorbid elderly should focus on the more important symptoms. Pharmacokinetic differences should be considered, e.g. a reduced volume of distribution and decreased liver and renal function. Special alterations in the pharmacodynamics with respect to the central nervous system and other organs are important. Drug therapy in the elderly has to be done very cautiously. The indication, dosage and duration of therapy has to be evaluated again and again. Antirheumatics in the elderly should improve the quality of life avoiding untowanted side effects, especially of the gastrointestinal tract, the renal function and bone marrow. Non-narcotic analgesics and opioids may be helpful, when antirheumatics were not tolerated.


[Value of the metoclopramide test in diagnosis of hormonal causes of female sterility]. A retrospective study was used to assess the diagnostic value of the metoclopramide (MCP)-stimulation test for diagnosing hormonal infertility in women. 1326 couples sought help at the hormone-counselling laboratories at the University Gynaecological Hospital in Heidelberg during a six year period and were evaluated with a standardized diagnostic program. The patients were grouped as manifestly hyperprolactinaemic, normoprolactinaemic or functionally hyperprolactinaemic, according to their basal serum prolactin (Pr)-level, and the results of the MCP-stimulation test. The number of patients in the normoprolactinaemic group varied from 894 to 1188 and functionally hyperprolactinaemic varied from 263 to 19 patients, depending on the cut-off value selected. We used cut-off values of 200, 250, 300 or 400 ng/ml in evaluating the MCP response. During a two year follow-up, 40% of the women conceived. Increasing Pr-levels, at stimulation, were associated with significantly more spontaneous pregnancies. Thus more women conceived in the functional hyperprolactinaemic group than in the normoprolactinaemic group. 281 women had used a dopamine agonist (21%). Women in the bromocriptine group (except manifestly hyperprolactinaemic patients) had significantly higher pregnancy rates than those not treated with bromocriptine. This results was particularly significant for women with normoprolactinaemic. It was caused by higher bromocriptine induced conception rate. 60% of the therapeutic pregnancies occurred in normoprolactinaemic women receiving the dopamine agonist therapy. Our results suggest that MCP-stimulation induced functional hyperprolactinaemia is not required for a successful approach. In sterility of unknown origin with normal basal Pr serum levels, a three month trial with low-dose dopamine agonist can be tried.


Arthritis in the elderly.

Arthritis in the elderly. Rheumatic diseases affect individuals of all ages. Both incidence and prevalence vary between age groups, and the diagnosis and management of the same rheumatic disease may be very different at the various ages. It is thus important to recognize the spectrum of rheumatic disorders in age-specific groups. The functional decline of cells, tissues and organs does not occur at the same rate in all individuals. This results in an increased variation with aging. It has important clinical consequences in the diagnosis of disease in the elderly with risk of both underdiagnosis and overdiagnosis. The increasing number of elderly, the high prevalence and the specific diagnostic and therapeutic problems of rheumatic disorders in the elderly call for some rheumatologists to focus an interest in geriatric rheumatology.


[Results of therapy of anemia in pregnancy]. Among 106 pregnant women with anaemia a typical state of iron deficiency could be shown at only 36.8%. 22.5% of the patients had a decreased vitamin B12 level without any characteristic symptoms of a megaloblastic anaemia. Predominantly the grade of the anaemia was small. The mean value of hemoglobin lied at 7.1 +/- 0.59 mmol/l. The severity of the anaemia didn't show any connection to the vitamin B12 level or parameters of the iron metabolism. With a combined therapy of iron, folic acid and vitamin B12 an increase of the Hb-level could be noticed at only 44.3% of the patients. The haematological findings, taken before the therapy, as well as the therapy results show that an important part of anaemias in pregnancy is caused by a complex genesis as a result of immunological reactions in pregnancy.


[Use of tramadol versus pethidine versus denaverine suppositories in labor--a contribution to noninvasive therapy of labor pain]. Because tramadol does not exhibit an depressive effect on ventilatory activity it is often be used in the obstetrical analgesia, at most in form of an intramuscularly injection. In a prospective study on at all 49 women under labour the clinical effect of the noninvasive rectal application of Tramadol, Pethidin, and Denaverin has been compared. The first dosage was 100 mg of all substances. Around the half of the women said that analgetic effect was good or very good. On only every fifth it was sufficient or not enough. The effect was at near the same in all treatment groups. Because of a low incidence of maternal side effects, the absence of side effects on the newborn, and near the same results on the analgetic effect of parenteral application in other studies, tramadol suppositories can be recommended for obstetrical analgesia.


[Sports in advanced age in inflammatory rheumatic diseases]. The positive effect of moderate physical activity on cardiovascular system, psychological condition, immune reactions and joint biology are wellknown. They seem to facilitate pain control and to stimulate the metabolism of skeletal tissue and joints also in elder patients with rheumatoid arthritis if certain prerequisites are considered. The possible influence of physical activity on the natural course of the disease has not yet been investigated. The recommended type and extent of sports activity therefore have to be carefully selected with regard to the pathogenesis of the disease and their inflammatory changes as well as the patients individual medical conditions.


[Value and characteristics of physical medicine and health resort medicine in advanced age]. Physical medicine and spa medicine both have the impetus of rehabilitation in common. In addition, they share the therapeutical orientation toward the performance capacity of organs and functional systems, as well as to activities of daily living, the consideration of chronobiological rules of training and adaptation, and an acknowledging of the fact that diseases and, therefore, the basics of rehabilitation are constantly changing. With increasing age the relation of therapy to function resp. rehabilitation becomes increasingly important. Gerontorehabilitation is distinguished from general rehabilitation by the following three characteristics: a) the focus on particular diseases of the elderly, for instance osteoporosis; b) the therapeutical awareness of multimorbidity with the obvious involution of the skeletal muscle mass, the labilization and generalization of vegetative reactions and the special psychosocial situation; c) the consideration of specific reactions of the organism in advanced age to additional and unexpected events (immobilization syndrome, regulative rigidity, long-term adaptation). Gerontorehabilitation has to deal with specific problems of the elderly, problems that may seem medically banal, but which may be partly either serious or at least very inconvenient, e.g., the multifactorial-caused kyphosis, motor deficiency and slowed reactions, the tendency to fall, itching or stinging extremities due to many causes, latent heart insufficiency of undetermined origin, disturbance of sleep and therefore of recreation, and impairment of higher brain functions.


[Irritation of the anterior nerves of the abdominal wall--Ibrahim syndrome]. The irritation of the nerves of the anterior abdominal wall (nervi intercostals X-XII) may imitate salpingitis, appendicitis or intraabdominal adhesion. By gentle palpation of the wall of the lower abdomen, spec. in the region of the lateral part of the musculus rectus, the points of pain are to be localized. Xylocaine-injection may give a pain-relieve for a short period of time. Mostly, there must be an operation to loosen adhesions and to dilate the nerve-exits from the lateral part of the musculus rectus.


[Umbilical cord compression by an amnionic band]. A case report is given from personal observations of an intrauterine death due to constriction of the umbilical cord by amniotic band. Previously reported cases and current hypotheses for the etiology of amniotic band are reviewed and merit clinical attention.


[Mucocele of the appendix in highly differentiated adenocarcinoma]. A patient 69 years old had been admitted at the University Women's Hospital Berlin because of a suspected ovarian tumour. Outside a computed tomography was done. In the small pelvis a tumour partly cystic and partly solid at the right side could be confirmed sonographically. Because this an operation was indicated. After opening the abdomen the internal female genital organs were in conspicuous with the exception of extensive adhesions. Histologically we found a mucocele of the vermiform appendix with a highly differentiated adenocarcinoma. All tissue layers were infiltrated and perforated. This combination of findings is very seldom, because carcinomas of the appendix could be proved only in 0.01 per cent of all appendectomies.


[The characteristics of the ultrastructural changes in yeast-like fungi of the genus Candida exposed to therapeutic-range ultrasound and nystatin]. The electron microscopic study of the ultrastructure of yeast-like fungi of the genus Candida under the action of nystatin and sonication, as well as the action of these two factors used in combination, was carried out. In this study the degree of preservation of the structure of fungal cells was evaluated and the percentage of cells with different ultrastructural changes was determined. Observations made 3 and 24 hours after sonication and treatment with nystatin, used in combination, showed that ultrastructural changes in fungal cells were more pronounced than in the cells subjected to the action of nystatin alone. 24 hours after the combined physico-medicinal treatment of Candida the percentage of nonviable blastospores among them was 5-fold higher than that of such cells among Candida subjected to treatment with nystatin alone and more than 20-fold higher than among Candida subjected only to sonication. These data on the increased fungicidal effect of nystatin used in combination with sonication substantiate the expediency of the above-mentioned physico-medicinal treatment in cases of candidal lesions of the skin and its appendages, which is one of the ways for increasing the effectiveness of the treatment of this mycosis.


[Spontaneous variability in a population of Candida albicans strains]. The spontaneous variability of the populations of C. albicans strains of different genesis in the morphological properties of their colonies and in the potential of the activity of their extracellular proteolytic and phospholipid enzymes has been studied. The isolated types of colonies, differing in their morphology, have the phenotypic character of variability. Different populations of strains exhibited variability in the activity of enzymes, depending on morphological variants isolated from these populations. Selected morphological variants with high potential of their proteolytic enzymes retained stability in this property for 5 generations and can be used in medical practice for the isolation of C. albicans antigens.


[Associations of the soil amoeba Hartmannella rhysodes with the bacterial causative agents of plague and pseudotuberculosis in an experiment]. Some aspects of relationships between soil ameba and the causative agents of plague and pseudotuberculosis, capable of forming natural associations, are considered. Ameba can phagocytose bacteria causing plague and pseudotuberculosis. Cases of the preservation of individual bacterial cells at the stationary phase and in precysts of amebae have been registered.


[The vital activities of enterobacteria in an aqueous medium in the absence of sources of organic nutrition]. Heterotrophic bacteria were found to be capable of proliferation in physiological saline and distilled water. In 1988-1989 experimental studies were made with a view to establish the role of the gaseous phase of atmospheric air and the products of the autolysis of dead bacteria as the sources of organic nutrition. The studies revealed that the complete removal of atmospheric air from vials with bacterial suspension completely stopped the stimulation of reproduction. In vials with a higher concentration of dead bacterial bodies the proliferation rate was 2- to 400-fold (on the average, 118-fold) higher. The products of the autolysis of bacterial bodies proved to be of no importance as an independent source of organic nutrition for heterotrophic bacteria. The mechanism of the assimilation of autolysis products is "switched on" by biologically active geomagnetic disturbances. The mechanisms of the increase of bacterial biomass remain unclear.


[The hydrophobicity of gram-negative bacteria isolated from patients with inflammatory and suppurative-destructive lung diseases]. Hydrophobic properties of 11 enterobacterial strains and 12 Pseudomonas aeruginosa strains isolated from patient with inflammatory and purulent destructive diseases of the lungs were studied. The hydrophobic properties of the isolated bacteria were determined by the method of salting out with ammonium sulfate. A high correlation (r = 0.56) between the above-mentioned properties of gram-negative bacteria and their isolation rate from patients with destructive diseases was established. The hydrophobic properties of bacteria were supposed to be of importance in the process of the colonization of pulmonary tissues with bacterial flora.


[The virulence of Streptococcus pneumoniae strains--the causative agents of pneumococcal infection at different sites]. A total of 256 S. pneumoniae strains, the causative agents of infectious processes with different localization, were studied for their virulence (in experiments on mice), neuraminidase and aldolase-protease activity (APA). In pneumococcal strains isolated 18-20 hours after intraperitoneal infection their virulence for mice increased, on the average, 1,000-fold and the average level of extracellular and cellular neuraminidase and APA increased 2- to 5-fold in comparison with the initial values. Pneumococcal strains causing acute pneumococcal infections with different localization, or the aggravation of such infections, exhibited higher virulence for mice and higher levels of neuraminidase and APA, while the inflammatory process at the period of clinical remissions was mainly maintained by S. pneumoniae cultures with low virulence.


[The identification of nondiphtheritic bacteria of the genus Corynebacterium and the determination of their antibiotic sensitivity]. A total of 221 patients with nonspecific inflammatory processes were studied with a view to determine the occurrence and species composition of microorganisms of the genus Corynebacterium on the mucous membrane and in the secretions of their genitals. Different representatives of this genus were detected in 23.1 +/- 3.5% of patients with cervicitis and endometritis and in 48.7 +/- 5.7% of patients with prostatitis. Among the isolated bacteria of this genus C. pseudogenitalium, C. genitalium and C. xerosis, as well as Corynebacterium cells of group JK, occurred most frequently. The strains under study were found to have high antibiotic resistance. On the basis of their cultural features, growth rate, the degree of contamination of the genitals and sensitivity to antibiotics, bacteria of this genus were differentiated into macro- and microcoryneforms.


[The rapid diagnosis of acute streptococcal infection in children]. The present work deals with trials of the method of rapid diagnosis of streptococcal infection, carried out in children's infectious hospital, with the use of a new diagnostic kit. The proposed diagnosticum has proved to be highly sensitive and specific in scarlet fever and tonsillitis. The sensitivity and specificity of the diagnosticum depend on the duration of the disease, prehospital treatment and the quality of the bacteriological analysis.


[An outbreak of cholera (El Tor) in Samarkand Province, Uzbekistan in 1990]. A group outbreak of cholera caused by Vibrio eltor in the Samarkand Province++ in 1990 is analyzed. The retrospective analysis of the isolation of V. cholerae from water of surface reservoirs has been made. The study points out that since the cholera epidemic of 1985 V. cholerae avirulent strains, serogroup O1, have been periodically isolated in the Samarkand Province. The conclusion has been made that the isolation of even avirulent strains only from environmental objects is indicative of the unfavorable epidemiological situation in this area and of the necessity to take measures for improving epidemiological surveillance.


[The use of a method for the electrophoretic typing by protein profiles of bacteria in the genus Acinetobacter for epidemiological diagnosis]. On the basis of data obtained by the biological characterization and electrophoretic typing of Acinetobacter sp. cultures by the spectra of membrane proteins epidemiological relationships, routes of transmission and specific features of the circulation of strains causing purulent inflammatory diseases have been determined.


[Multiyear observations of the dynamic epidemic process in Sonne dysentery in a small district of Vladimir Province]. On the basis of the epidemiological analysis of morbidity data for several years the many-sided dynamic characterization of the epidemic process of Sonne dysentery in a small district is presented. As revealed by this analysis, the epidemic process developed in the presence of residual activity of the water factor; this activity was mediated by transmission of this infection through milk products contaminated in the course of their manufacture and distribution. The possibility of appearance of an intricate chain of interrelated transmission factors is shown, as exemplified by a specific epidemic situation; to determine the activity of these factors, profound epidemiological analysis of morbidity data is needed.


[The phages of halophilic vibrios and their use]. The range of the lytic activity of 46 phages of parahemolytic vibrios isolated from lysogenic strains, sea water samples, crabs and mussels has been studied. The phages are represented by virions belonging to morphological groups II, IV, V according to the phage classification currently used in Russia and to different serological groups. No relationship between the sensitivity of vibrio strains to the phages under study and the specificity of serotypes O and K has been established. The preparation of diagnostic phage [see text] suitable for the identification of 82% of strains of parahemolytic vibrios has been proposed.


[Protection from virulent Salmonella groups B and D after the peroral immunization of chicks with a hybrid of Salmonella typhimurium and Salmonella dublin]. Chickens over 10 days old, infected orally with virulent salmonellae, were found to remain alive. Histologic investigation showed the development of mild enteritis and more pronounced, lasting for more than two weeks, inflammation of the cecum, dissemination and focal lesions in the liver (granulomas, necrosis). In experiments on the oral immunization of 3-day old chickens the bivalent hybrid of S. typhimurium vaccine strain 274 and S. dublin induced only pronounced blast transformation in lymphatic follicles of the cecum, hyperplasia of activated macrophages and formation of granulomas from these macrophages and lymphocytes. After oral challenge of the immunized chickens with virulent salmonellae of group B (S. typhimurium) and group D (S. enteritidis, S. gallinarum-pullorum) the chickens exhibited sharply pronounced protection against adhesion, colonization and invasion, and a few penetrating bacteria were rapidly destroyed by immune macrophages. Hybrid strain 274/O9 proved to be suitable for use as oral bivalent vaccine against salmonellosis in chickens.


[The safety of a new chemical typhoid preparation containing a complex of Vi and K antigens in tests of its acute and chronic toxicity]. Acute and chronic toxicity of a new chemical typhoid preparation containing the complex of surface Vi- and K-antigens has been studied. The study has revealed that the preparation, when introduced subcutaneously and intravenously in immunizing doses in a single injection or in multiple injections, produces no toxic effect on the organs and tissues of experimental animals. In experiments of chronic toxicity the microscopic study has shown pronounced hyperplasia of the lymphoid system with enhanced macrophage reaction in the spleen, thymus, mesenteric lymph nodes and Peyer's patches in the small intestine.


[An immunoenzyme test system for determining gaprin in the air]. A highly specific and sensitive enzyme immunoassay system for the quantitative determination of haprin in the air at a concentration of not less than 0.0001 mg of haprin per m3 of air has been developed. The assay system has been approved at the Svetloiarsk plant for the production of vitamin protein concentrate and can be used for the control and evaluation of haprin pollution of the environment at areas adjoining microbiological plants.


[The effect of the structural components of Staphylococcus aureus on the interaction of T- and B-lymphocytes]. The results of studies on the influence of staphylococcal peptidoglycan and cell walls on the cooperative interaction of T- and B-lymphocytes in the process of immune response to thymus-dependent antigen are presented. Peptidoglycan has been found to produce, depending on its dose, a suppressive and stimulating effect on the interaction of T- and B-cells. Cell walls exhibit only stimulating action under the same experimental conditions. The suppressive action of peptidoglycan is mediated by T-lymphocytes.


[The preventive activity of monoclonal antibodies specific to the lipopolysaccharide of Francisella tularensis]. The preventive activity of five monoclonal antibodies (McAb) in experimental tularemia was evaluated. McAb produced by hybridoma FB11-k (IgG2a), specific to F. tularensis lipopolysaccharide, prevented the death of mice and guinea pigs infected with F. tularensis virulent strain 503 of the holarctic subspecies.


[Changes in the phagocytic activity of macrophages under the action of different doses of antibiotics]. Penicillin, streptomycin and gentamicin, when introduced into mice in a single injection in doses of 0.5-500,000 U/kg, produced different changes in the phagocytic activity of mouse peritoneal macrophages. Bactericidal doses of these antibiotics either suppressed the activity of macrophages or left it unchanged. Their sub-bactericidal doses enhanced the phagocytic activity of macrophages. Combined use of penicillin and streptomycin produced a synergic effect.


[Neuraminidase activity in representatives of the genus Francisella]. In two Francisella species (F. tularensis and F. novicida) neuraminidase activity, heretofore unknown, was detected. The enzyme exhibited specificity with respect to the substrates used in the investigation, neutralizing natural mucins, but not other compounds (glycoproteins and glycoproteins). All F. tularensis strains were found to have enzymatic activity irrespective of their subspecies, but neuraminidase activity was higher in the strains belonging to the American subspecies. Experimentally obtained F. tularensis noncapsular variants possessed higher neuraminidase activity than the capsular parent strains. The conclusion on the possible role of this enzyme in F. tularensis colonization of the host body was made.


Long-term prognosis of ischemic stroke in young adults. Prognostic information is provided for 74 young adults (age 16-40 yrs, mean age at stroke 29.5 yrs), who suffered from ischemic stroke and survived the first month after the stroke. The patients were followed for 13-26 yrs; in total for 1190 yrs after their stroke. At follow-up 12 of the patients were dead, mostly from severe underlying disease that was complicated by ischemic stroke. In 3 cases death was unrelated to cerebrovascular disease. Among the surviving 62 patients, 7 had experienced recurrent ischemic events (3 reinfarctions, 4 TIA:s). These 7 patients all had risk factors for cerebrovascular complications already at the time of their primary stroke. It is concluded that the long-term prognosis for ischemic stroke in the young adult is favourable. The recovery from neurological deficits is usually good (exceptions are occlusions within the internal carotid and middle cerebral arteries), the risk for recurrence is low (1.1-1.2% annually), and the social prognosis with respect to working capacity and family relation is fair.


Leucocyte aggregation in acute cerebrovascular disease. We evaluated leucocyte aggregation in 26 patients with ischemic stroke and in 10 patients with transient ischemic attacks (TIA), previously untreated, within 24 h from the onset of symptoms. The evaluation was also performed in 30 healthy subjects matched for age and sex. Leucocyte aggregation was significantly higher in patients than in controls (p < 0.01 post hoc Tukey test). Within patients, those with stroke showed a significantly higher aggregation than those with TIA (p = 0.01 post hoc Tukey test). Moreover, stroke patients with the poorest outcome showed significantly higher values of leucocyte aggregation. These results indicate an involvement of leucocytes in cerebral ischemia and suggest that changes in their aggregability may play a role in the evolution of the disease.


The topography of microthrombi in ischemic brain infarct. Following cerebral ischemia a tendency to increased coagulation can be detected. Vascular occlusion may develop either as a result of local thrombus formation or from emboli caused by circulating platelet aggregates. We studied the localization of microthrombi and their effects on tissue in double-hemisphere sections. Fresh brain infarcts showed a large number of microthrombi limited to the ischemic region. In more advanced infarcts they were found mainly at the border of the necrosis and diffusely distributed over both hemispheres. Older, subsiding infarcts showed only isolated microthrombi limited to the area of the necrosis. This indicates that great importance must be attached to microthrombi in infarct progression.


Cognition in epilepsy: a multichannel event related potential (P300) study. Auditory event-related potentials (AERP) were elicited in 68 epileptic patients and 30 age-matched controls. Epileptic patients had significantly prolonged N2 and P300 (P3) latencies compared with controls. Seven patients were above the range of 3 standard deviations from the control mean values. Amongst epileptics, patients with temporal lobe epilepsy had significantly prolonged P3 latencies compared to patients with idiopathic generalized epilepsy. Patients with abnormal EEGs had significantly prolonged P3 latencies compared to those with normal EEGs. Patients on anticonvulsant monotherapy had shorter P3 latencies, compared to patients taking a combination of two or more anticonvulsants. Patients on shorter duration of treatment had less prolonged P3 latencies compared to those on longer anticonvulsant treatment.


Reduction of antiepileptic drug dosage for monitoring epileptic seizures. Eleven epileptic patients, candidates for surgical treatment, were examined in order to localize epileptic foci. The daily doses of antiepileptic drugs (AEDs) were reduced by fifty per cent or less, and the reduced dosages were maintained until a seizure had occurred. The reduction resulted in seizures within five days among all patients, and the number of seizures increased significantly in comparison with the five-day period before AED reduction. The seizures so provoked were typical for each patient, as confirmed by clinical observation and video-EEG telemetry. No status epilepticus or withdrawal psychosis occurred. The AED concentrations at the time of the seizures were generally within the reference values.


CSF and serum ganglioside antibody patterns in MS. The authors determined CSF and serum IgG and IgM antibodies to seven gangliosides in 48 patients with multiple sclerosis. Differing ganglioside antibody patterns in CSF but not serum allowed to reclassify 93% of MS patients correctly when compared to patients with Guillain-Barré syndrome or neuroborreliosis. This suggest that the antibody patterns are neither random nor alike in inflammatory diseases of the nervous system. CSF ganglioside antibody titres were found to be different for patients with relapsing remitting (RRMS; n = 35) and chronic progressive (CPMS; n = 13) multiple sclerosis. Our study reveals characteristic ganglioside antibody patterns in MS and confirms previous evidence of disturbed immunoregulation in MS.


Patients with homocystinuria: high metal concentrations in hair, blood and urine. Patients with homocystinuria excrete a large amount of metal in their urine. Homocysteine similar to penicillamine, administration to methylmercury treated rats resulted in a large amount of urinary methylmercury excretion. These results suggested that the total metal amounts in the whole body of patients with homocystinuria might be decreased. However, actually metal concentrations in hair and plasma of these patients were higher than those of normal controls. High plasma and hair metal levels are not accounted for in patients with homocystinuria. The physiological metal excretory mechanism in which small amounts of metals bind to the small, plasma molecular substances filter through the kidney and emerge in the urine is necessary for reconfirmation. Strongly perturbed metal metabolism exists in the patients with homocystinuria.


Alcohol levels in cerebrospinal fluid and blood samples from patients under pathological conditions. We measured alcohol levels by the Cordebard method in 148 CSF samples from individuals who had abstained from alcohol for at least 7 days prior to the beginning of the study. Each blood sample was accompanied by a CSF sample from the same patient. CSF samples found to be normal after analysis were used as controls. Mean alcohol concentration in blood did not differ significantly between the control group and the groups with altered CSF. The group with altered CSF had statistically higher alcohol levels in CSF than in blood. CSF lactate, glucose and protein levels were not correlated with alcohol level. The results suggest the presence of endogenous alcohol in the CSF, with levels increasing in the presence of pathological processes involving the nervous system.


Mortality rate of Alzheimer's disease in Japan: secular trends, marital status, and geographical variations. The death rate from Alzheimer's disease (AD) in Japan was analyzed using death certificates for the years 1979 through 1990. The AD death rate has increased gradually year by year for both sexes. The overall death rates per 100,000 population of 35 years and over were 0.127 for men and 0.144 for women. Age-specific AD death rate increased exponentially up to the 65-69 age group and decreased thereafter. There were remarkable differences in the AD death rates among the four marital categories, among different prefectures and among the six occupational categories. Overall mean age at death was 63.5 years for men and 65.3 years for women.


Non-invasive dynamic assessment of the elasticity of intracranial structures. The dynamics of the speed of transcranial propagation of ultrasonic impulses has been established in humans. The possibility of detecting the changes in mechanical state of intracranial structures by dynamic measurement of the time of transcranial propagation of ultrasonic impulses (TUPT) has been ascertained for 10 healthy persons and 11 patients with different neurological pathology. The cerebrospinal fluid pressure (CSFP) was simultaneously monitored for 4 of the patients. Spontaneous fluctuations in TUPT and the changes caused by jugular veins, inferior vena cava compression, hyperventilation and temporary retention of breathing were detected for all investigated subjects. Spontaneous TUPT changes in the range of 0.25-0.85 x 10(-4) of initial mean value, which are related with cardiac and respiratory cycles, have been found in healthy persons while in patients they ranged from 0.07 x 10(-4) to 4.5 x 10(-4) of mean time. In healthy persons bilateral jugular vein compression leads to a decrease in TUPT by 1.8-3.0 x 10(-4), while the compression of inferior vena cava gives an increase in TUPT by 1.6-2.6 x 10(-4). Changes in TUPT during these maneuvers in neurological patients were found to be of different amplitude and direction. The rise of CSFP by 8.4-20.2 mmHg (mean 12.4 mmHg) was observed in 4 investigated patients during the compression of jugular veins or during the inferior vena cava compression, while the changes in TUPT obtained during each of such maneuvers were of opposite character. The results suggest that dynamic evaluation of acoustic impedance of intracranial system reflects the changes in the mechanical state of brain parenchyma.


HLA profiles of multiple sclerosis in Hokkaido, the northernmost island of Japan. We studied HLA haplotypes in 43 consecutive clinically definite MS patients in Hokkaido. The patients were classified into Group A, 12 patients with acute transverse myelopathy (ATM) during the course of illness, and Group B, 31 without ATM. We found an association with HLA-DQw7 in Group A, and with DR4 and DRw8 in Group B. The frequency of DQw7 and DR4 were significantly different between Groups A and B. This study may indicate the different genetic backgrounds between the groups. DRw8 and DRw52 antigens were significantly more common in MS than in controls. Our result is inconsistent with previous Japanese studies, and ethnic variation might be considered as a possible cause of the contradiction.


Encephalopathy in ifosfamide-treated patients. Acute encephalopathy following treatment with ifosfamide and mesna was observed in 5 (4 women and 1 men) of 28 patients (17.8%), with advanced sarcoma, lymphoma or ovarian carcinoma. This appeared within 2 to 7 days following the first dose of ifosfamide treatment, and included mental status changes, urinary incontinence, weakness, seizure activity, altered consciousness and psychiatric manifestations. Three cases were fatal, while two patients recovered completely. Brain CT and morphometric studies were normal in all the patients. Associated findings were myelosuppression, renal failure and electrolyte alterations.


Intracutaneous sterile water injections do not relieve pain in cervicogenic headache. Intracutaneous sterile water injections have been reported to relieve acute labor pain and cervical pain in whip-lash patients. A double blind cross-over trial has presently been conducted in 10 women with cervicogenic headache in order to investigate whether sterile water injections were effective in this disorder. No benefit was observed for either treatment (isotonic saline or sterile water), neither on pain during the first 14 days nor on neck mobility. We conclude that intracutaneous sterile water injections is not effective in cervicogenic headache.


Transient opsoclonus in organophosphate poisoning. Opsoclonus transiently occurred in the acute stage of combined parathion and methyl-parathion poisoning. Despite persistent cholinesterase inhibition this symptom subsided spontaneously. This observation provides strong evidence for cholinergic pathways being reversibly involved in isolated opsoclonus.


Visual half-field testing of memory functions in patients considered for surgical treatment of intractable complex partial epilepsy. The present research employed the visual half-field (VHF) technique to assess memory functions in normal subjects and in patients with unilateral temporal lobe epilepsy prior to surgery. Two studies were conducted. In Study 1, concrete and abstract words were presented to the left (LVF) or the right visual half field (RVF), and measures were made of response latencies, naming, free recall, and recognition. In Study 2, pictures depicting random shapes with low verbal association values were presented, and measures were made of latencies for identification and recognition of the shapes. Overall, the results showed a RVF advantage for words, but no lateralization for shapes. A selective hemisphere memory deficit was obtained for abstract words in patients with left temporal lobe lesions. Otherwise, no obvious lesion-related differences were found in the preoperative analyses. It is concluded that VHF testing of verbal information, but not abstract visuo-spatial information, is discriminative in assessing hemispheric functions in normal subjects and patients with temporal-lobe epileptic lesions.


Intrauterine growth in the offspring of epileptic mothers. The present paper concerns the fetal growth of 315 newborns of epileptic mothers prospectively followed from the beginning of pregnancy. In comparison with Italian standards, neonatal weight, length and head circumference at birth were below the 10th percentile in respectively 15.7%, 1.1% and 19.2% of the newborns. Weight at birth was above the 90th percentile in 8 cases. Observed frequencies were significantly higher than expected frequencies for both weight and head circumference. The percentage of newborns with a small head circumference increased significantly according to the number of drugs taken by the mother during the first three months of pregnancy: 7.1% with no drug, 16.8% with one drug, 23.6% with two drugs and 50% with three drugs. A statistically significant correlation was found between gestational age-adjusted head circumference and drug-level scores during the first trimester. Head circumferences below the 10th percentile were fewer among newborns treated with CBZ than among newborns treated with either PB or VPA.


Interictal brain 99Tc-HM-PAO SPECT hypoperfusion in patients with unstable partial epilepsy and normal CT. Brain perfusion was studied interictally with 99mTc-HM-PAO SPECT in 47 adult patients with partial epilepsy and normal brain CT. Epilepsy was classified as secondarily generalized in 24 patients, as complex partial in 17 patients and as simple partial in 6 patients. In 24 patients good seizure control was not achieved as these patients had a median number of 78 seizures during the preceding month, while in the rest of the patients seizure control was relatively good (less than 6 seizures during preceding month). Local brain hypoperfusion was observed in 41 or 87% of the patients. Hypoperfusion was located close to the EEG foci in 76% and equally often with temporal and frontal foci. Hypoperfusion and the EEG focus were located on the same side in 83%. Hypoperfusion was more frequent in secondarily generalized epilepsy and simple partial epilepsy than in complex partial epilepsy. Left-sided hypoperfusion was especially associated with complex partial epilepsy. It is likely that the significant epileptogenic brain area was revealed in patients with SPECT focus and EEG focus in the same brain area. In one of our patients MRI showed a small temporal lesion which on successful removal was identified as a low-grade oligodendroglioma. Abnormalities of regional brain uptake of HM-PAO demonstrated by SPECT in patients with partial epilepsy and normal brain CT give further information about pathophysiology in partial epilepsy; this may be of use both for selecting appropriate therapy and in presurgical localization of foci.


Spontaneous thoracolumbar spinal cord infarction: report of six cases. We present a retrospective study of 6 patients with spinal cord infarction in the territory of the Adamkiewicz artery. In all patients, the clinical picture was stereotyped: sudden onset of paraplegia and bilateral radicular pain, dissociated sensory loss below the level of infarction and sphincter dysfunction. Emergency neuroradiological investigation ruled out a compressive lesion in all cases. In one patient, spinal angiography was performed and identified an occlusion of the Adamkiewicz artery. Treatment was supportive and all patients had a substantial recovery over a period of weeks.


Sleep patterns in acute ischemic stroke. We studied polysomnographic recordings using an Oxford Medilog 9000 System in 18 patients with ischemic stroke in the middle cerebral artery territory. All patients underwent neurologic examination and brain CT scan within 5 h after the onset of symptoms. Polysomnographic recordings were started immediately thereafter and went on for three nights. Clinical and polysomnographic follow-up were performed 3 weeks after admission. The number and duration of REM phases were significantly reduced in the acute phase. This reduction correlated with the severity of neurological deficit at outcome and with the anatomical site of the lesion on CT scan. Our data provide evidence that polysomnographic recording is useful to detect symptoms of patients with different clinical outcomes during the acute phase of ischemic stroke.


Plasma lipids and lipoproteins in subtypes of stroke. We determined plasma lipid and lipoprotein concentrations in 131 patients (95 males, 36 females, mean age 71 years) 6 months after acute stroke onset. Compared to a reference population, the alterations of plasma lipid concentrations in stroke patients were moderate. However, the stroke patients had higher levels of triglyceride and lipoprotein (a) and lower concentrations of cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. Patients with different subtypes of stroke showed significant differences when compared with each other by analysis of covariance (with adjustment for age, sex, smoking, hypertension and diabetes). Patients with carotid or vertebral artery disease had the higher levels of cholesterol, triglyceride and apolipoprotein B, whereas high density lipoprotein triglyceride concentrations were higher in patients with cardioembolic infarcts.


Acute demyelinating disease. Classification and non-invasive diagnosis. Five young patients are described with biopsy-proven acute demyelinating disease. Two cases are classified as Schilder's disease, a particular childhood form of multiple sclerosis (MS) with atypical clinical manifestation, normal or atypical CSF-findings and large bilateral lesions in magnetic resonance imaging (MRI). Two further cases presented with a fulminant bout of MS with typical clinical picture and CSF-findings; they are classified as Marburg's disease. The last case was an acute second bout of classical MS. The biopsy seemed to be justified in 4 cases, but unnecessary in the last case. Localized proton magnetic resonance spectroscopy (MRS) performed in one case allowed us to examine the focal cerebral abnormalities directly and non-invasively. The spectra revealed a pattern typical of acute demyelination suggesting potential for a replacement of biopsy in the future.


Vascular pseudoparkinsonism.

Vascular pseudoparkinsonism. Vascular pseudoparkinsonism may be confused with idiopathic Parkinson's disease. Patients may be unnecessarily treated with anti-parkinsonian drugs while their underlying vascular disease is ignored. We investigated 250 parkinsonian patients seen in our Movement Disorders Clinic for a possible vascular etiology. After excluding those with a known secondary cause such as drug-induced parkinsonism, progressive supranuclear palsy, multiple system atrophy and hyperparathyroidism, brain computed tomography and/or magnetic resonance imaging were performed on those who showed poor or no response to levodopa. In those with an ischemic lesion demonstrated on neuroimaging, anti-parkinsonian drugs were stopped and the patients were reassessed. Eleven patients (4.4%) had ischemic brain lesions accounting for their parkinsonism. All were initially diagnosed as Parkinson's disease because of the prominence of bradykinesia and rigidity. Gait disturbance was also common, but resting tremor was distinctly absent. Three anatomical patterns with different prognosis were identified. Three patients with basal ganglia lacunar infarct recovered spontaneously, three with frontal lobe infarcts remained static and five with periventricular and deep subcortical white matter lesions had progressive deterioration. Autopsy in one patient confirmed bilateral frontal lobe watershed infarcts and the absence of brain stem Lewy bodies. Parkinsonian patients with poor or no response to levodopa therapy should be investigated for a vascular etiology.


Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease. Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.


Serum anti-GM1 and anti-GD1a antibodies in patients with motor neuron disease. Using an enzyme-linked immunosorbent assay (ELISA) sera from 100 individuals, 20 with motor neuron disease (MND), 25 with peripheral neuropathy (PN), 15 with degenerative dementia and 40 controls, were examined in order to detect serum IgM and IgG anti-GM1 and anti-GD1a antibodies. Patients with MND showed statistically significant higher levels of IgM anti-GM1 antibody compared to the control group. Three patients with peripheral neuropathy had very high levels of anti-GM1 and anti-GD1a antibodies. Antibody levels in patients with degenerative dementia showed no difference compared to the controls. These results suggest that a further inquiry into the role of serum anti-GM1 and anti-GD1a activity in motor neuron disease and peripheral neuropathy is necessary.


Alzheimer's disease: correlational analysis of three screening tests and three behavioral scales. We administered three cognitive tests (the Mini Mental State Examination, the Cognitive Capacity Screening Examination, and the Blessed Information-Memory-Concentration test) and three behavioral scales (the Blessed Dementia Scale, the Gottfries-Bråne-Steen scale, and the Sandoz Clinical Assessment Geriatric) to 41 patients with a clinical diagnosis of "probable" Alzheimer's disease (NINCDS-ADRDA criteria). The six measures demonstrated good reliability and high intercorrelation values. These findings provide further evidence for the strength of relationship between cognitive and behavioral measures in Alzheimer's disease.


Alertness and sleep in young men during military service. Alertness and sleep in healthy young men conscripted into military service were examined by testing personality characteristics and by completing questionnaires at the beginning of military service about their civilian life alertness and sleep, and by using polygraphic recordings during their military service. Sleep-time during service was restricted to 8 hours a night; 236 men answered the questionnaire on civilian life alertness and sleep; 116 men a Minnesota multiphasic personality inventory; 7 underwent conventional, and 29 static charge-sensitive bed sleep recordings. Daytime latencies to Stage 2 sleep were 11 +/- 2 min. Sleep latencies were the shortest 6 h after waking. Night sleep was normal in conventional recordings. Nocturnal activities in static charge-sensitive bed recordings were: motor-active waking 4 +/- 3%, active sleep 24 +/- 11%, intermediate sleep 22 +/- 8%, quiet sleep 47 +/- 13%, and undefined 4 +/- 2%. Positive answers to questions on civilian life sleepiness were related to high scores on scales for hypochondria, psychasthenia and sense of reality, and night sleep longer than 10 h to high scores for psychasthenia and sense of reality, but not to polygraphic measures. Two men with complaints about civil-time irresistible sleep at the time of beginning the military service had short Stage 2 latencies at the daytime minimum of alertness during service (4 and 8 min). Although alertness and sleep during military service were normal on average, the findings suggest that all conscripted individuals may not have had enough sleep.


"Numb, clumsy hands" and tactile agnosia secondary to high cervical spondylotic myelopathy: a clinical and electrophysiological correlation. Four patients presented with a distinctive syndrome of "numb, clumsy hand" and tactile agnosia. Myelography and computed tomographic myelography (CTM) of the cervical spine documented major spondylotic compressive lesions mainly between the C3 and C5 levels. The cortical responses of dermatomal somatosensory evoked potentials (DSEPs) revealed progressively prolonged peak latencies and progressively decreased amplitudes of early components from C6 to C8 dermatomal stimulation. In comparison, the C5 and L2 DSEPs were affected to a lesser extent. This finding suggests that high cervical cord compression may produce dysfunction of the dorsal column caudal to the direct compressive sites. In other words, the funiculus cuneatus of C6-8 cord is most affected in high cervical myelopathy. Moreover, the funiculus cuneatus is within the border zone susceptible to an overall reduction in blood flow. We conclude therefore, that ischemia secondary to cord compression is the pathophysiology resulting in this unique syndrome of "numb, clumsy hands" and tactile agnosia.


Neuropsychological abnormalities in patients with pituitary tumours. Neuropsychological assessment of 65 patients with pituitary tumours revealed impairment of memory and executive function. This did not appear to be related to the size or type of tumour or the effects of radiotherapy or surgery. It is possible that the problems arose from multiple unconnected factors but this observation lends support to the suggestion that pituitary or hypothalamic hormones have a role in the modulation of memory and behavioural pathways. Whatever the cause, neuropsychological impairment is common in patients with pituitary tumours and is an aspect of their disability which has received insufficient attention in the past.


Hypothermia, Wernicke encephalopathy and multiple sclerosis. Neurological exacerbation observed in MS patients is usually related to a demyelinating process. We report two patients where hypothermia (32.4 degrees C and 32.5 degrees C) and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). The clinical features and the rapid efficiency of parenteral thiamine were suggestive of WE. Hypothermia is an exceptional symptom observed in MS and has been considered as resulting from hypothalamic demyelination; these two cases showed that WE which is another cause of reversible hypothermia, can be associated with MS.


Vibratory perception thresholds in the female genital region. Vibratory perception thresholds (VPT) were determined in the hands, feet and genital region by means of an electromagnetic vibrator and expressed in terms of amplitude of stimulator movements measured by an accelerometer. Eight healthy women volunteers aged 27-44 were examined on 8-11 occasions each during the menstrual cycle. Ninety-five further women, aged 35-45 were consecutively selected from the waiting list for hysterectomy for non-malignant disorders and examined on one occasion each. VPT measurements were correlated to menstrual phases and blood oestradiol values. In the healthy volunteer group the mean VPT for clitoris was 0.27 mu (SD 0.10, range 0.09-0.48), for hands 0.19 mu (SD 0.09, range 0.05-0.37) and feet 0.51 mu (SD 0.39, range 0.17-1.5). In none of the two groups were there any significant differences between the VPTs of the different phases of the menstrual cycles nor was there any significant correlation between VPT and serum oestradiol levels.


Facial nerve stimulation through Stensen's duct. We report on a new method of stimulating the facial nerve through Stensen's duct. Electrical resistance of the skin and subcutaneous tissue is one of the major problems of neurophysiological facial nerve testing. To overcome this disadvantage, the authors show that the facial nerve can be stimulated with far less current through Stensen's duct. The NET, ENoG, and antidromic facial nerve responses are recordable at less than a third of the current required for conventional percutaneous stimulation. It is our belief that nerve stimulation through Stensen's duct will be a new and useful method for assessing facial nerve dysfunction in the early stage of palsy.


Superoxide dismutase in middle ear fluid from children with secretory otitis media. Superoxide dismutase (SOD) constitutes an important enzymatic defense against the destructive biochemical events associated with inflammation. To examine the presence of SOD in the middle ear fluid (MEF) in secretory otitis media (SOM) the content of SOD was measured in the MEF from 66 children with SOM. The applied method was based on light emission associated with reduction of the chemiluminescence of luminol reacting with superoxide anions (O2-). From the inhibition exerted by the addition of standard SOD the concentration of SOD in the samples was extrapolated. The findings divided the MEF's into two significantly different groups: 48% with undetectable SOD, 52% with a SOD range of 200-12,000 ng/ml, median: 3,333 ng/ml, 95% confidence limits: 2,000-5,000 ng/ml (p < 0.0005). It is suggested that the concentration of superoxide dismutase in the middle ear may play an essential role for the outcome of secretory otitis media and the effect of insertion of ventilation tubes.


Developmental changes in nasal airflow patterns. Airflow through each nasal passage was measured every 10 min throughout a 5-h period in 48 subjects whose ages ranged from 3 to 17 years. The data were subjected to statistical techniques that characterize and quantify periodicities in a time series. Such analyses revealed that for the majority of children younger than 7 years of age, the airflow through the two nostrils changed either randomly (50%) or in parallel (31%). Between the ages of 7 and 10 years, however, the distribution of airflow patterns characteristic of adults emerged, such that the incidence of reciprocity increased to 63%, and the incidence of random and parallel patterns decreased to 31% and 6%, respectively. A similar distribution was evidenced in the 11- to 17-year-old subjects (56% reciprocal, 38% random, 6% parallel). Although the total airflow through the nose also increased with age, the increased inspiratory flow rates could not account for the developmental changes evidenced in airflow patterns.


Efficacy of a topical nasal decongestant in different formulations: the effect of viscosity. Factors affecting the absorption of drugs through the nasal mucosa are increasingly being studied. Dosage form factors, i.e. the viscosity of the excipients, have been claimed to be of importance for enhanced nasal absorption due to prolongation of contact time between drug and mucosa. In the present study, a comparison was made of the effect of a local nasal sympathomimetic when administered intranasally in formulations with different viscosities. Volunteers received the test drugs as nasal sprays in a randomized cross-over design by a rhinomanometric technique, the effect of the drug being recorded for up to 5 h after administration. No significant differences in effects were observed when the test formulations were compared.


Distribution of goblet cells in the rat nasal septum by use of quantitative histological technique. In this quantitative, histological study, both goblet cell number and distribution of secretory granules in normal septal mucosa of rats were examined by computer-based color image analysis combined with a new, simple whole-mount method. Our new method has proved to be a very useful and highly accurate means of examination. The count and size of the mucous area of goblet cells decreased toward the antero-posterior direction with the exception of the apical region of the septum. The regional difference characteristic of the goblet cell is noteworthy. The results are assumed to be closely related to both flow direction of mucous blanket and distribution of nasal gland orifices. Goblet cells are assumed to be controlled by some regulatory factor of the secretory system and to play an important role in nasal physiological mechanism.


A new autosomal dominant syndrome of idiopathic progressive vestibulo-cochlear dysfunction with middle-age onset. A kindred is described with progressive autosomal dominant vestibulo-cochlear dysfunction resulting in instability in the dark, head movement dependent oscillopsia and hearing loss. The first symptoms appeared in the 4th decade and progressed to vestibular areflexia, presumably in the 5th decade and to almost total deafness in the 6th-7th decade of life. The history was negative for other neurological, otological or infectious diseases, or the use of neuro-ototoxic drugs. The affected subjects showed remarkable compensation for the loss of vestibular function.


Selective resection of the semicircular canals of rabbits with preservation of hearing. The goal of this investigation was to develop a method of surgical removal of the semicircular canals of the rabbit without induction of auditory impairment. Four different surgical techniques were utilized: i) fenestration of the lateral semicircular canal; ii) fibrin glue perfusion of the canal following fenestration; iii) removal of the lateral semicircular canal by drilling after fenestration and fibrin glue perfusion, and iv) removal of all three canals after fenestration and fibrin gluing. Brainstem auditory potentials were recorded repeatedly for up to 3 months after operation and demonstrated preservation of hearing in all rabbits in the first group and in 78% of the second group. In the third group the potentials could be recorded in 67% of the animals and showed a 20 dB deterioration of hearing. After removal of all three semicircular canals residual hearing could be recorded in 50% of the rabbits. These animals regularly showed a 30-40 dB deterioration of hearing. A precise microsurgical technique using fibrin glue and bone chips for interruption of the peri- and endolymph flow proved crucial for hearing preservation.


Three-dimensional analysis of caloric nystagmus in the rhesus monkey. The aim of this study was to investigate whether caloric nystagmus contains response components that can be attributed to a stimulation of the vertical semicircular canals. Three dimensional eye movement recordings with a dual search coil technique revealed important horizontal, vertical and torsional nystagmus components following irrigation of the external ear canal with cold water in various head positions relative to gravity. Horizontal nystagmus components, i.e. lateral semicircular canal vectors, followed a cosine function of both the pitch and yaw angle of the head relative to gravity, confirming a mainly thermovective mechanism for stimulation of the horizontal canals. Vertical and torsional nystagmus components behaved differently following left and right ear irrigations. Right-left symmetrical vectors emerged only when the vertical and torsional components were transposed into vectors of single semicircular canal directions. The intensity of these vertical semicircular canal vectors as a function of the position of the corresponding canal relative to gravity, however, excludes important thermovective mechanisms acting at the vertical canals. It remains an open question whether these vertical canal vectors represent a non-thermovective caloric stimulation of vertical canal afferents.


Vestibular, central and gastral triggering of emesis. A study on individual susceptibility in rats. Using kaolin intake as a behavioral index of emesis in rats, we examined the relationship between susceptibility to motion sickness and to emesis induced by apomorphine or copper sulfate. Rats showed a wide variation in susceptibility to motion sickness. Significant positive correlations were found between susceptibility to motion sickness and to emesis induced by intraperitoneal administration of apomorphine and by oral administration of copper sulfate. Motion, apomorphine and copper sulfate induce emesis through different receptors, so these findings suggest that the sensitivity of a common locus of emesis, presumably the emetic center in the brain stem, is one determinant of individual differences in susceptibility to motion sickness.


The interaction of smoking and noise on temporary threshold shifts. Four separate experiments examined the effects of cigarette smoking on temporary threshold shifts (TTS) following noise exposure. One experiment compared smokers and non-smokers after the subjects had abstained from smoking for at least 6 h. A second experiment tested only smokers who smoked a cigarette just before noise exposure, during the noise exposure and in a control condition during which they did not smoke. A third experiment tested only non-smokers who were exposed to noise after chewing nicotine gum or after a control condition in which they rested without chewing the gum. A fourth experiment tested smokers and non-smokers in one condition which required them to smoke a cigarette just prior to noise exposure and in another condition which prevented them from smoking. The results indicate that smokers consistently evidence slightly smaller TTS than do non-smokers. Non-smokers evidenced significantly greater TTS at one frequency after they had chewed nicotine gum than when they had not. These results suggest that the smaller TTS associated with cigarette smoking is related to both the chronic and the acute effects of smoking and that these effects may be more attributable to carbon monoxide than to nicotine.


The effect of acute hypoxia on the latency of the human auditory brainstem evoked response. Recent studies have shown a decrease in the amplitude and an increase in the threshold of the cat's auditory brainstem evoked response (ABER) during severe hypoxia (PaO2 of 20 to 30 Torr). In this study we have examined the effects of euoxia (end tidal PO2 100 Torr) and mild hypoxia (end tidal PO2 of 45 to 50 Torr) on the latency of the ABER in 6 human subjects. Hypoxia resulted in a blood O2 saturation of between 75 to 85% and caused a significant prolongation of the latency of wave V of the ABER by 0.185 +/- 0.045 ms (Mean +/- S.D; p < 0.01). The prolongation of the ABER during severe hypoxia has previously been attributed to a change in peripheral sensitivity. Using the stimulus level/response latency relationship obtained for each subject under normal breathing conditions, the change in latency produced by mild hypoxia can be interpreted as a mean shift in auditory sensitivity of 5.1 +/- 3.4 dB. These results suggest that the auditory system is sensitive to much smaller changes in blood O2 saturation than previously thought.


Phoneme recognition by deaf individuals using the multichannel nucleus cochlear implant. Experiments have been carried out to determine which cues are used in phoneme identification by deaf individuals using a cochlear implant. Five deaf individuals with a Nucleus 22-channel cochlear implant were tested with open set speech audiometry in free field without lipreading. Speech material consisted of lists of Dutch words of the Consonant-Vowel-Consonant type (CVC-words). Word scores ranged from 0 to 22%, phoneme scores from 11 to 54%. For each subject the responses to the initial consonant, the vowel and the final consonant were entered into separate confusion matrices. Kruskal analysis, which provided a geometric representation of these confusions, showed that in the recognition of consonants the feature of voicing is all important. Vowels were identified on the basis of the frequencies of the first and second formants. In one subject the electrode array could only partially be inserted into the cochlea, leaving roughly half the second formant area of the electrode array outside the cochlea. For this subject vowel identification was based upon the first formant and vowel duration; there was no contribution of second formant information to vowel identification. Compressing the first and second formant frequency to the limited intracochlear array did not enhance transmission of second formant information and did not improve performance. The basic findings for consonant and vowel recognition could be explained by the speech coding strategy of the Nucleus speech processor in which voicing determines stimulus periodicity and formant frequencies determine channel selection. Kruskal analysis of phoneme confusions may aid in programming and evaluating the performance of the Nucleus cochlear implant.


Influence of genotype and age on acute acoustic trauma and recovery in CBA/Ca and C57BL/6J mice. Two inbred strains of mice, CBA/Ca (with a moderate auditory impairment starting late in life) and C57BL/6J (with a progressive auditory degeneration starting during young adulthood), were exposed to a 120 dB SPL broadband noise (2-7 kHz) for 5 min at the age of 1, 3, or 6 months. Compound and permanent threshold shifts (CTS and PTS) were determined by auditory brainstem response during the first day (CTS) and 1 month (PTS) after exposure. With increasing age, susceptibility to CTS at middle frequencies (8 and 12.5 kHz) decreased in CBA mice, yet was retained in C57 mice. C57 mice were more severely affected by CTS than age-matched CBA mice. Noise-induced CTS was positively correlated to pre-exposure thresholds in C57 mice and to PTS over all ages and strains. The amount of recovery from CTS to PTS was, however, independent of age and strain. There was only a 2% risk of classifying CBA mice as C57 mice by pre-exposure thresholds at high frequency, while there was about 40% risk by CTS. The results indicate that genetic predisposition can affect susceptibility to auditory degeneration and noise impairment in a systematic manner, allowing the identification of susceptible individuals by pre-exposure audiometric examination, especially at high frequencies.


Bone repair in the otic capsule of the rabbit. The repair of 1 mm drill hole lesions in rabbit long bones and otic capsules was studied in undecalcified sections. Following surgery, bone formation was monitored during 12 weeks by intravital sequential time labeling with bone-seeking fluorochromes. In diaphyseal bone, initial repair by trabecular woven bone was accompanied by a transient remodeling response in primary repair bone and the surrounding compacta. In comparison, capsular defects showed a slightly deficient initial repair by woven bone which, once formed, persisted unchanged with no subsequent osteonal remodeling. In the surrounding capsule, the remodeling response was subtle and its duration much shorter. Moreover, the centrifugal distribution of bone remodeling units around inner ear spaces was preserved, suggesting that capsular repair is affected by the same morphogenetic field that controls perilabyrinthine growth, modeling and remodeling. The significance of these findings is briefly discussed in relation to otosclerosis and cochlear implant strategies.


Glycocalyx heterogeneity in normal and hydropic cochleas of the guinea pig. The endo- and perilymphatic glycocalyx of the cochlear epithelia were investigated ultrastructurally in normal and hydropic cochleas using the electron-dense markers cationized ferritin and colloidal thorium. In the normal cochleas all epithelial surfaces showed reactivity with both markers. Using cationized ferritin, no regional differences in reactivity could be demonstrated. With colloidal thorium, however, the apical membranes of the outer hair cells reacted more intensely than either the basolateral membranes or the membranes of the supporting cells of the organ of Corti. Cationized ferritin reactivity was not affected by digestion with either neuraminidase or hyaluronidase. In contrast, colloidal thorium reactivity of the endolymphatic surfaces was greatly reduced after neuraminidase digestion. Reactivity of the cell membranes lining the perilymphatic compartments of the cochlea was less affected by neuraminidase digestion, except for the basolateral membranes of the sensory and supporting cells of the organ of Corti, which demonstrated a greatly reduced reactivity. These findings indicate that the glycocalyx of the epithelial surfaces lining the endolymphatic compartment has a high content of sialic acid. The differences that are observed in normal cochleas in regard to colloidal thorium reactivity between the apical membranes of the outer hair cells and the membranes of the Deiters' cells, could not be demonstrated in hydropic cochleas. This probably contributes to the early functional changes in outer hair cells observed in experimental hydrops.


Axo-somatic contacts in the postnatal developing white rat spiral ganglion. Development of the spiral ganglion in white rats was followed during the first 2 weeks after birth and morphological characteristics of the two neuronal types (I and II) were examined. In some neurons different stages of partial degeneration leading to formation of residual bodies were found without observation of degenerated cell, supporting the idea that differentiation at this time is not associated with cell death. Contacts between cell body of type II neurons and neuronal endings is reported for the first time. Such axo-somatic contacts previously observed only in monkey and man, also exists in lower mammals.


The effect of batroxobin on cochlear blood flow. Cochlear blood flow is considered to be closely related to cochlear function. Among several etiologic factors implicated in inner ear diseases, disturbance of local blood flow is held to be one of the most important. With this in view, various pharmaceuticals are currently being used to increase local blood flow in patients with inner ear diseases. In the control of blood flow there are three major factors; systemic blood pressure (perfusion pressure), vascular tone, and blood viscosity. Batroxobin (BX) was developed to increase local blood flow by lowering blood viscosity through defibrinogenation; it is used in the treatment of thrombosis and occasionally for the treatment of sudden deafness. In the present study, we observed the effect of BX on cochlear blood flow in guinea pigs, using a laser Doppler flowmeter, and measured the blood fibrinogen concentration after BX infusion. There was an obvious increase in cochlear blood flow during the observation period of 3 h after 10 BU/kg were infused, and a slight increase when 2 BU/kg were infused. Blood fibrinogen levels decreased dramatically by 30 min after BX infusion (10 BU/kg), and the extremely low level attained was maintained throughout the 3-h observation period. Hemorrhage from the surgically opened ear was noted in 2 animals during the experiment and rectal bleeding in one.


Altered distribution of motor neurons in experimental facial nerve paralysis. The alteration of motor neurons in the brainstem after recovery from experimental facial nerve paralysis was examined by the retrograde horseradish peroxidase (HRP) technique in the rabbit. Six months after nerve crush injury at the center of the vertical portion, HRP was injected into the zygomatic muscle on the recovered side. The distribution of labelled neurons in the brainstem was compared with that in the normal rabbit. In control animals, motor neurons in the facial nucleus were somatotopically organized, and there were no labelled neurons in other nuclei in the brainstem. In recovered animals, on the contrary, the somatotopic organization of the facial nucleus was obscure and multipolar neurons of varying size were labelled bilaterally in the reticular formation from the pons to the medulla.


[Pharmacokinetics and pharmacodynamics of matrine and oxymatrine]. On measuring the percentage of QTc interval prolongation, the pharmacokinetic and pharmacodynamic profiles of i.v. matrine or oxymatrine in rabbits were analyzed by combined pharmacokinetic and pharmacodynamic model. The plasma concentration--time profiles of the two drugs can be described by a two--compartment open model, and the relationship between effect and effect compartment concentration of both drugs can be represented by the sigmoid Emax model. Marked differences in pharmacokinetic and pharmacodynamic parameters between the two drugs were found, but their pharmacokinetic and pharmacodynamic properties were dose--independent in the dose ranges used in the experiment.


[Cytochrome P450 monooxygenase contents and activities in human liver microsomes prepared from Chinese adults]. Seven human liver samples were collected in this study. Five of them were obtained from donors died from non-disease accident, one was taken from part of the normal tissue of a liver specimen obtained by partial hepatectomy in a case of hepatic cavernous hemangioma and the last one from postmortem died by road accident. All the liver pieces were stored at -75 degrees C immediately after removed from the body. Liver microsomes was prepared by differential ultracentrifugation. The contents of cytochrome P450 and cytochrome b5 in Chinese adult liver microsomes were 0.36 +/- 0.08 and 0.23 +/- 0.05 nmol.mg-1 protein (n = 7). The activities of aminopyrine and ethylmorphine N-demethylase, 7-ethoxycoumarin-O-deethylase, nifedipine oxidase and (-)-praziquantel hydroxylase were 1.07 +/- 0.23, 1.82 +/- 0.31, 0.30 +/- 0.10, 0.43 +/- 0.18 and 0.69 +/- 0.43 nmol.mg-1.min-1 (n = 7), respectively.


[Studies on the synthesis of dimethyl 4-hydroxy-4'-methoxy-5,6,5',6'-bismethylenedioxy biphenyl-2,2'-dicarboxylate--an essential metabolite of biphenyl diester]. This paper reports the synthesis of dimethyl 4-hydroxy-4'-methoxy-5,6,5',6'-bismethylenedioxybiphenyl-2,2'-dica rboxylate (II). Various conditions for bromination were tried to find the best one for synthesis of the key intermediate compound 6. After Ullmann condensation of 6 with 8 and hydrogenolysis, the title compound II was obtained. It was proved to be identical with the isolated metabolite of biphenyl diester by spectral data.


[Studies on the chemical constituents of Cynanchum thesioides]. Fourteen constituents were isolated from Cynanchum thesioides (Freyn) K. Schum. On the basis of chemical and spectral data, seven of them have been identified including two new compounds: glyceride-1,3-dipalmito-2-sorbate (4), and thesoideaside (7); and five known compounds: beta-amyrin acetate (I), lupeol acetate (2), alpha-amyrin caprylate (3), tamarixetin (5) and tamarixetin-3-O-beta-D-galacto-pyranoside (6).


[C21 steroidal constituents from Cynanchum hancockianum]. Two new compounds hancogenin B (V) and hancoside A (VI) and four known compounds glucogenin C (I), cynatratoside A (II), glaucogenin A (III) and anhydrohirundigenin (IV) were isolated from the roots of Cynanchum hancockianum (Maxim) Al. Iljinski. Their structures were identified on the basis of spectral evidence. The fragmentation ways of 13:14, 14:15-secopregnenes in EIMS were outlined and the antitumor activity of II and the antiendotoxic activity of VI were also preliminarily tested in vitro.


[HPLC analysis of the active ingredients of Forsythia suspensa]. Forsythia suspensa is a widely used traditional Chinese herb. Because of the need to evaluate its quality, a HPLC method was developed to analyze the active ingredients in its fruits and leaves. One g of powdered plant material was cold macerated over-night with 10 ml of methanol added then supersonic extracted for 20 min. Four ml of the extract were mixed with 1 ml of water, centrifuged (400 x g, 15 min), and then analyzed by HPLC with a Nucleosil C--18 column. The mobile phase for gradient elusion consisted of MeOH(containing 1% tetrahydrofuran) and H2O (containing 0.01 mol/L KH2PO4,pH 3.2) and monitored by UV absorption at 280 nm. The identity and purity of the peaks were checked by photodiode array detector and in comparison with standards. By this procedure, the active constituents caffeic acid, rutin, forsythoside A, forsythin, and forsythigenin were separated successfully, and the quantity of each compound was determined by peak area. Some fruit samples obtained from various sources and the leaf sample made as tea were analyzed by this method.


[Study of the polymorph of etoposidum].

[Study of the polymorph of etoposidum]. Etoposidum: 4'-demethyl-epipodophyllotoxin-beta-D-ethylidene-pyrano-glucoside or VP-16-213 in trade name is a semisynthetic antineoplastic drug. We found that it has two different kinds of crystal form named crystal A and B, they were crystallized from methanol and ethanol respectively. Their structures were identified by NMR and MS. They have similar infrared spectrum but with repeatable small differences. The powder X-ray diffraction pattern of the two kinds of crystals are quite different. The DSC curve of crystal A is rather smooth but that of crystal B shows abnormal positive and negative peaks. On the other hand, they have the same kind of smooth TGA curves. This fact shows that the positive and negative peaks are not the result of chemical reaction. After heating crystal B in DSC oven at 190 degrees C and 250 degrees C, respectively, their IR spectra showed that the pattern of the first one did not change, but the second one changed to the spectrum of crystal A. This reveals that the positive peak is due to the melting of crystal B and the negative peak is the result of the formation of crystal A. The pharmaceutic preparation of VP-16-213 is its glycerine solution, so the crystal form does not influence the efficacy of the drug.


[Determination of captopril in plasma and urine by high-performance liquid chromatography with column switching]. A rapid and sensitive column-switching high performance liquid chromatographic procedures was described for determination of captopril in plasma and urine. p-Bromophenacyl bromide, a derivatizing reagent, was added to the plasma and urine samples to form an adduct which showed ultraviolet absorbing properties. After that, the urine sample was injected directly and for plasma the protein was removed with 6% of perchloride before injection. The column-switching system was equipped with a pre-column of 5 cm x 0.5 cm ID, packed with mu Boundapak C18, 37-50 microns, and an analytical column of 15 cm x 0.5 cm ID, packed with YWG-C18, 10 microns. After washing out the impures from pre-column with 0.2% acetic acid the retained substances were eluted into analytical column with acetonitrile-water-acetic acid (35:65:0.4). Captopril was detected at 260 nm. The method was linear within 20-1000 ng/ml for plasma and 10-200 micrograms/ml for urine. The recovery averaged 103.2% and 99.5% for plasma and urine, respectively. The coefficient variations were all less than 10%.


[Study on the interaction between water-soluble vitamins by the "three-point-test" of differential scanning calorimetry]. The physico-chemical compatibility of solid-state pharmaceuticals is mainly determined by their interaction. The "Three-point-test" of differential scanning calorimetry in which three samples of different ratios are determined is proposed to study this interaction, and the simplified judging rules are as follows: If there are two or less than two endotherm peaks in DSC thermogram for all 3 ratio samples, we may mainly consider the peaks at lower temperature. If these temperatures are the same, which would be monotectic system or simple eutectic mixture, there will be very weak interaction in their solid state, and these could be compatible. If the temperatures are different, which would be solid solution system or solid complex system, there would be interaction in their solid state. If there is no endotherm peak, or there are exotherm peaks or there are more than two endotherm peaks, they all indicate that there is a stronger interaction in their solid state and they are incompatible. As an example, the interaction between water-soluble vitamins--Vit B1, Vit B2, Vit C and nicotinamide was determined. The results indicated that only Vit C is incompatible with nicotinamide, as there is a stronger interaction, and with Vit B1, there is a weak interaction.


[The photodegradation-assay method of sodium nitroprusside and its application to studies on percutaneous absorption]. A new method of quantitative analysis of sodium nitroprusside (SNP) was developed according to the principle of a photodegradation analytical method that has been reported by the authors previously. After irradiated of solution of SNP under fluorescent lamp, the increase in absorbance at 394 nm belonged to nonlinear kinetics, but the absorbance increment with concentration was linear in certain concentration range of SNP. When irradiated for 30 min or 60 min, SNP in solution can be quantitated accurately by delta A394. The standard curve of this method was linear from 50 to 1000 mg/L. The within-day and day-to-day precisions (RSD) were 1.9% and 2.6% respectively, with recoveries of 99.0-100.1%. No interference from small amount of serum protein, stearyl alcohol, propylene glycol, azone, m-nifedipine, nitrendipine and verapamil was observed. This method has been successfully applied to study percutaneous absorption.


[Study on the synthesis of N-hydroxymethyl-nicotinamide]. N-Hydroxymethyl-nicotinamide, an antimicrobic agent was prepared in good yield by treating nicotinamide with excess of formaldehyde in the presence of potassium carbonate. The condensation reaction was studied under different conditions, changing the amount of formaldehyde, with different kinds of bases and reaction time. The yield was 72.4% when the reaction was carried out using 3.0 g of nicotinamide, 5.0 ml of formaldehyde (36.8% aq. solution) and 0.03 g of potassium carbonate in boiling water bath for one hour. More than 5.0 ml of formaldehyde did not contribute to higher yield. The results showed that potassium carbonate was better than other bases, and one hour of reaction time was enough.


[Synthesis and radiosensitizing activity of nitro-arylimino-diethyl-sodium thiosulfate and nitro phenylalanine derivatives]. A series of compounds was synthesized, these compounds were tested for Hela-S3 cells in vitro for radiosensitizing activity. Five of them are 2,2'-(arylimino)-diethyl-sodium thiosulfate and two of them are phenylalanine derivatives. Most of them showed various degrees of radiosensitizing activity. Among them, SER of L07 was 1.89 at 3 mmol, and had low cytotoxicity to Hela-S3 cells, ID50 was 18.8 mmol. The relationship between radiosensitizing effects and chemical structure was discussed. It offers a base for further exploration of selectively hypoxic cell radiosensitizers.


[Quantitative analysis of tripchlorolide in pharmaceutical preparation by RP-HPLC]. A reversed phase high performance liquid chromatographic method for the assay of tripchlorolide (T4) in pharmaceutical preparation was developed. The method used a Nucleosil 5 C18 column and a mobile phase of methanol-water (1:1). The column effluent was monitored at 218 nm. T4, triptolide (T0) and 1,4-dimethoxybenzene (IS) could be separated in less than 25 min. The retention times of T0, T4 and IS are 11, 17 and 23 min respectively. The method is very simple and rapid.


Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle. A mixture of the three branched-chain amino acids (BCAAs) was supplied to subjects during two types of sustained intense exercise, a 30 km cross-country race and a full marathon, and the effect on plasma and muscle concentrations of aromatic and BCAAs was studied. When BCAAs (7.5-12 g) were taken during exercise, the plasma and muscle (vastus lateralis) concentration of these amino acids increased, while in the placebo groups the concentration of BCAAs decreased in the plasma and remained unchanged in the muscle. In the placebo group, both types of exercise caused a 20-40% increase in the muscle concentration of the aromatic amino acids, tyrosine and phenylalanine, and the plasma concentration of these amino acids was increased after the marathon. Since tyrosine and phenylalanine are neither taken up nor metabolized by skeletal muscle, the increases in their concentrations in muscle might indicate net protein degradation during exercise. However, when the subjects were supplied with BCAAs during exercise, the increases in tyrosine and phenylalanine concentrations in both muscle and plasma were prevented. These results suggest that an intake of BCAAs during exercise can prevent or decrease the net rate of protein degradation caused by heavy exercise.


Mechanisms in man for rapid refill of the circulatory system in hypovolaemia. Compensatory, net fluid transfer across the capillaries was studied in the arm of man with plethysmographic technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). Thirty, 60, and 110 cmH2O LBNP evoked rapid transfer of fluid from tissue to blood at average rates of 0.053, 0.088 and 0.147 ml min-1 100 ml-1 soft tissue, i.e. graded responses typical for a true homeostatic regulation. Other experiments demonstrated a net fluid absorption not only from the arm but also from a wide range of skeletal muscle and skin regions in the body during experimental hypovolaemia, i.e. the more or less generalized response required if the absorption process is to contribute importantly to plasma volume regulation. In a third series of experiments it was shown that gradually applied LBNP was a much less efficient stimulus for fluid gain into the circulation than rapidly instituted LBNP, tentatively explaining the fairly slow plasma volume refill in main in previous literature after experimental, true and necessarily slow blood loss. Taken together, the findings described warrant the conclusion that the described process of fluid gain into the circulation may be a very important component in the overall homeostatic circulatory regulation in states of hypovolaemia. The data in fact suggest that the process might be capable of increasing plasma volume by as much as 600 ml within only 10 min, suggesting that such plasma volume control might be much more potent than previously believed.


Expression of hsp70 gene in lymphocytes from normotensive and hypertensive humans. The impact of environmental factors on hypertension depends to a certain extent on the individual's genetic background. Environmental temperature is one of the known modulators of blood pressure. We have previously demonstrated abnormal expression of a major environmentally-controlled gene, hsp70, in hypertensive mice and rats. We have developed a simple ex vivo method for the evaluation of hsp genes expression in humans. In the present study, we investigated the accumulation of hsp70 mRNA in lymphocytes from normotensive and hypertensive humans. The data showed a higher accumulation of hsp70 mRNA in lymphocytes from hypertensives vs normotensives (2.04 +/- 0.35 vs 1.48 +/- 0.29 OD mm2, P < 0.05) submitted to heat stress (15 min at 42 degrees C). Basal levels were the same in both groups (0.11 +/- 0.01 vs 0.10 +/- 0.01 OD mm2, respectively). These results support our hypothesis that alterations in the expression of a major environmentally-controlled gene, hsp70, may be involved in enhanced environmental responses even in human hypertension.